September 11, 2017
Symbiomix Therapeutics issued results of a phase III, randomized, double-blind, dose-ranging, placebo-controlled, multicenter study of Solosec for the treatment of bacterial vaginosis (BV). In the SYM-1219-301 study, women with BV were randomized to 2g secnidazole or placebo, each administered as a single oral dose. The 2g dose of secnidazole proved superior to placebo on all primary and secondary outcomes and was well-tolerated. In the modified intent-to-treat (mITT) population of 189 women, clinical outcome responder rates were 53.3% for 2g secnidazole compared with 19.3% for placebo (p<0.001). The clinical outcome responder rate analysis was 58.9% for 2g secnidazole compared with 24.6% for placebo (p<0.001) when women with abnormal discharge that is inconsistent with BV were included as clinical outcome responders. Clinical cure rates based on the 2016 FDA guidance of seven to 14 days after treatment were 64.0% for 2g secnidazole compared with 26.4% for placebo. Based on the investigator’s clinical assessment at the test of cure, significantly more patients receiving single-dose secnidazole 2g compared to placebo required no additional BV treatment (68.0% vs 29.6%; p<0.001). The overall adverse event rate was 34.4% for single-dose secnidazole 2g compared to 21.9% for placebo. Most adverse events were mild or moderate in intensity and non-serious. The FDA accepted the NDA for Solosec oral granules in March 2017. In accordance with the FDA’s priority six-month review designation, the agency has established a user-fee goal date under the Prescription Drug User Fee Act (PDUFA) of September 2017.
July 24, 2017
Paratek Pharmaceuticals announced positive top-line results from a pivotal phase III clinical study comparing omadacycline to twice-daily oral linezolid in the treatment of acute bacterial skin and skin structure infections (ABSSSI). The OASIS-2 study was a randomized, double-blind, multicenter study that enrolled 735 adult subjects with moderate to severe ABSSSI at 33 centers in the U.S. The early clinical response (ECR), 48 to 72 hours after the first dose of study drug, for omadacycline was 87.5% compared to 82.5% for linezolid. Omadacycline met statistical non-inferiority compared to linezolid for the EMA-specified co-primary endpoints at the post therapy evaluation, seven to 14 days after completion of therapy in the modified intent-to-treat (mITT) population and the Clinically Evaluable (CE) populations. Clinical success rates at post therapy evaluation in the mITT population for the omadacycline and linezolid arms were 84.2% vs. 80.8%, respectively; and in the CE population were 97.9% vs. 95.5%, respectively. The study met all of its primary and secondary endpoints required to support approval for this indication by the FDA and the EMA.
April 17, 2017
Zavante Therapeutics issued results of a phase II/III trial of ZOLYD (fosfomycin for injection, also known as ZTI-01 for complicated urinary tract infections (cUTI), including acute pyelonephritis (AP). The ZEUS study was a multicenter, randomized, double-blind trial designed to evaluate the safety and efficacy of ZOLYD. The primary endpoint of overall success, defined as clinical cure plus microbiologic eradication, was assessed in the microbiologic-modified intent-to-treat population at the test-of-cure visit (day 19). In the study, ZOLYD met the primary endpoint of statistical non-inferiority compared to piperacillin/tazobactam, with an overall success rate of 64.7% (119/184 patients) versus 54.5% (97/178 patients), respectively, a treatment difference of 10.2% (95% CI: -0.4, 20.8). Clinical cure rates were high and similar between treatment groups (90.8% vs. 91.6%, respectively). Zavante expects to submit a new drug application to the FDA in early 2018.
April 10, 2017
XBiotech issued results of a double-blind, placebo-controlled, phase I-II study evaluating the safety and efficacy of 514G3 for the treatment of Staphylococcus aureus bloodstream infections. In the study, hospitalized adult patients with confirmed blood infections were randomized 3:1 (514G3 vs placebo) during a dose escalation phase to establish a phase II dose. The phase II portion was randomized 2:1 at the established phase II dose of 40mg/kg. A total of 52 patients were enrolled; 36 received 514G3 and 16 received placebo. Thirty of the 36 patients that were given 514G3 received the established phase II dose (40mg/kg). No drug-related adverse events were observed at any of the dose escalation levels and the 40mg/kg phase II dose was established without any dose-limiting toxicities (DLTs). A total of 28 SAEs in 15 patients were reported during the study period, including four deaths. There was a 49% relative risk reduction for the overall incidence of SAEs in subjects receiving 514G3 compared to those receiving placebo [(eight of 36 (22%) vs. seven of 16 (44%), respectively, (p=0.11)].
