May 11, 2015
Agenus issued results of a phase III study of
GlaxoSmithKline’s malaria vaccine candidate
RTS,S. The trial, launched in 2009 and concluded
in January 2014, enrolled 15,459 toddlers
(5-17 months) and infants (6-12 weeks). RTS,S
reduced the number of cases of clinical malaria
in young children (5-17 months at first vaccination)
by 36%, and in infants (6-12 weeks)
by 26% over an average follow-up period of 48
months. This resulted in an average reduction
of 1,774 cases of clinical malaria for every 1,000
children vaccinated (5-17 months), and an average
reduction of 983 cases of clinical malaria for
every 1,000 infants vaccinated over an average
36-month follow up. Children receiving the
vaccine candidate but not a booster dose had
lower rates of protection. The study showed
RTS,S averted even more cases of malaria in
areas with higher transmission rates. RTS,S trial
data were submitted to the EMA in June 2014
for review by CHMP. A positive opinion from
CHMP, together with a potential policy recommendation
from the World Health Organization
(anticipated by the end of 2015), would be the
basis for licensure applications to the National
Regulatory Authorities (NRAs) in sub-Saharan
August 25, 2014
Sanofi Pasteur reported results from a
large-scale, multi-center efficacy trial, which
found that Fluzone High-Dose (Influenza
Vaccine) was more efficacious in preventing
influenza in adults 65 years of age and older
compared to standard-dose Fluzone vaccine.
Investigators compared the vaccine’s efficacy in
a randomized, double-blind trial that spanned
two influenza seasons. The trial enrolled nearly
32,000 participants; 14,500 and 17,489 adults
65 years of age and older during the 2011-
2012 and 2012-2013 influenza seasons, respectively,
from 126 research centers in the U.S. and
Canada. 228 people in the Fluzone High-Dose
vaccine group (1.43%) and 301 people in the
standard-dose Fluzone vaccine group (1.88%)
had laboratory-confirmed influenza, demonstrating
Fluzone High-Dose vaccine was 24.2%
(95% CI, 9.7 to 36.5) more effective in preventing
influenza than standard-dose Fluzone
vaccine. Additionally, researchers determined
most rates for pneumonia, cardio-respiratory
conditions, hospitalizations, non-routine
medical office visits and medication use were
lower for the Fluzone High-Dose vaccine group
compared to the standard-dose Fluzone vaccine
group. These results formed the basis of
an FDA regulatory submission late last year to
seek a modification to the prescribing information
for Fluzone High-Dose vaccine reflecting
the improved efficacy compared to standarddose
Fluzone vaccine in adults 65 years of age
and older. Sanofi Pasteur anticipates a decision
later this year.
August 12, 2013
Novavax released results of a phase I trial of its respiratory syncytial virus (RSV) vaccine candidate in 220 healthy elderly adults (age 60 or older, with a mean age of 68). All subject groups receiving the recombinant fusion (F) protein nanoparticle vaccine candidate exhibited antibody responses against RSV at 28 and 56 days post-immunization, with risesin serum anti-F immunoglobulin G (IgG) antibody levels. Subjects received either 60μg or 90μg of the RSV F vaccine candidate, with or without adjuvant, or a placebo. The overall immune responses were greater in the groups receiving the 90μg dose of RSV F vaccine compared to the groups dosed with 60μg. The 90μg RSV F adjuvanted vaccine group experienced a 5.6-fold rise in anti-F IgG and a sero-response rate of 79% at day 56. Subjects receiving 90μg RSV F vaccine with adjuvant reached levels of competitive antibodies equivalent to 186μg/mL of palivizumab. Levels of antibodies specific for the antigenic site II peptide, representing the neutralizing epitope on the RSV F protein recognized by palivizumab, rose 5.6- to 12.5-fold, with best responses again in the 90μg RSV F adjuvanted vaccine group.
August 27, 2012
Biota and Daiichi Sankyo released results from a phase III trial of Inavir for the prevention of influenza. This multi-center, placebo-controlled, double-blinded study enrolled 1,500 patients within a family with a confirmed sufferer of influenza A or B. Contracted influenza was defined by an elevated body temperature, a positive measure of influenza virus in a PCR diagnostic assay and the display of at least two of the following symptoms: headache, muscle or joint pain, fatigue, chill or perspiration, nasal discharge, sore throat or cough. Results demonstrated that, compared to placebo, Inavir significantly reduced the proportion of patients contracting either strain of influenza in the household (p<0.0001). Furthermore, Inavir produced protective efficacies in excess of 70%. The drug was well tolerated. Based on these data, Daiichi Sankyo intends to apply for approval to market Inavir for the prevention of influenza before the end of 2012.
March 19, 2012
Inovio Pharmaceuticals issued results from a phase I trial of PENNVAX-B, a vaccine for the treatment HIV subtype B, prevalent in North America and Europe. This open label trial, HIV-001, enrolled 12 adult HIV-positive subjects who received a four dose series (day 0, weeks 4, 8 and 16) of PENNVAX-B containing 3 mg of DNA/dose via intramuscular electroporation. All subjects completed the four dose vaccination regimen. Significant vaccine-specific T-cell responses against at least one of the three vaccine antigens (gag. pol, or env) were observed in 75% of subjects following vaccination. Fifty percent of the subjects had strong vaccine induced antigen-specific responses above the pre-vaccination levels to at least two of the antigens. The responses induced by vaccination were predominantly antigen-specific CD8+ T-cells. There were no significant adverse events or vaccine related grade 3 or 4 adverse events and the vaccine was generally well tolerated.
March 12, 2012
Circassia reported results from a phase II trial of their ToleroMune T-cell vaccine against ragweed allergy. This randomized, double-blind, placebo-controlled trial enrolled 275 subjects with confirmed ragweed allergy in Canada. The subjects received one of four regimens of ToleroMune treatment over a three-month period. They were exposed to ragweed allergens in a validated exposure chamber and nasal and ocular symptoms were compared against the pre-treatment baseline. The T-cell vaccine's optimal regimen substantially reduced symptoms, achieving a 97% greater reduction than placebo (p≤0.05) in subjects who had a moderate level of symptoms at baseline. The treatment was safe and well tolerated in all groups.
March 5, 2012
BioSante issued results from a phase Ib trial of GVAX Pancreas cancer vaccine. This trial enrolled 30 subjects with previously treated, locally advanced or metastatic pancreatic adenocarcinoma who received GVAX plus ipilimumab (Yervoy) or ipilimumab alone. The addition of GVAX Pancreas cancer vaccine to ipilimumab increased the median survival from 3.3 months for the monotherapy to 5.5 months for the combination therapy, an increase of over 60%. The combination also demonstrated an increase in one year survival, from 7% to 27%.
January 30, 2012
Advaxis reported interim results from a phase II trial of ADXS-HPV, an immunotherapy for cervical cancer. Data are from 87 women with recurrent/refractory cervical cancer who have failed cytotoxic therapy. The subjects received ADXS-HPV (1x109 cfu) with and without cisplatin (40 mg/m2). The primary endpoint is overall survival. At six months, the percentage of women alive was 62%; at nine months 41% and at one year 40%. Clinical responses were observed in both treatment arms, with three complete responses and four partial responses. ADXS-HPV drug-related adverse events were reported by 34% of subjects. The majority of the events were transient and responded to symptomatic treatment, or resolved on their own. The trial is being conducted at 17 sites in India.
Dynport Vaccine Company issued results from a phase II trial of their recombinant botulinum vaccine candidate, rBV A/B. This double-blind, placebo-controlled trial enrolled 440 healthy adults who received two dosing schedules of the vaccine or placebo administered intramuscularly at 0, 28 and 182 days or 0, 56 and 182 days. Safety and immunogenicity were evaluated for an observation period of 18 months. The vaccine was safe and well-tolerated, and elicited a strong immune response. The maximum immune responses to both botulism neurotoxin serotypes were observed 28 days after the third dose. More than 94% of the subjects maintained detectable neutralizing antibody concentrations for at least one year after the third dose. The 0, 28 and 182-day schedule produced the strongest immune response and was selected for in an upcoming phase III trial.
October 24, 2011
GlaxoSmithKline reported results from a phase III trial of their malaria vaccine, RTS, S. This trial enrolled 15,460 pediatric subjects across seven African countries, Burkina Faso, Gabon, Ghana, Kenya, Malawi, Mozambique and Tanzania. The subjects were placed in age cohorts: ages six to 12 weeks who were vaccinated as part of their regular schedule of infant immunizations and ages five to 17 months, who received three doses of the vaccine. Analysis of the combined age groups showed 35% efficacy over a follow-up period ranging between 0 and 22 months. In the five to 17 months cohort, the vaccine reduced the risk of clinical malaria and severe malaria by 56% and 47%, respectively, over a 12 month period after vaccination. The trial is ongoing.
October 3, 2011
Circassia reported results from a phase II trial of their ToleroMune grass pollen vaccine. This randomized, double-blind, placebo-controlled study enrolled 50 subjects with grass pollen allergy who received four doses from one of five different treatment regimes over a 12-week period. Five weeks later skin and eye responses to grass pollen were assessed. The results showed that the vaccine reduced allergic symptoms in the eye by up to 30% more than placebo. The vaccine also improved early and late skin reactions by up to 54% and 19%, respectively, compared to placebo. The safety profile was similar to placebo.
September 19, 2011
Inovio reported interim results from a phase I trial of PENNVAX-G, a global HIV vaccine. This randomized, open label trial, RV262, plans to enroll 92 healthy subjects in the U.S and Africa. This interim data are from the first cohort of 11 subjects who received a priming immunization with PENNVAX-G at months zero and one, followed by boosting with MVA-CMDR at months three and six. Data revealed a strong cell-mediated immune response, with CD4+ and CD8+ T cells specific for both the gag and env antigens encoded by the prime and boost agents. Anti-env CD4+ T-cell immune responses were noted in 100% (11 of 11) of evaluated subjects and CD8+ T-cell responses were noted in 45% of evaluated subjects after the first MVA boost following the two DNA vaccinations. The env specific CD4+ and CD8+ T-cell response rates were noted to be 73% and 45% respectively after the second MVA boost.
July 25, 2011
SEEK Biopharmaceuticals issued results from a phase Ib/II trial of HIV-v, their investigational prophylactic and therapeutic HIV vaccine. The trial enrolled 55 HIV-positive subjects who were placed in five groups: four vaccinated with the HIV-v vaccine and one placebo. The four vaccinated groups were divided into low-dose with and without adjuvant and a higher-dose with and without adjuvant. After a single injection there was a 90% reduction in the viral load of vaccinated subjects compared with placebo subjects.
February 28, 2011
Bellicum Pharmaceuticals issued results from a phase I/II trial of BP-101, a drug-activated dendritic cell vaccine for prostate cancer. This dose escalation study enrolled 12 subjects with metastatic castrate resistant prostate cancer. The subjects received BPX-101 in combination with activating agent AP1903, administered every other week for six doses. Responses were assessed at week 13. Treatment with BPX-101 and AP1903 resulted in RECIST Partial and Complete Responses in three of twelve (25%) subjects, including Complete Responses in subjects with visceral metastatic disease. Two of twelve (17%) subjects experienced PSA declines approaching 50% within the first 12 weeks of therapy. Both subjects experienced clinical, symptomatic improvement in conjunction with these PSA declines. Treatment with BPX-101 and AP1903 also elicited immunological responses in the majority of subjects evaluated. The combination of BPX-101 and AP1903 was safe and well tolerated at doses up to 25 million cells and 0.4 mg/kg respectively, at this dosing schedule.
February 7, 2011
Circassia released results from a phase II trial evaluating their ToleroMune T-cell vaccine for cat allergies. This Canadian-based, randomized, double blind study enrolled 202 subjects who received either four or eight standardized doses of ToleroMune treatment, or placebo. They were exposed to aerosolized cat dander in an environmental exposure chamber, both before and after treatment, to measure the effect of the ToleroMune T-cell vaccine. Results showed the ToleroMune vaccine had an immediate and growing treatment effect as allergen exposure increased. The subjects who received four doses of the vaccine over a period of 12 weeks had significantly reduced levels of allergy symptoms when compared with placebo (p≡0.05). These subjects experienced a 55% greater improvement in their symptoms. ToleroMune treatment was well tolerated, with a safety profile similar to placebo.
November 29, 2010
Celldex issued results from a phase II trial of rindopepimut, an immunotherapeutic vaccine under investigation for glioblastoma multiforme (GBM). This open label trial, ACT III, enrolled 65 subjects with newly-diagnosed EGFRvIII-expressing GBM who had undergone surgical resection followed by radiation therapy, temozolomide (TMZ) without tumor progression. Rindopepimut mixed with granulocyte-macrophage colony stimulating factor (GM-CSF) (~150 mcg) was administered intradermally bi-weekly for three doses prior to starting maintenance TMZ and monthly thereafter on day 21 of each TMZ cycle until disease progression. The results for the predefined primary endpoint (66% Progression Free Rate at approximately 8.5 months post-diagnosis) show a statistically significant improvement (p≡0.0168) over a predetermined estimate of 53%, which is beyond the range of expected progression-free survival for treatment with standard of care, consisting of radiation plus TMZ. In addition, 82% of the evaluable population developed a specific anti-EGFRvIII antibody response that was maintained at a significant level. Vaccination with rindopepimut plus TMZ was well tolerated.
November 22, 2010
Inovio Pharmaceuticals reported positive preliminary results from a phase I trial of PENNVAX-B, a DNA vaccine for the prevention of HIV clade B. This randomized, double blind, placebo controlled trial (HVTN 080) enrolled 48 healthy, uninfected subjects in the US. The subjects received a placebo, a 1 mg dose of PENNVAX-B vaccine, or a 1 mg dose of PENNVAX-B along with IL-12 DNA. The vaccine or placebo was administered with electroporation at months 0, 1, and 3. Preliminary data include safety data from all subjects and immunogenicity data from 38 out of 40 samples from vaccine recipients post-second-dose and from 31 out of 40 samples from vaccine recipients post-third-dose. After two vaccinations, 61% of evaluated subjects receiving PENNVAX-B showed either CD4+ or CD8+ or both T-cell responses against at least one of the vaccine antigens. After three vaccinations, 84% of evaluated subjects had positive T-cell responses. In addition, 67% (6 of 9) of evaluated subjects receiving PENNVAX-B and 91% (20 of 22) of evaluated subjects receiving PENNVAX-B + IL-12 were observed to have generated antigen-specific T-cell responses (either CD4+ or CD8+). Antigen-specific CD4+ T-cell responses were generated by the vaccine in 70% of evaluated subjects (21 out of 30) and strong antigen-specific, CD8+ T-cell responses were also generated by the vaccine in 55% of evaluated vaccine recipients (17 out of 31). The vaccine with or without IL-12 was generally safe and well tolerated.
October 26, 2009
NorthWest Biotherapeutics reported positive long-term follow-up from phase I/II trials of DCVax-Brain, a dendritic cell immunotherapy vaccine for Glioblastoma multiforme. Data are from 20 subjects who were administered three injections of DCVax-Brain intradermally two weeks apart. All subjects were also treated with current standard of care (surgical removal of the initial tumor, plus radiation and chemotherapy). At this time, 1 subject treated with DCVax-Brain in addition to standard of care had died. This subject had survived for approximately 7 years (80.5 months). Overall, 85% of the subjects treated with DCVax-Brain have lived longer than the median survival with the current standard of care treatment (14.6 months versus 36.4 months; p≡0.0004). In addition, 22% of the subjects treated with DCVax-Brain have reached or exceeded the 6-year survival mark. With standard of care treatment, less than 5% of patients with GBM are still alive at 5 years. Disease progression was also markedly improved with DCVax-Brain. With standard of care treatment alone, GBM brain tumors typically recur (progress) in 6.9 months while the median time to disease progression in the subjects treated with DCVax-Brain is 26.4 months (p≡0.00001). In the subjects treated with DCVax-Brain plus standard of care, 74% have been free of recurrence for 1 year, 45% recurrence-free for 2 years, 33% for 3 years, 28% for 4 years and 22% recurrence-free for 5 years.
September 7, 2009
Novavax reported positive results from a phase II trial of their seasonal influenza virus-like particle (VLP) vaccine candidate. This randomized, blinded, placebo-controlled study enrolled 221 healthy adult subjects between the ages of 18 to 49 years. The subjects receive a single injection of either a placebo or influenza vaccine at doses of 15 mcg or 60 mcg. The vaccine contained three VLPs (H3N2, H1N1, and B) that were matched to the strains recommended for influenza vaccines for the past flu season (2008-2009). An additional 20 subjects received Fluzone, a licensed, egg-based influenza vaccine. Novavax's influenza VLP vaccine candidate was well tolerated and no vaccine-related serious adverse events were reported. The VLP vaccine also induced strong hemagglutination inhibition (HAI) antibody responses against the influenza H1N1, H3N2, and B strains. Seroconversion rates (percentage of subjects with a 4-fold or higher rise in HAI titer from baseline) ranged from 81-86% for H3N2, 57-66% for H1N1, and 62-67% for B for subjects with and without existing antibody before vaccination. The subjects who received Novavax's VLP vaccine had higher antibody responses against the H3N2 virus that was circulating in the community than recipients of Fluzone.
July 13, 2009
Vical reported positive interim results from a phase II trial of TransVax, a vaccine for the treatment of cytomegalovirus (CMV). This two-arm, double-blind, placebo-controlled multi-center study enrolled 80 donor/recipient stem-cell-transplant patient pairs across sites in the US. In one arm, vaccine or placebo was administered to both the donors and recipients (the donor-recipient arm). In the other arm vaccine or placebo was administered only to the stem cell transplant recipients (the recipient-only arm). The trial was designed to evaluate the potential of TransVax to prevent CMV reactivation in immunosuppressed CMV-seropositive hematopoietic stem cell transplant (HCT) recipients. Data are from a four month analysis. At the four-month time-point, TransVax demonstrated a clear reduction compared with placebo in the percentage of recipients experiencing CMV reactivation. TransVax also showed a decrease in recurrence of CMV reactivation, a delay in time to initial detectable viremia, a decrease in duration of viremia, and decreases in peak and cumulative viral loads. An overall increase in cellular immune responses compared with placebo was also observed.
October 6, 2008
Crucell and Sanofi Pasteur reported positive preliminary results from a phase II trial of CL-184, a vaccine for the treatment of rabies. This randomized, single-blind, controlled study enrolled 140 healthy subjects in the US. The subjects received CL-184, a currently marketed human rabies immune globulin (HRIG) or placebo plus rabies vaccine. The neutralizing activity against the rabies virus was comparable to that provided by the HRIG. By day 14, all subjects administered the monoclonal antibodies combination together with the rabies vaccine reached the level of 0.5 IU/ml, a neutralizing activity levels thought to provide protection. The development of the immune response to the rabies vaccine was comparable in the monoclonal antibody combination and the human rabies immune globulin groups. The vaccine was well tolerated; there were no serious adverse events reported and most adverse events were mild or moderate in severity.
September 29, 2008
Allergy Therapeutics reported positive data from a phase III trial of Pollinex Quattro for the treatment of ragweed allergy. This double-blind, placebo-controlled study, dubbed R301, enrolled 993 subjects in the US and Canada. The subjects received four injections of either Pollinex Quattro or placebo over three weeks prior to the 2007 ragweed pollen season. The primary endpoint was the difference in combined symptom plus medication score between active and placebo treatment over the four peak pollen weeks of the season. Of the 993 enrolled subjects, 381 received all four injections. The study met its primary endpoint, with Pollinex Quattro Ragweed demonstrating a statistically significant 12% benefit over placebo (p=0.0478). The vaccine was well tolerated. Based on the results, Allergy Therapeutics plans to move forward with the development of Pollinex Quattro.
August 18, 2008
ALK-Abello reported positive results from a phase II/III trial of their sublingual house dust mite allergy vaccine. This randomized, double-blind, placebo-controlled, parallel-assignment study enrolled 604 adolescent and adult subjects in Europe. The subjects were placed in four cohorts, the first three cohorts received the vaccine tablet in various doses and the fourth cohort received placebo. The primary endpoint was to determine whether subjects suffering from allergic asthma caused by house dust mite allergy can reduce their use of conventional asthma medicine in the form of inhaled steroids when treated with the tablet vaccine. The cohort who received the highest dose of the tablet vaccine achieved a 50% reduction (median value) in their use of inhaled steroids compared to baseline. This effect was highly statistically significant compared to placebo (p=0.0036). The tablet vaccine was well tolerated and had a good safety profile. Based on the results ALK-Abello plans to move forward with the development of the vaccine.
May 12, 2008
Novartis released positive results from a phase III trial of Menveo, a vaccine for the prevention of meningitis. This head to head study enrolled 2,100 subjects, aged eleven to eighteen years, who received a single vaccination with either Menveo or Menactra, an FDA approved vaccine. Data showed that the subjects who were immunized with Menveo generated higher levels of antibodies against four meningococcal serogroups: A, C, W-135 and Y. One month after vaccination geometric mean titers for Menveo versus Menactra were: serogroup A, 29 versus 18; serogroup C, 59 versus 47; serogroup W-135, 87 versus 44 and serogroup Y, 51 versus 18. The percentage of subjects who achieved a protective immune response, determined by a human serum bactericidal antibody titer (hSBA) > 1:8, with Menveo compared to Menactra was: serogroup A, 75% versus 67%; serogroup C, 84% versus 84%; serogroup W-135, 96% versus 88%; and serogroup Y, 88% versus 69%. In addition, among adolescents with low levels of immunity at the time of vaccination, 81% who received Menveo generated a protective immune response against serogroup Y versus 54% with Menactra. Based on positive phase results Novartis plans to submit a BLA to the FDA by the end of 2008.
April 7, 2008
Avant released positive results from a phase II trial of Ty800, a vaccine for the treatment of Typhoid Fever. This randomized, placebo-controlled, double-blind, dose-ranging trial enrolled one hundred and eighty three healthy, adult subjects in the United States. The subjects received Ty800 1x10(8) or 1x10(9) colony-forming units (CFUs) or placebo and were followed for six months post-vaccination. The primary endpoints were to determine the optimal dose of Ty800 for further development based on safety, reactogenicity, and immunogenicity. Immunogenic response was dose-dependent. Positive immune response or seroconversion (prospectively defined as a 4-fold increase in anti-LPS titers over pre-dose level) rates were 65.5% and 80% in the low and high dose groups, respectively, and was significantly higher than placebo (p less than 0.001). Ty800 was well tolerated, with the incidence of reactogenicity symptoms and adverse events post-vaccination similar to placebo. Based on the results, Avant plans to move the development of the vaccine forward.
March 31, 2008
Iomai reported positive interim results from a phase I/II trial of their influenza vaccine patch in combination with an injected H5N1 influenza vaccine. This study enrolled five hundred subjects who received an egg-derived H5N1 influenza vaccine, the adjuvant vaccine patch and placebo to determine which combinations would be most effective in a two-immunization regimen, administered twenty-one days apart. Of fifty subjects vaccinated a single time with a 45-microgram dose in combination with the Iomai patch, 92% had an immune response. Seventy-three percent of these subjects achieved an HI titer of greater than 40, a value which may eliminate the need for a second vaccination. Of the subjects who received the vaccine alone, without a patch, 49% had an immune response considered protective after the first dose. The difference between the patch and no-patch groups was statistically significant (p<0.0001). A second dose of both vaccine and patch further enhanced immunogenicity; 100% of subjects who received two 45-microgram doses of vaccine and two Iomai patches had a measurable immune response, and 94% of subjects had immune responses considered protective. Treatment was well tolerated, with no adverse events reported. Based on the results, Iomai will continue on with the trial as planned.
January 14, 2008
Novartis issued positive results from a phase II trial of Menveo, a vaccine for the treatment of meningococcal disease. This randomized, open-label trial enrolled four hundred and twenty one infants in the United Kingdom and Canada. The trial was designed to evaluate multiple schedules, including two three-dose primary schedules, at either two, three and four months and two, four and six months. Some of the infants received either an additional dose of Menveo or a plain meningococcal polysaccharide at twelve months. One month after the last primary immunization, the percentage of infants with human serum bactericidal antibody assay (hSBA) titers greater than or equal to 1:4 in the 2, 3, 4-month group was 93% or above for all four serogroups: A, C, W-135 and Y. Immunization at two, four and six months resulted in a similarly high percentage of infants achieving immune response for serogroups C, W-135 and Y, and 81% for serogroup A. The dose at twelve months generated a strong immune response across all four serogroups, was shown to increase levels of immunity, and is likely to provide sustained protection. Phase III trials of Menveo are currently underway.
Novavax reported positive interim results from a phase I trial of their VLP pandemic influenza vaccine. The initial stage of this study enrolled seventy healthy subjects, aged eighteen to forty years, who received two doses of either 15 or 45 mcg of the VLP vaccine candidate or a placebo. The primary endpoints were safety and immunogenicity, including hemagglutinin inhibition (HAI) and neutralizing antibody responses. The vaccine was well tolerated in all treatment arms. In the 45 mcg arm, 83% had neutralizing antibody against the H5N1 A/Indonesia/05/2005 avian flu strain after the second vaccination. A 4-fold rise in neutralizing antibody from baseline was observed in 63% of the subjects. In regard to HAI responses, 48% had a 4-fold increase in titer from baseline. All subjects tested negative for antibodies to the H5N1 Indonesia strain before vaccination and no responses were observed among individuals who received a placebo. The vaccine also induced responses against the A/Viet Nam/1203/2004 avian flu strain. In 15 mcg dose arm 75% of the subjects had neutralizing antibody against the Indonesia strain. Based on the results, the next stage of the trial has commenced whereby the safety and immunogenicity of vaccine doses up to 90 mcg will be assessed.
October 15, 2007
Emergent BioSolutions issued positive preliminary results from a phase II trial of their oral typhoid vaccine. This randomized, blinded, placebo-controlled, single-dose trial enrolled 151 pediatric subjects between the ages of 5 and 14 years in Vietnam. The vaccine was immunogenic, with an overall immune response rate of greater than 50%. In addition, the vaccine induced significantly higher antibody concentrations in the vaccine group compared to the placebo control group. Treatment was well tolerated with no reported serious adverse events and an adverse events profile similar to placebo. Based on the results Emergent BioSolutions plans to move forward with the development of their oral typhoid vaccine.
August 13, 2007
Iomai released positive results from a phase I trial of their TIM ETEC patch-based vaccine for the treatment of travelers' diarrhea caused by enterotoxigenic Escherichia coli. This safety and immunogenicity trial enrolled 19 elderly subjects and 17 young adult subjects, in Ireland. The subjects received two patches, 21 days apart, containing "heat labile" toxin, or LT, and were followed for 42 days. The trial was designed to compare the number of elderly subjects who seroconverted to the number of young adult subjects who seroconverted. Results showed that all subjects who received the Iomai patch, regardless of age, seroconverted with IgG antibodies. In addition, 18 of 19 elderly subjects and 15 of 17 adult subjects also seroconverted with IgA antibodies. The patch was well tolerated, with no treatment related adverse effects reported. Based on the results, Iomai plans to initiate phase III trials in 2008.
Roche released positive interim results from a phase IIIb trial of Invirase for the treatment of HIV. This randomized, open-label trial, dubbed GEMINI, enrolled 337 subjects internationally. Subjects received Invirase plus ritonavir or lopinavir plus ritonavir given at their approved twice-daily dosages in combination with two nucleoside reverse transcriptase inhibitors (NRTIs; emtricitabine/tenofovir), once daily. The primary endpoint was the number of subjects with an HIV-1 RNA viral load of less than 50 copies per mL of blood at week 48. Secondary endpoints included measurement of lipid safety parameters. Efficacy results at 24 weeks showed that 69.9% and 69% of subjects treated with Invirase/ritonavir and lopinavir/ritonavir, respectively, achieved undetectable HIV levels (less than 50 copies per mL of blood). The same proportion of subjects in both groups achieved undetectable of less 400 copies per mL of blood. The increases in CD4 counts were comparable in both groups, with a median increase from baseline of 127 cells per cubic mL of blood for those in the Invirase/r group, and 134 cells for subjects in the lopinavir/r group. In addition, at 24 weeks, subjects treated with Invirase/r showed a lower median increase in their total cholesterol (TC) and total triglycerides (TG) than subjects treated with lopinavir/r (increase of 17 versus 26 mg/dL for TC, and an increase of 14 versus 43 mg/dL for TG). Based on the results, Roche planned to continue with the study.
August 6, 2007
AlphaVax released positive results from a phase I trial of their influenza vaccine. This placebo-controlled, randomized, double-blind study enrolled 216 healthy subjects who received a single dose of the vaccine at one of two dose levels. Data was taken four weeks after vaccine administration. Protective HI serum antibody titers were observed in 77% of the low dose and 80% of the high dose cohorts who had pre-vaccination influenza serum antibody titers (measured by hemagglutination inhibition, or "HI") that were below levels deemed protective against influenza infection. Based on the results, AlphaVax plans to move forward with the development of their influenza vaccine.
Incyte announced positive results from a phase IIa trial of INCB9471 for the treatment of HIV. This placebo-controlled trial enrolled 23 treatment-naive or treatment-experienced HIV-infected subjects harboring R5-tropic virus. Subjects received INCB9471 200 mg once-daily or placebo for 14 days. Subjects receiving INCB9471 showed rapid and prolonged reduction in viral load with a mean maximal decline of 1.81 log10 at day 16. The viral load continued to be suppressed well beyond the 14-day dosing period, with a mean 0.81 log10 decline in viral load observed at day 28. CD4+ cell counts were stable or slightly increased over the 14 day treatment period. Based on the results, two phase IIb trials are planned for early 2008.
Pfizer reported positive results from a phase III trial of maraviroc for the treatment of HIV. This 48-week trial was dubbed MERIT (maraviroc versus Efavirenz Regimens as Initial Therapy) and enrolled CCR5-tropic HIV-1 infected subjects who had never received antiretroviral therapy and had no evidence of resistance to the drugs used in the study. MERIT was designed to compare maraviroc (300 mg twice daily) to efavirenz, standard of care, (600 mg once daily), both dosed in combination with zidovudine/lamivudine. In the full set analysis, the rates of virologic suppression were 70.6% and 73.1% for the maraviroc and efavirenz groups, respectively, for less than 400 copies/ml and 65.3% vs. 69.3%, respectively, at less than 50 copies/ml. Increases in CD4+ cell counts from baseline were also greater with maraviroc (+170 cells/mm3) than with efavirenz (+144 cells/mm3). In addition, fewer subjects in the maraviroc arm experienced Grade 3 or 4 adverse events compared to the efavirenz group. The FDA issued an approvable letter for maraviroc in June of 2007.
Schering-Plough issued positive long-term data from a phase II trial of vicriviroc for the treatment of HIV. This randomized, double blind study enrolled 118 HIV infected, treatment-experienced subjects. Treatment administration was vicriviroc (5, 10 and 15 mg) or placebo, in combination with an optimized ritonavir-boosted protease inhibitor-containing antiretroviral regimen, once daily. This data was from 48-weeks post-treatment. Subjects in the 10 mg and 15 mg vicriviroc treatment groups achieved a median decrease in viral load of 1.92 and 1.44 (log10 copies/mL) and a median increase in CD4 cell count of 130 and 96 (cell/uL) from baseline, respectively. Subjects in the vicriviroc groups had undetectable virus at 48 weeks (HIV-1 RNA <400/<50 copies/ml) compared to those in the placebo group and fewer subjects in the vicriviroc groups experienced virological failure compared to those in the placebo group (27% and 33% versus 86%, respectively). This randomized, double blind study enrolled 118 HIV infected, treatment-experienced subjects. Treatment administration in this trial was vicriviroc (5, 10 and 15 mg), or placebo, in combination with an optimized ritonavir-boosted protease inhibitor-containing antiretroviral regimen, once daily.
May 28, 2007
Avant released positive preliminary results from a phase I/II trial of Ty800, a vaccine for the prevention of Typhoid Fever. This double-blind, placebo-controlled, dose escalating trial enrolled 47 healthy subjects who were randomized to receive one of three doses of Ty800: 8x10(7), 6x10(8) and 1x10(10) colony-forming units (CFU) or placebo. Subjects were than followed for six months. The dose of 6x10(8) CFU appeared to be immunogenic with similar reactogenicity as placebo. In addition, over 90% of subjects receiving the vaccine showed positive immune responses for both systemic (IgG) and mucosal (IgA) antibodies to typhoid based on an ELISPOT assay. Based on the results, Avant plans to initiate a phase II trial by mid-2007.
March 12, 2007
Acambis reported positive results from a phase III trial of ChimeriVax-JE for the treatment of Japanese Encephalitis. This double-blind trial enrolled 820 subjects who were randomized 1:1 to receive the single dose ChimeriVax vaccine (preceded by two doses of placebo) or JE-Vax, a licensed three dose vaccine. The trial was designed to compare immunogenicity profiles of the two vaccines 30 days after administration. Treatment was safe and well tolerated with adverse events, including local site injection reactions, significantly lower in the ChimeriVax-JE group. The primary efficacy endpoint, non-inferiority in seroconversion rates based on neutralizing antibodies against the relevant homologous JE virus, was reached. Of the subjects in the ChimeriVax group, 99.1% seroconverted compared with 74.8% of those in the JE-VAX group. ChimeriVax-JE also elicited a rapid immune response, with 93.6% of those vaccinated generating neutralizing antibodies 14 days after vaccination. Acambis plans to move this product towards regulatory approval in 2007.
Iomai issued positive results from a phase II trial of their TIM ETEC vaccine patch for the treatment of traveler's diarrhea caused by enterotoxigenic Escherichia coli. This double-blind trial enrolled 27 subjects who were traveling to Mexico or Guatemala. Subjects received three doses of the vaccine or placebo and were then given a dose of E. coli larger than would be expected under natural conditions. Both groups met the definition of moderate to severe illness, however the group receiving the vaccine had significantly fewer loose stools (p=0.04) and lower mean weights of the loose stools (p<0.05). In addition, only 14% of the subjects in the vaccine group required intravenous fluids versus 40% in the placebo group. Also, an increase in antibodies associated with E. coli infection were observed in the vaccine group; 100% had a four-fold increase in serum IgG and 97% had a four-fold increase in IgA. Based on the data, Iomai plans to initiate phase III trials later in 2007.
March 5, 2007
Pfizer reported positive interim data from two phase III trials of maraviroc for the treatment of HIV. Both trials enrolled subjects with CCR5-tropic HIV-1 infection across several international sites. Subjects were randomized to receive maraviroc (once a day or twice a day) along with a background regimen of current HIV therapy or background therapy alone. Of the 601 subjects enrolled in the first study, 60.4% of those who took the twice daily combination treatment achieved a level of less than 400 HIV copies per milliliter of blood, compared to 54.7% on a once-daily dose and 31.4% on just background therapy. The second study enrolled 475 subjects. Results revealed that 61.3% of twice-daily maraviroc subjects achieved target HIV levels, compared with 55.5% on once-daily therapy and 23.1% treated only with background therapy. Full results from both of the trials are expected by the end of 2007.
February 26, 2007
The Immune Response Corporation released positive preliminary results from a phase II trial of Remunne and IR-103, first and second HIV vaccine candidates. This randomized, double-blind trial enrolled 55 subjects in Italy who received intramuscular injections of Remunne, IR103 (0.1 mg), IR103 (0.5 mg), IR103 (1.0 mg), or saline every 12 weeks for 54 weeks. The primary endpoint was HIV-specific immune response. CD4+ cell counts were measured at baseline and at weeks 4, 12, 24 and 36. Initial data revealed that the two treatments stabilized CD4+ T-cell counts when compared to placebo at weeks 24 and 36. No substantial difference in efficacy was seen between the Remunne and IR-103 groups and no impact on viral load was observed as compared to placebo. Further results are expected in mid-2007 and the trial is slated to conclude in 2008.
February 12, 2007
GeoVax issued positive preliminary results from two ongoing phase I trials of their DNA/MVA AIDS vaccine. The first trial enrolled 11 subjects, 9 of whom received the vaccine and 2 of whom received placebo. The subjects received 1/10 of the vaccine administered at week 0 and week 8 to prime the immune response which was boosted by the administration of another 1/10th dose of the vaccine at week 16 and again at week 24. Results revealed a good safety profile and positive immune response. The second trial has enrolled 36 subjects, 30 of whom received the vaccine at the full dose and six of whom received placebo. Preliminary results have shown an acceptable safety profile. Complete results are expected later in 2007. Pending positive results, a large scale phase II trial is planned for late 2007 or early 2008.
February 5, 2007
Crucell announced positive results from a phase I trial of a West Nile virus vaccine. This randomized, double-blind, placebo-controlled, dose-escalation trial enrolled 47 subjects in Belgium. Three different dosages of the vaccine were administered twice, with three weeks interval between each. The primary endpoint was the incidence of adverse events for a two month period following the first intra-muscular injection. Treatment was systemically and locally well tolerated. The most commonly reported adverse events included headache and injection site reactions. Based on the results, Crucell plans to move forward with the development of the vaccine.
Polydex announced negative preliminary results from a phase III trial of Ushercell for the treatment of HIV. This double-blind, randomized trial enrolled 2,574 women in South Africa, Benin, Uganda, and India. Half of the subjects received Ushercell and half received placebo. All subjects underwent HIV counseling. The primary endpoint was a significant decrease in HIV incidence among Ushercell users compared to placebo users. Preliminary results revealed that Ushercell led to an increased risk of HIV infection in women at some of the participating sites. At this time it was not determined why the use of this therapy was associated with increased HIV risk. Based on the data, this phase III trial was halted until results could be further examined.
October 23, 2006
Hollis-Eden reported positive results from a phase I/II trial of Neumune for the treatment of Acute Radiation Syndrome (ARS) and nosocomial infections. This double-blind, placebo controlled, multi-dose trial enrolled 18 subjects who were separated into two equal cohorts, one with an average age of 29.4 years and the other with an average age of 68.2 years. Each cohort received 200 mg of Neumune or placebo, administered via intramuscular injection, once per day for 5 days. Treatment was well tolerated in both cohorts, with the most commonly reported adverse event injection site reactions. Efficacy data revealed that bone marrow regeneration occurred; neutrophil and platelet levels were elevated from baseline through at least 28 days in Neumune-treated subjects in both cohorts. Statistical significance in the increase in neutrophil and platelet counts was reached for the Neumune-treated subjects when compared to the placebo-treated subjects at multiple time points in a pooled analysis of both cohorts. In addition, neutrophil and platelet responses after Neumune treatment was similar in both the elderly and younger cohorts. Hollis-Eden plans to move the development of Neumune into further trials.
PharmAthene and Medarex issued positive results from a phase I trial of Valortim, an antibody against anthrax infection. This trial enrolled 46 healthy subjects who received either a single intravenous (IV) dose of Valortim ranging from 0.3 to 20.0 mg/kg or a single 100 mg intramuscular (IM) dose of Valortim. Treatment was well tolerated across all dose groups, with no serious adverse events reported. The most commonly reported adverse event was injection site reaction. Initial pharmacokinetic data revealed increasing peak concentrations and overall duration of exposure to antibody with increasing dose, and a half-life of approximately 26 days for IV administration, and approximately 32 days for IM dosing. In addition, the subjects who received Valortim at 1.0 mg/kg IV or 100 mg IM produced levels of antibodies that corresponded to protective levels in preclinical animal models. Based on the positive phase I data the companies plan to move Valortim into phase II trials.
October 16, 2006
Immatic's reported positive results from a phase I trial of IMA901, a renal cell cancer vaccine. This trial enrolled 28 subjects across six centers in Germany, the United Kingdom and Switzerland. Treatment was safe and well tolerated. Efficacy data revealed that 70% of the treated subjects displayed immune responses against tumor-associated antigens included in the IMA901 vaccine. This formation of immune responses against multiple targets correlated significantly with a stabilization of the disease and a decline in the tumor burden identified prior to commencement of the treatment (p<0.05). Based on these results Immatic's plans to initiate phase II trials by early 2007.
October 9, 2006
Baxter released positive preliminary results from a phase I/II trial of its vero-cell H5N1 vaccine for the treatment of influenza. This trial enrolled 270 subjects in Austria and Singapore, who were dosed with four different antigen concentrations ranging from 3.75mcg to 30mcg. Concentrations at 7.5mcg and 15mcg were tested with and without an adjuvant. The vaccine was well tolerated at all dose levels, with the most commonly reported adverse effects including injection site reaction, headache and fatigue. The vaccine was also found to be highly immunogenic, eliciting functional antibodies to H5N1 at the lowest dose level of 3.75mcg. Based on the results Baxter plans to initiate a phase III trial of the vaccine at the beginning of 2007.
September 25, 2006
SciClone issued positive results from a phase I trial of SCV-07 for the treatment of viral infections. This trial enrolled 24 subjects who were randomized to receive SCV-07 via an oral tablet, a subcutaneous injection, or a sublingual liquid dose, once a week for three weeks. Pharmacokinetic data indicated that SCV-07 had good oral bioavailability, with treatment safe. Similar circulating plasma concentrations to those obtained in previous phase 1 studies using a subcutaneous injection were also observed. Oral administration resulted in only a 10% plasma level variability between all subjects, demonstrating highly predictable plasma concentrations. SCV-07 administered sublingually did not result in bioavailability. SciClone plans to move development of the drug forward using different dosing regimes.
September 11, 2006
Genvec issued positive results from two phase I studies of HIV vaccine incorporating GenVec's adenovector-based technology. In the first study 40 subjects received the vaccine in a single dose of either 1e10 Particle Units (PU) or 1e11 PU. At both doses the vaccine was well tolerated and stimulation of T-cells against the multiple antigens contained in the vaccine occurred. In the second study 14 subjects were given a DNA prime followed by a boost with the HIV vaccine. Data revealed that the prime-boost combination produced more polyfunctional T-cells than either treatment alone. Based on these results Genvec plans to move development of the vaccine forward.
Nventa released positive results from a phase II trial of HspE7, a therapeutic vaccine, for the treatment of internal and external anal genital warts. This single-arm trial enrolled 30 HIV-negative men, all of who had internal warts and 10 of who had external warts. Subjects received three monthly injections of HspE7 at 1500 mcg and followed for 48 weeks. Treatment was well tolerated with headache being the most commonly reported adverse event (27%). Efficacy data revealed that at week 24, 11% of the subjects had complete response, defined as absence of warts and 67% had partial response. At 48 weeks 33% had complete response while 48% had partial response and a 71% mean decrease in volume of the genital warts was observed. Of the subjects with external genital warts, 70% had complete response. Based on these results, Nventa plans to move HspE7 into future trials.
September 5, 2006
Targeted Genetics released positive interim data from a phase I trial of tgAAC09, a potential HIV vaccine candidate based on recombinant adeno-associated virus vector serotype 2 (AAV2). This double-blind, placebo-controlled, dose-escalation study enrolled 50 subjects in Germany and Belgium and 30 subjects in India, all of who were healthy and HIV-negative. Each subject received a single intramuscular injection into the upper arm. A subset group also received a second dose of tgAAC09 to determine if repeat dosing is safe and boosts immune responses. The vaccine was determined to be safe and well tolerated at both dosing levels. Additionally, moderate immune responses were observed in the subset group who received the highest dose. A phase II trial of tgAAC09 is currently underway in South Africa, Uganda and Zambia.
ViroPharma and Wyeth reported positive preliminary data from a phase Ib trial of HCV-796, combined with pegylated interferon alfa-2b, for the treatment of hepatitis C. This randomized, double-blind, placebo-controlled, sequential-group study of ascending multiple doses enrolled 16 treatment naïve subjects with chronic hepatitis C infections. Subjects received HCV-796 or placebo (100 mg, 250 mg, 500 mg or 1000 mg) every 12 hours, for 14 days. On days 1 and 7 this was combined with peglyated interferon alfa-2b (1.5 ug/kg/dose). Safety data revealed no dose limiting toxicities. Efficacy data after 14 days of treatment determined that, across all dose groups, the combination of HCV-796 and pegylated interferon produced a mean viral reduction of between 3.3 and 3.5 log10 (99.95% to 99.97%) compared to 1.7 log10 with pegylated interferon alone. Based on these results, ViroPharma and Wyeth planned to initiate a phase II trial of HCV-796 at 500 mg to determine further dose response.
August 21, 2006
Advancis Pharmaceutical announced positive results from a phase III trial of Amoxicillin, for the treatment of pharyngitis/tonsillitis due to Group A streptococcal infections. This double- blind, double-dummy, randomized, parallel-group, 50-center non-inferiority trial enrolled 620 subjects who received a 775 mg Amoxicillin PULSYS tablet, once a day, for 10 days or 250 mg of penicillin, four times a day, for 10 days. The trial met the primary endpoint of statistical non- inferiority with 85% of the PULSYS group achieving bacterial eradication versus 83.4% of the penicillin group. Secondary endpoints met statistical non-inferiority as well in clinical cure rates at the test-of-cure visit and bacterial eradication rates at the late post-therapy visit. Based on these results, Advancis expected to file a NDA for once-daily Amoxicillin by late 2006 or early 2007.
Enzo Biochem issued positive long term results from a phase I trial, initiated in January of 2001, of HGTV43 for the treatment of HIV. This trial enrolled 5 subjects whose stem cells were collected, treated with HGTV43 ex vivo, than re-infused. Long-term safety data were positive with treatment well tolerated and no adverse events reported. Efficacy data collected demonstrated that the engineered stem cells were able to survive long term in vivo and to produce CD4+ cell progeny containing functioning antisense genes. At 12 months post-treatment antisense RNA was present in all five subjects. At 48 months, 4 subjects were available and 3 out of the 4 had antisense RNA present and at month 60 it was present in 1 out of the 3 subjects. In all the subjects tested, anti-HIV-1 antisense RNA was found in the CD34+ bone marrow cells. Enzo is further investigating HGTV43 in phase I/II trials at this time.
Tibotec Pharmaceuticals released positive results from a phase IIb trial of TMC125 for the treatment of HIV. This dose-finding, randomized, partially-blinded study enrolled 199 adult HIV-1 infected subjects who had received prior treatment. Subjects were randomized to receive 400 mg or 800 mg bid of TMC125 (n=159) with a background regimen or best available control regimen (n=40). Safety and tolerability data results demonstrated that the most commonly reported adverse events were diarrhea (22%), pyrexia (20%) and rash (20%) for the TMC125 treated group compared with 15%, 10% and 8%, respectively, for the active control group. Serious adverse events were reported by 27% of the TMC125 group and 18% of the control group. Efficacy data revealed that mean change from baseline in viral load at week 48 for the TMC125 400 mg and 800 mg bid and active control groups was -0.88, -1.01 and -0.14 log10 copies/ml, respectively. In the subjects with NNRTI resistance, those receiving TMC125 400mg or 800mg bid in combination with an optimized background regimen the viral load production was significantly greater than in the active control at 48 weeks, p=0.018 and p=0.002, respectively. Tibotec is conducting phase III trials of TMC125 at this time.
Transport Pharmaceuticals announced positive results from a phase IIb trial of device-enhanced acyclovir for the treatment of herpes labialis. This multi-center, randomized, double blind, placebo-controlled, clinic initiated, proof-of-concept trial enrolled 200 non-immunocompromised subjects, aged 18-75 years, with histories of recurrent cold sore outbreaks (3 or more annually). Safety and tolerability profiles were positive with reported adverse events similar to placebo. Efficacy data demonstrated that the median time to healing for the treatment group was 113 hours versus 148 hours for the placebo group (p= 0.02). The sub-group of participants who were treated at the first visible onset of infection displayed a time to healing of 71 hours versus 120 hours for the placebo group (p= 0.03). Transport plans to conduct additional phase II trials in the next year.
August 7, 2006
Acambis announced results from a phase II trial of MVA3000, an investigational smallpox vaccine for subjects with whom traditional vaccination is contraindicated. Safety data yielded a positive tolerability profile, with only mild adverse events reported. These events included injection site reactions, headache, fatigue, malaise and muscle ache. Efficacy data yielded positive results as well. Of the vaccine naïve subjects who received the highest dose of MVA3000, 75% seroconverted (a 4-fold or greater increase in vaccinia virus neutralizing antibodies) after two doses. Of the previously vaccinated subjects who received the highest dose of MVA3000, 88% seroconverted after two doses. This randomized, double-blind, placebo-controlled study enrolled 590 healthy subjects; 361 of whom had never received a smallpox vaccine (vaccine naïve) and 229 of whom had previously been vaccinated against smallpox. Based on these results, additional development of MVA3000 was planned.
Cerexa announced positive top-line results of a phase II trial of ceftaroline, for the treatment of complicated skin and skin structure infections (cSSSI). Efficacy data yielded a 96.8% clinical cure rate for the subjects treated with ceftaroline, versus an 88.9% cure rate for those treated with standard therapy. The microbiological response rate for the ceftaroline group was 95.2%, compared to 85.7% for the standard therapy group. Finally, ceftaroline demonstrated activity against gram-positive and gram-negative organisms isolated from patients in the study, including 100% of MRSA isolates inhibited at 0.5 mg/L or less. Safety data revealed a positive adverse event profile, with headache the most commonly reported event; control treatment yielded incidence of interstitial nephritis-related renal failure and "Red Man" syndrome. Subjects were treated with ceftaroline or standard therapy of vancomycin, with or without adjunctive aztreonam.
Cytrx announced positive preliminary results of a phase I trial of DP6-001, their investigational HIV DNA + protein vaccine. Preliminary trial data yielded a generally positive overall tolerability profile, and bioactivity measures indicated that the vaccine elicited both HIV-specific T-cell and antibody immune responses. Low grade adverse events included pain and redness at the injection site, mild body ache and low grade fever; there was some evidence that adverse events were dose proportional. This study enrolled 34 healthy volunteers, who received either a 3-dose low dose subcutaneous or intramuscular regimen of the drug, or a 3-dose high-dose intramuscular regimen of the drug. Additional results from the study were expected later in 2006.
June 5, 2006
PowderMed reported positive results of a phase I trial of their prophylactic DNA vaccine, for the treatment of influenza, in the journal Vaccine. Trial data yielded evidence of immunogenicity, with the highest trial dose eliciting seroprotective antibody responses. The level of this response for the highest dose was sufficient to meet EU CPMP immune response approvability criteria at 21 days, and all 3 doses met EU CPMP criteria at 56 days. This single ascending dose study enrolled 36 healthy volunteers, who received one of three doses of the vaccine (1 mcg, 2 mcg or 4 mcg).
Vical announced positive results of a phase I trial of their investigational West Nile Virus vaccine, at the American Society of Gene Therapy (ASGT) 2006 Annual Meeting in Baltimore. Results from the study demonstrated a positive safety profile, with no serious adverse events reported and a positive tolerability profile. Further, all subjects treated to date achieved neutralizing antibody WNV-specific responses following a 3-month vaccination schedule; a number of subjects achieved neutralizing antibody response following 2 doses. This open-label study had treated 11 healthy volunteers to date at the NIH Clinical Center; subjects received 4 mg of the vaccine once monthly for 3 months.
March 13, 2006
Pevion Biotech has announced positive results of a phase I trial of their investigational PEV3A malaria vaccine. This randomized, single blinded placebo-controlled study enrolled 46 healthy volunteers, who received three administrations of one of two or both synthetic peptide antigen components of the vaccine. Both peptide antigens were shown to be safe and well tolerated. Further, all subjects demonstrated positive seroconversion, indicating high immunogenicity, and elicited antibodies were shown to effectively inhibit malaria's ability to invade liver tissue in vitro. Significant immunogenicity was noted after the first two doses, indicating that a two-administration regimen might be sufficient for producing long-lasting immune response. Administration of both antigens together was not shown to cause competitive inhibition of immune response to either component. These results formed the basis for a recently initiated phase IIa trial, results of which were expected in mid 2006.
February 20, 2006
Acambis has reported positive results of a phase I trial of their investigational Clostridium difficile vaccine. Evidence of immunogenicity was observed, with significant increases in anti-toxin A and anti-toxin-B specific immunoglobulin G levels noted four weeks after the fist dose at the highest dose regimen, vs. placebo. Safety and tolerability results were also positive, with no serious adverse events reported and overall adverse events including those typically associated with intramuscular vaccine administration, including injection site tenderness, pain, redness, and headache). This randomized, double-blind, placebo-controlled study enrolled 50 healthy adult volunteers.
Schering-Plough reported positive results of a phase II trial of vicriviroc, for the treatment pf HIV infections. Primary efficacy data yielded a significant mean decrease in HIV RNA levels at 2 weeks, relative to placebo (25 mg: 0.93 log10; 50 mg: 1.18; 75 mg: 1.34; vs. 0.07 for placebo; p<0.001). A significantly greater portion of patients achieved virologic breakthrough (RNA > 50 copies/ml) with the three doses of the drug (56%, n=13/23; 41%, n=9/22; and 17% n=4/23, respectively), relative to placebo at 2 weeks (4%, n=1/24; p<0.001). This randomized, placebo controlled study enrolled 92 treatment naïve patients across 22 sites in Europe and Canada, who were randomized to receive one of three doses of the drug (25 mg, 50 mg or 85 mg) or placebo once daily for 14 days, followed by a combination regimen of either vicriviroc or efavirenz, in addition to Combivir.
February 13, 2006
Nabi Biopharmaceuticals has reported positive results of a phase I trial of their S. aureus Type 336 vaccine, for the prevention of Staphylococcus aureus infections. The vaccine was seen to be safe and well tolerated, and dose-related increases in anti-S. aureus Type 336 antibodies were noted. This double-blind, placebo-controlled study enrolled 48 healthy volunteers, who were randomized to receive 1 of 4 doses of the vaccine or placebo (9 vaccine:3 placebo per dose group). Based on these results, the company announced plans to initiate a phase II proof of concept study in the near future.
February 6, 2006
DOR BioPharma has announced positive results of a phase I trial of their investigational ricin toxin vaccine RiVax. Primary safety data indicated that the drug was well tolerated, with only mild, transient reactions noted. Preliminary immunogenicity was noted, with serum anti-ricin-toxin antibodies detected up to 127 days after the last administration of the drug, without the use of a vaccine adjuvant. This open-label dose-escalation study enrolled 15 subjects at the University of Texas Southwestern Medical Center. Subjects received 1 of 3 doses of the drug via once-monthly injection for 3 months.
May 9, 2005
Acambis and Baxter Healthcare have issued results of a phase I trial of its investigational attenuated smallpox vaccine MVA3000. Results from the study demonstrated a positive overall safety profile, with no occurrence of unexpected or serious adverse events. Secondary evaluation of immune response was also positive, with 97% of subjects seroconverting to vaccinia virus-specific antibodies and 82% seroconverting to vaccinia neutralizing antibodies after 2 doses. This double-blind, placebo-controlled study enrolled a total of 110 healthy volunteers who had not previously received smallpox vaccination, who were randomized 4:1 to receive the vaccine or placebo. Based on these results, the companies announced plans to initiate a phase II trial of the drug in coming weeks, and additional phase I trials later in 2005.
March 28, 2005
ID Biomedical announced positive results of several phase I studies of their Pneumococcal Group-Common Vaccine (PGCvax), under development for the prevention of diseases caused by Streptococcus pneumoniae. Combined results indicated that the drug was safe and well tolerated across multiple age groups, including pediatric patients and the elderly. In addition, significant antibody responses were noted in 92% of young adults and 85% of elderly subjects receiving optimal doses of the vaccine, with 9.0 fold mean increase for both groups (p<0.0001). These safety and immunogenicity trials enrolled toddlers, young adults and elderly subjects, who received one or 2 doses of either the drug or placebo. Based on these results, the company announced that it had received clearance from Canadian regulatory authorities to initiate a Phase 1 study of the drug in 75 infants.
March 14, 2005
The Immune Response Corporation has issued positive results of a pair of phase II trials of their investigational HIV vaccine Remune (RG-83894). Results from the first study (the “REMIT” study), an follow-up to a double-blind phase II trial conducted in Spain (the “STIR-2102” trial), indicated that subjects who had received the drug in both STIR-2102 and REMIT were less likely to experience an efficacy failure endpoint at 48 weeks, versus subjects receiving control therapy with Incomplete Freud’s Adjuvant (IFA) in one or both trials. A correlation was noted between both the number of doses of Remune and the magnitude HIV-specific immune response, and the length of delay of virologic failure after treatment conclusion. The second study found that Remune successfully maintained CD4+ T-cell counts through 28 weeks, while these levels declined in subjects receiving either IFA or placebo. The REMIT study enrolled 39 patients who had participated previously in the double-blind STIR-2102 trial; these subjects, who had received either Remune or IFA in STIR-2102, were re-randomized to receive one of the treatments again for 48 weeks, yielding a total of 4 treatment cohorts (Remune-Remune, n=9; Remune-IFA, n=10; IFA-Remune, n=12; or IFA-IFA, n=8). The second trial, a multi-center, single-blind, randomized study, enrolled 51 patients who received three doses of Remune (n=19), IFA (n=11) or saline (n=10) at weeks 0, 12 and 24, or a single-dose of Remune at week 0 (n=10); the disease status of all subjects , as indicated by CD4+ T-cell counts, was followed through 28 weeks. The company announced that the results of these trials would serve to support the design of registration trials in the near future.
February 28, 2005
Targeted Genetics, in collaboration with the International AIDS Vaccine Initiative, has issued preliminary data from a phase I trial of their investigational recombinant adeno-associated viral vector based HIV/AIDS vaccine candidate tgAAC09. Results from the ongoing study indicated that the drug met its primary safety endpoint, with no serious adverse events noted and a favorable tolerability profile. Trial doses of the vaccine did not elicit significant immune response. This double-blind, placebo-controlled, dose-escalation safety study enrolled 50 healthy, HIV-negative subjects across sites in Belgium and Germany. Subjects received a single intramuscular injection of the drug or placebo. The company announced that they were expanding the study, enrolling 30 additional healthy subjects in India, and administering a second round of treatment to a subset of patients in an effort to increase immune response, based on these initial results.
January 18, 2005
Nabi Biopharmaceuticals issued positive results of a phase I/II trial of Altastaph (S. aureus human immune globulin), for the treatment of persistent bacteremia. Trial data demonstrated preliminary evidence of efficacy, with a 36% reduction in time from administration to hospital discharge, vs. placebo (9 vs. 14 days, respectively). Furthermore, the drug was found to be safe and well tolerated, with no serious treatment-related adverse events observed. The double-blinded, placebo-controlled, randomized trial enrolled 40 patients with persistent S. aureus blood stream infections (bacteremia), who received either daily Altastaph or placebo in addition to standard-of-care treatment including antibiotics. Based pm these results, the company announced plans to meet with US and European regulatory authorities to discuss the next steps in the development of Altastaph.
Vaxin Inc. has issued positive results of a phase I study of the company’s proprietary nasal influenza vaccine. Data from the trial yielded a positive pharmacokinetic profile, with a single dose of the nasal vaccine producing a 4-fold increase in serum influenza antibody levels in 67% of subjects; a second dose raised this portion to 83%. This 4-fold increase corresponded to literature-established “protective” levels, and was observed despite the fact that the nasal vaccine carried a total dose roughly 1000 times lower than a subcutaneous formulation of the vaccine. The study randomized a total of 24 participants to receive one of 3 subcutaneous or 1 intranasal regimens of the drug. Based on these results, the company announced plans for an expanded phase I program, with an additional monovalent phase I trial to be initiated before the end of 2005.
November 22, 2004
Boehringer-Ingelheim has reported positive results of a phase III trial of tipranavir, their investigational protease inhibitor for the treatment of HIV infections. Results from a 24-week interim analysis have indicate that the drug is efficacious in reducing viral load, with a significantly greater portion of subjects receiving tipranavir plus low-dose ritonavir (T/r) achieving treatment response (a 1 log(10) or greater decrease) than in those receiving a comparator protease inhibitor plus low-dose ritonavir (CPI/r) (41.0% vs. 14.9%; p<0.001). Furthermore, subjects receiving T/r experienced a significantly greater portion of subjects achieving preset total viral load levels of 400 copies/ml and 50 copies/ml (p<0.0001), and significant greater increases in CD4+ count (p=0.02), than in subjects taking CPI/r. The randomized, approved-therapy controlled, open-label trial was designed to study the safety and efficacy of T/r versus CPI/r, in 863 treatment-experienced patients with documented protease-inhibitor resistance. This trial, along with a second phase III study, formed the basis of the company’s NDA application, submitted on October 22, 2004.<
MacroChem has announced positive results of a phase I trial of EcoNail (SEPA plus econazole), an investigational antifungal lacquer for the treatment of onychomycosis, a common fungal infection of the nail. Trial data indicate that the study met its primary safety and pharmacokinetic endpoints, with no serious drug-related adverse events and no detectable systemic absorption. The randomized, double-blind, placebo controlled trial enrolled 18 patients suffering from onychomycosis across 2 clinical sites in the US. Subjects received twice daily applications of either EcoNail or placebo lacquer 6 weeks, and were monitored for adverse events and systemic absorption. An ongoing open-label extension is currently underway, with all patients receiving EcoNail once daily to all nails for an additional 12 weeks, and MacroChem announced plans to initiate a preliminary efficacy trial in early 2005.
PowderMed has issued results of their first phase I trial of their DNA influenza vaccine candidate. Results indicate that the trial met its primary endpoints, with all trial doses of the drug being well tolerated and a significant number of subjects exhibiting immune response sufficient to meet standards established for European approval after 56 days. Furthermore, the highest dose of the drug met the criteria after just 21 days, and 100% of subjects receiving this dose achieved seroprotective antibody levels. This open-label trial enrolled 36 healthy adult volunteers, who were randomized to receive one of three single doses of the vaccine (1, 2 and 4 micrograms), followed by a 56 day follow-up observation.
The Immune Response Corporation presented data from their ongoing phase II study of Remune, their investigational antiretroviral vaccine for the treatment of HIV, at the 7th International Congress on Drug Therapy in HIV Infection in Glasgow, Scotland. Preliminary results from the 37 subjects having thus far received treatment demonstrate positive trends in several immune-response indicators, including stabilization of total CD4+ T-cell counts, increased HIV-specific CD8+ memory T-cells, and decreased levels of activated CD38+ T-cells, following treatment. This multi-center, single-blind study has to date randomized 37 of a projected 51 treatment naïve HIV-positive subjects to receive one of two treatment regimens of Remune (one injection Remune & two placebo or three injections Remune), or Incomplete Freund's Adjuvant (a non-targeted immunostimulatory) or placebo over 28 weeks; the four arms of the study each received injections at trial initiation and weeks 12 and 24. Immune Response, following these results, has announced plans for a rollover study which will include treatment with both Remune and IR103, another of the company’s investigational antiretroviral drugs.
November 8, 2004
Anadys Pharmaceuticals has reported positive results of a phase I b trial of isatoribine, a Toll-like receptor 7 agonist for the treatment of chronic hepatitis C (HCV) infections. Trial data indicated that the drug was biologically active, with significant changes in interferon-alpha-mediated disease markers, and produced a significant 82% reduction in serum viral load after seven days at the highest dosing regimen. Treatment was also observed to be safe and well tolerated, with no discontinuations or regimen changes due to adverse events. This dose escalating, open-label study enrolled a total of 32 adult HCV patients across 2 European centers into one of four seven-day dosing regimens (200 mg, 400 mg, 600 mg or 800 mg daily). Anadys announced that the trial would serve as the basis for upcoming trials of their investigational isatoribine pro-drug ANA975.
Inhibitex reported positive results of a phase I trial of their investigational anti-microbial monoclonal antibody Aurexis, for the adjuvant treatment of serious Staphylococcus aureus (S. aureus) infections, at the 44th annual Interscience Conference on Antimicrobial Agents and Chemotherapy. Trial results showed Aurexis was generally safe and well-tolerated by the study participants, and had an elimination half life of Aurexis was approximately 21 days. This open-label, dose-escalating trial enrolled 19 healthy patients who receive one of four dose levels of Aurexis. The company announced that they expected to use these findings to support ongoing enrollment efforts in their phase II trial of the drug plus standard antibiotic therapy in patients with hematological S. aureus infections.
Microscience issued positive results of a phase I trial of their oral hepatitis B (HBV) vaccine spi-VECTM. Study data met their primary safety endpoint, with no significant adverse events noted. Further, the drug was shown to be significantly immunogenic, with all subjects generating a T-cell response to hepatitis B core antigen (HBcAg), and 95% subjects in the high-dose group exhibited an immune response marked by the gamma interferon secretion and IL-5 down-regulation in stimulated T-cells. This type of immune response is known to promote viral clearance in chronic HBV infections. This open-label dose-escalating study enrolled 30 healthy volunteers, who received two single escalating oral doses of the vaccine 56 days apart. Microscience announced that they were planning phase II trials for spi-VECTM, based upon these results.
Theravance has reported results from a phase II study of their investigational antibiotic telavancin (TD-6424), for the treatment of Gram-positive skin and skin structure infections (cSSSI). Results indicated that the drug demonstrated comparable efficacy and improved dosing options than standard therapy. Specifically, the drug produced statistically non-distinct cure rates in patients with cSSSIs, including an 82% cure rate among the subset of patients with cSSSIs caused by methycillin-resistant S. aureus infections (vs. 69% for standard therapy with vancomycin), and the minimum inhibitory concentration were lower for telavancin than vancomycin for all S. aureus strains. This exploratory standard-therapy-controlled safety and efficacy trial enrolled a total of 167 subjects with cSSSIs. These data will be used to support ongoing phase III studies of the drug.<
October 18, 2004
Immtech International has reported positive results of a phase I dose-escalation trial of DB289, for the treatment of malaria. Study data met their primary pharmacokinetic endpoint, with all dosing regimens tested reaching plasma levels considered to be within the therapeutic range for the treatment of malaria. This open-label, multi-ethnic study randomized 75 healthy volunteers to receive one of three doses of the drug (200 mg, 400 mg or 600 mg) either once or twice daily for three days. Dosing information from these results has been incorporated into Immtech’s upcoming phase II standard-care-combination study in Thailand.
August 16, 2004
ID Biomedical reported preliminary results from an expanded phase II trial investigating StreptAvax, their streptococcal vaccine. No subject in the clinical trial has developed antibodies that cross-reacted with human tissues, one of the primary safety endpoints. There have been no vaccine-related serious adverse events. Results showed that the vaccine induced high titers of antibodies to all targeted (26) serotypes of group A streptococcus. All subjects have completed at least 194 days of observation since vaccine exposure. ID Biomedical plans to begin their next phase of trials in Q1 2005.
Oscient Pharmaceuticals reported positive results from a phase II trial investigating Ramoplanin, a glycolipodepsipeptide antibiotics for the treatment of Clostridium difficile-associated diarrhea (CDAD). The study compared Ramoplanin (200 mg) twice daily, Ramoplanin (400 mg) twice daily and vancomycin (125 mg) four times daily. The primary endpoint of the trial, response rates at 7-14 days post therapy, showed a 71% response rate with Ramoplanin (400mg) compared to 78% with vancomycin. Results showed that non-inferiority was observed, but not statistically demonstrated because the response rates of all arms were lower than the previously published vancomycin response rates. Ramoplanin (400 mg) and vancomycin had response rates at end of therapy of 85.2% and 85.7%, respectively. The open-label, non-inferiority study enrolled 87 subjects with CDAD at 24 sites in the U.S. Adverse events profiles were similar for both drugs. Oscient hopes to move forward with phase III trials by the end of 2004.
July 5, 2004
Dynavax Technologies and UCB Pharma have reported positive results of their phase I pediatric trial of AIC, their investigational ragweed allergy vaccine. Results have indicated that the drug is well tolerated in children and adolescents. The dose-escalating, open-label study enrolled 24 children between the ages of 9 and 17, all of whom had documented ragweed allergy; subjects were divided into three dosing cohorts, which each received increasing doses of AIC. Overall safety and tolerability were excellent, with only minor, localized, injection-site reactions reported and no serious adverse incidents. Based on these data, the companies announced plans to extend their clinical investigations into the use of AIC as a prophylactic against ragweed-allergy-induced sequelae, including asthma and chronic sinusitis.
May 10, 2004
Protein Sciences Corporation reported positive results from a phase II b trial investigating FluBlOk, a vaccine for the prevention of influenza. Results showed that FluBlOk was safe and statistically more immunogenic against the H3 influenza strain when administered at higher doses compared with the current licensed vaccine. Data demonstrated that at least 20% more subjects receiving high doses of FluBlOk achieved antibody levels that are associated with better protection against an H3 influenza virus than subjects receiving the licensed vaccine. FluBlOk had a slightly lower rate of minor side effects than the licensed vaccine. The double-blinded study enrolled 399 elderly subjects at three sites in the U.S.
March 22, 2004
Pharmexa reported positive results from a phase I trial investigating HER-2 Protein AutoVac, a vaccine for the treatment of breast cancer. Data showed that the vaccine was well tolerated and that induced significant HER-2 specific antibodies in breast cancer patients. Results showed that six subjects demonstrated HER-2 specific antibody responses. Subjects received four injections of the vaccine formulated in a standard aluminium adjuvant. The study enrolled ten subjects and was conducted at the Ireland Cancer Center in Cleveland, Ohio and the Magee Women's Hospital in Pittsburgh, Pennsylvania. Full results will be reported at the 4th European Breast Cancer Conference (EBCC) in Hamburg, Germany. Pharmexa expects to commence phase II trials in the second half of 2004.
Transgene reported results from a phase II trial investigating MVA-HPV-IL2, a vaccine for human papilloma virus (HPV)-related diseases. Data showed that partial clinical and histological responses were observed in five subjects treated with a high dose. The study enrolled 28 subjects with High-Grade Cervical Intraepithelial Neoplasia CIN 2/3 in France. No indication of CIN regression was observed in the 12 subjects treated with the low dose. Subjects were given different doses (5.105 pfu and 5.107 pfu) administered sub-cutaneously. Subjects were treated with MVA-HPV-IL2 on days 1, 8 and 15, with conisation performed at week six. The primary endpoint was, demonstrated clinical and histological efficacy measured by the elimination of the CIN lesions at six weeks. MVA-HPV-IL2 was simultaneously tested in 20 subjects with vulvar intra-epithelial neoplasia (VIN3).
March 8, 2004
Basilea Pharmaceutica AG reported positive results from a phase II trial investigating BAL5788, a cephalosporin antibiotic for the treatment of complicated skin and skin structure infections (cSSSI). Results showed that all subjects were cured with improvement typically observed within the first days of treatment. In addition, the safety of BAL5788 was similar to other cephalosporins, with mild to moderate nausea/vomiting being the most frequent side effect observed. The study enrolled 35 subjects and investigated the safety and efficacy of BAL5788 in hospitalized subjects with deep muscle and/or fascia infections caused by streptococci and staphylococci, including methicillin-resistant Staphylococcus aureus (MRSA). Based on these results, the company plans to initiate a phase III trial program.
VaxGen reported results from a phase I trial investigating rPA102, a recombinant Protective Antigen vaccine for the prevention of anthrax infection. Results demonstrated that the immune responses to rPA102 at the higher doses (50 ug and 75 ug) were comparable to that of Anthrax Vaccine Adsorbed (AVA), the present standard vaccine. In addition, rPA102 showed this response with less aluminum adjuvant, an immune stimulant, then in AVA. The double-blind, multi-center study was designed to examine the safety and immune response of a range of doses of rPA102 compared to AVA. Subjects received doses of rPA102 escalated from 5 ug through 75 ug, and all doses were formulated with a standard amount of adjuvant (82.5 ug aluminum hydroxide). Results were reported at the International Conference on Emerging Infectious Diseases (ICEID) in Atlanta, Georgia. The study was funded by the National Institute of Allergy and Infectious Diseases (NIAID). VaxGen plans to initiate two phase II trials of rPA102 this year.
November 17, 2003
VaxGen reported negative results from a phase III trial investigating AIDSVAX B/E (rgp 120), a vaccine for the prevention of HIV infection. Results showed the vaccine did not show efficacy for either primary or secondary endpoints. Results showed that 105 subjects who received placebo became infected with HIV compared with 106 subjects who received AIDSVAX B/E. The vaccine appeared to be well tolerated with no serious adverse events reported. The randomized, double-blind, placebo-controlled study enrolled 2,546 intravenous drug users at 17 sites in Bangkok, Thailand. The trial was designed to evaluate the vaccine against the blood-borne transmission of HIV subtype E and one strain of HIV subtype B. Subjects were given a total of seven injections, administered at months 0, 1, 6, 12, 18, 24 and 30.
September 2, 2003
Immtech reported positive results from the first stage in a phase IIa trial investigating DB289 for the treatment of malaria. Results showed that on average the malaria parasite was eliminated from the blood in approximately 95% of the subjects in less than 3 days. Subjects tested remained completely parasite free 28 days after treatment. In addition, data also indicated that the fever associated with malaria was on average eliminated within 16 hours for the same group of subjects. Data demonstrated that DB289 was safe to administer and was efficacious in the subjects tested. Treatment was well tolerated and no adverse effects were reported with DB289. The trial is being conducted at a hospital clinic in Thailand.
May 12, 2003
ID Biomedical reported positive results from a phase II trial investigating StreptAvax, a vaccine for the prevention of streptococci infection. Results showed that the immunogenicity of the vaccine was highly significant. Data demonstrated that the subunit vaccine generated antibody responses that were similar to earlier results in both magnitude and breadth. In addition, results showed that the median rate of seropositivity after immunization matched 25 of the 26 M serotypes contained in the vaccine. The randomized, blinded, and comparator-controlled study is providing data on the performance of StreptAvax given on a schedule identical to that used for a hepatitis A vaccine which will be used as comparator in future pediatric studies.
April 21, 2003
DynPort Vaccine Company reported positive results from a phase I trial investigating their cell-cultured smallpox vaccine (CCSV). Results showed that 100% of the 350 subjects exhibited a positive response to either the CCSV or the original Dryvax smallpox vaccine. The incidence of vaccine-related fatigue, application site rash, increased temperature, headache, lymphangitis and nausea was at least 8% less common for subjects receiving CCSV compared with Dryvax. The double-blind study randomized 350 healthy subjects into five separate cohorts. The first four cohorts received undiluted CCSV or Dryvax, the fifth cohort provided preliminary information on the safety and efficacy of CCSV dilutions of up to one part per 50. In that fifth cohort, 71% of subjects developed a positive response to the CCSV vaccination.
March 4, 2003
Microscience reported positive results from a phase I trial investigating Micro-TY, their oral typhoid vaccine. Results show the vaccine was safe, well tolerated, and highly immunogenic. Subjects who received the highest dose levels of treatment experienced an excellent immune response, measured by mucosal and systemic responses. The incidence of adverse events was similar to those found in the placebo group. No bacteraemias attributable to the treatment was found. The randomized, double blind, multi-center, placebo-controlled, study enrolled 60 healthy adult subjects. The live attenuated vaccine was administered in a new oral, low dose, freeze-dried formulation.
VaxGen reported negative results from a phase III trial investigating AIDSVAX (rgp120) for the prevention of HIV infection. Results showed the vaccine did not demonstrate a significantly significant reduction of HIV infection within the study group as a whole. The reduction of infection among all subjects treated with the vaccine was 3.8% compared to placebo. Data pertaining to certain racial subgroups seem to indicate a positive efficacy trend. There were 67% fewer HIV infections among ethnic minorities and 78% fewer HIV infections among black subjects compared to placebo. Further data analysis is needed to confirm these results. The randomized, double blind, placebo-controlled study enrolled 5,417 subjects deemed at higher risk for HIV infection. Subjects were administered seven vaccinations via injection during the 36-month trial. The trial was conducted in the U.S., Canada, Puerto Rico, and the Netherlands. VaxGen is continuing testing on the vaccine for other HIV subtypes and in alternative formulations.
February 24, 2003
ID Biomedical reported positive preliminary results from a challenge study with FluINsure, an intranasal influenza vaccine. Data showed the trial reached both the saftey and clinical efficacy endpoints. Results showed that 86% of subjects who received two doses of vaccine achieved no illness criteria compared to 52% of subjects who received placebo. The vaccine resulted in complete elimination of all measure of systemic illness such as fever, headache, or myalgia/arthralgia in the two-dose group. The one-dose group did not attain significant differences from placebo with respect to the no illness criteria, but did show a 40% reduction in systemic illness. The randomized, blinded, placebo controlled study enrolled 75 healthy subjects. All subjects were challenged with influenza and given either one or two doses of FluINsure or placebo.
January 6, 2003
Acambis reported positive preliminary results from a phase I trial investigating ChimeriVax-Dengue for the prevention of Dengue fever. Preliminary data showed that the vaccine was well tolerated with no serious adverse reactions reported. Analysis showed that 100% of the subjects developed neutralizing antibodies to the homologous Dengue 2 serotype virus within one month of vaccination, and 96% of the subjects developed antibodies to the wild-type Dengue 2 virus. The seroconversion rate was similar at both dose levels tested and prior immunity to yellow fever did not inhibit response to the vaccine. The randomized, double blind trial enrolled 42 subjects who had not previously been exposed to yellow fever.
December 16, 2002
Cytos reported positive initial results from a phase I trial investigating their Immunodrug Q-Derp1, a model antigen for the prevention of various major chronic diseases. The open randomized study enrolled 24 healthy subjects and was designed to evaluate the safety, tolerability and immunogenicity of the Q carrier. All 24 subjects immunized with one initial Q-Derp1 injection reported no systemic side effects and only three subjects reported mild irritation at the injection site. Two booster shots will follow after 4 and 12 weeks. To assess the immunogenicity of Q-Derp1, the production of specific antibodies as well as induced T cell responses will be monitored over a period of one year.
November 4, 2002
PRIMABioMed reported positive preliminary results of a phase I trial investigating their dendritic cell based therapy as a cancer treatment. The therapy recognizes a cancer protein that is highly expressed in breast, ovarian, lung and prostate cancers and so is able to stimulate a specific immune response. The study consisted of 10 subjects with various cancers, treated with three doses of therapy, over a 12-week period. Data demonstrated the therapy was safe and was able to produce the specific immunological response. The study was conducted at the Austin Research Institute (ARI) and the Austin & Repatriation Medical Centre in Melbourne, Australia.
October 21, 2002
Antigenics reported positive results from a phase II study of their cancer vaccine, Oncophage. The treatment uses surgically removed tumor cells to develop a personalized vaccine in order to reprogram the body's immune system to target and destroy only cancer cells. The phase II study, involving 39 subjects with stage IV melanoma, suggested a correlation between Oncophage-induced immunological activity and a measurable clinical response. Of the 28 subjects who had residual disease after surgery, two experienced complete disappearance of disease after treatment with Oncophage. Of the 23 subjects tested for immunological response, significant increases in melanoma-specific T-cell activity were observed in 11 subjects, five of whom also experienced complete response or long-term disease stabilization.
October 14, 2002
AuRx reported positive results for a phase I/II trial for the treatment of genital herpes. The HSV-2 theracine vaccine produced no adverse events and the side effects were similar to that of the placebo. The vaccine reduced the number of genital herpes cases three fold versus the previous year. In 37.5% of subjects the recurrent episodes of HSV-2 were completely prevented. Of subjects vaccinated, 50% had fewer recurrences and 45% had fewer illness days than the placebo.
Positive phase I clinical trial results were reported for FluINsure, a nonliving flu vaccine from ID Biomedical. The study, a randomized double-blinded and placebo-controlled trial, was found to be well tolerated by healthy adults. The vaccine showed significant increases in both serum hemagglutination inhibiting (HAI) antibody and in virus-specific secretory IgA antibodies in the nose. Increases were shown for all three types of influenza viruses (A/H1N1, A/H3N2, and B) represented in the vaccine. Subjects who were administered active vaccine had an average increase in serum HAI antibody levels of 3.2-fold of normal protection levels. In a high majority of subjects, without existing immunity to the A/H1N1, A/H3N2, or B viruses, a significant serum and/or nasal antibody response was reported.
August 19, 2002
While the primary endpoint was not met in a phase III trial of Provenge, an investigational vaccine for the treatment of late-stage prostate cancer, preliminary analyses showed some favorable results. The randomized, placebo-controlled study, which involved 127 subjects with late-stage, metastatic, hormone-resistant prostate cancer, evaluated the time to objective disease progression as its primary endpoint. The clinical benefit in the 82 subjects treated with Provenge approached, but did not achieve, the pre-specified primary endpoint when compared to placebo. Investigators were encouraged, however, by the fact that there was a statistically significant correlation between the subjects' Gleason scores and their therapeutic response to Provenge. Subjects with Gleason scores less than or equal to 7 had a median time to disease progression of 16 weeks, compared to nine weeks for the placebo group. Since approximately 75% of hormone resistant patients have Gleason scores of 7 or less, these results are promising. Provenge is being developed by Dendreon.
August 12, 2002
Large Scale Biology Corporation announced favorable safety results of a phase I trial of its personalized therapeutic vaccines for the treatment of non-Hodgkin's lymphoma (NHL). The plant-expressed single-chain NHL vaccines, which were manufactured individually from each subject's specific tumor RNA sequences, were administered six times over a period of six months. 16 subjects received either a low-dose or a high-dose of their personalized vaccine, with or without Granulocyte Macrophage Colony Stimulating Factor (GM-CSF) as an adjuvant therapy. Results showed that the personalized vaccines were well tolerated in all subjects, and no serious adverse events were reported.
July 8, 2002
Positive follow-up data was obtained from a phase I/II trial of Cell Genesys' Gvax lung cancer vaccine. The multicenter trial, which evaluated vaccine made directly from subject tumor biopsies, included non-small cell lung cancer (NSCLC) subjects with either advanced heavily pretreated disease or early stage disease with high risk of relapse after surgery. Data for 33 advanced disease subjects showed a median survival of 8.0 months, compared to the reported 5.7-7.0 months for docetaxel, the approved second-line chemotherapy for such patients, or 4.6 months for best supportive care. Two of the three subjects with advanced disease who achieved a durable complete response had a lung cancer subtype referred to as bronchoalveolar carcinoma (BAC); this diagnosis was found to be the only identifiable predictor of increased survival in the advanced subject group. Based on the study data, the company plans to focus the next trials of the vaccine on BAC, as opposed to initiating a trial for all NSCLC types.
July 1, 2002
BioCryst Pharmaceuticals has decided to discontinue development of peramivir based on preliminary data from a phase III trial. The placebo-controlled trial was designed to evaluate peramivir in the treatment of acute influenza A and influenza B infections in otherwise healthy adults. A total of 1,246 subjects were randomized to one of three treatment groups over four flu seasons; 694 subjects were evaluable based on the presence of laboratory-confirmed influenza virus infection. No statistically significant difference was observed between peramivir- and placebo-treated groups in the primary efficacy endpoint - length of time from the first dose to the onset of clinically significant relief of influenza symptoms.
June 10, 2002
Phase II trial results suggest that Theratechnologies' ThGRF has a positive effect on cell-mediated immune response. The double-blind, multicenter trial evaluated the efficacy of ThGRF on the immune response to influenza vaccination. The trial included 87 subjects with an average age of 74.6 years. Subjects were randomized to receive daily treatment with 1.0 mg ThGRF, 2.0 mg ThGRF or placebo for four weeks before and four weeks after influenza vaccination. During the study period, the antigen-driven T lymphocyte proliferation response was statistically increased at the 2.0 mg dose (compared to placebo) for each of the three strains used in the vaccine. The response was also sustained following cessation of ThGRF treatment: the proliferation response was statistically higher in the 2.0 mg group when compared to the placebo group in the 8-20 week period.
April 15, 2002
Preliminary phase I/IIa trial results indicate that three dosage levels of a therapeutic vaccine utilizing Mojave Therapeutics' Javelin antigen delivery system are safe and well tolerated. The trial included 27 subjects with stage III or stage IV melanoma. Subjects each received five subcutaneous injections comprised of a recombinant human heat shock protein (HSP-70) complexed with one, 10 or 100 micrograms each of tyrosinase and gp100 peptides modified with the Javelin sequence. Of 15 subjects evaluated for immune responses, nine exhibited a positive immune response. At this time, none of the nine responders have shown evidence of disease progression.
January 7, 2002
Positive results from a phase I/II trial indicate that immunization with hepatitis B surface antigen, (HbsAg) co-administered with Dynavax's proprietary immunostimulatory DNA sequences (ISS), produced protective antibody levels in 31 of 32 subjects over all dose levels. During the two-month double-blind study, 48 subjects received two immunizations. After a single immunization at the highest dose tested, the vaccine produced protective antibodies in 88% of treatment subjects. Currently available vaccines for the treatment of hepatitis B require three vaccinations over a six-month period to achieve the response seen with this vaccine regimen. This combination vaccine is being jointly developed by Dynavax Technologies and Triangle Pharmaceuticals.