January 16, 2017
Synthetic Biologics reported results of a phase IIb study of SYN-004 (ribaxamase) designed to protect the gut microbiome from disruption caused by certain intravenous (IV) beta-lactam antibiotics. The study, a randomized, double-blind, placebo controlled trial of 412 patients, met its primary endpoint of significantly reducing C. difficile Infection (CDI). Preliminary analysis of the data indicated seven confirmed cases of CDI in the placebo group compared to two cases in the ribaxamase treatment group. Patients receiving ribaxamase achieved a 71.4% relative risk reduction (p=0.045) in CDI rates compared to patients receiving placebo. Adverse events reported during this trial were comparable between treatment and placebo arms. Preliminary analysis of the data demonstrated a significant reduction in new colonization by vancomycin-resistant enterococci (VRE) for patients receiving ribaxamase compared to placebo (p=0.0002). With agreement from the FDA, the study included a secondary endpoint to assess ribaxamase’s capacity to decrease the incidence of antibiotic-associated diarrhea from all causes. Preliminary analysis of the data suggested a trend toward such a reduction (p=0.13), which was due, for the most part, to the reduction of CDI. Synthetic Biologics is also continuing to prepare for the initiation of pivotal phase IIb/III clinical trials for SYN-010, designed to treat the underlying cause of irritable bowel syndrome with constipation (IBS-C).
November 28, 2016
RedHill Biopharma reported results of a phase III trial of RHB-105 for H. pylori infection. The study demonstrated an overall success rate of 89.4% in eradicating H. pylori, and met its protocol-defined primary endpoint of superiority in eradication of H. pylori infection over historical standard-of-care (SoC) efficacy levels of 70%, with high statistical significance (p<0.001). Subsequent open-label treatment with SoC therapies of patients in the placebo arm of the ERADICATE Hp study demonstrated only 63% eradication rate, further supporting the potential superior efficacy of RHB-105 over SoC. A confirmatory phase III study is planned to be initiated in the U.S. Additional studies may be required, subject to FDA feedback. RHB-105 has been granted Qualifying Infectious Disease Product (QIDP) designation by the FDA, providing a Fast Track development pathway, as well as NDA Priority Review status, potentially leading to a shorter NDA review time by the FDA, if filed.
July 11, 2016
The Medicines Company has announced phase III results of CARBAVANCE (meropenem-vaborbactam) for complicated urinary tract infection (cUTI). TANGO 1 was a multicenter, randomized, double-blind, double-dummy study to evaluate the efficacy, safety and tolerability of CARBAVANCE compared to piperacillin-tazobactam in the treatment of cUTI, including acute pyelonephritis, in adults. The trial enrolled 550 adult patients randomized 1:1 to receive CARBAVANCE (meropenem 2g-vaborbactam 2g) as a three-hour IV infusion every eight hours or piperacillin 4g-tazobactam 500mg as a 30 minute IV infusion every eight hours, each for up to 10 days. After a minimum of five days of IV therapy, patients who met protocol-defined criteria of improvement were transitioned to oral levofloxacin. For the FDA, the primary assessment was performed in the microbiologic modified intent-to-treat (mMITT) patient population, and was defined as overall success of clinical outcome (cure or improvement and microbiologic outcome of eradication (baseline bacterial pathogen reduced to <104 CFU/ml)). Overall success was observed in 188/192 patients (98.4%) in the meropenem-vaborbactam group and in 171/182 patients (94.0%) in the piperacillin-tazobactam group—a difference of 4.5% (95% CI: 0.7 % to 9.1%). For the EMA, the primary assessment was defined as microbiologic outcome of eradication (baseline bacterial pathogen reduced to <103 CFU/ml) at the test-of-cure (TOC) visit in the mMITT and microbiologic evaluable (ME) patient populations. For the mMITT patient population, the microbiological eradication was 128/192 patients (66.7%) in the meropenem-vaborbactam group and 105/182 patients (57.7%) in the piperacillin-tazobactam group—a difference of 9.0% (95% CI: -0.9% to 18.7%). For the ME patient population, the microbiological eradication was 118/178 patients (66.3%) in the meropenem-vaborbactam group and 102/169 patients (60.4%) in the piperacillin-tazobactam group—a difference of 5.9% (95% CI: -4.2% to 16%). The company believes that TANGO 1 provides the pivotal clinical data necessary for the submission of an NDA with the FDA and a marketing authorization application (MAA) with the EMA.
May 30, 2016
Pfizer released results of two phase III studies demonstrating the immunogenicity of TRUMENBA (Meningococcal Group B Vaccine) against invasive meningococcal B (MnB) strains representative of prevalent strains in the U.S. and Europe. One phase III study was a randomized, active-controlled, observer-blinded study that included approximately 3,600 healthy individuals 10 through 18 years of age. Individuals were randomized to receive one of three different lots of TRUMENBA in a zero, two, six-month schedule or a control, licensed hepatitis A (HAV) vaccine, at zero and six months and saline at two months. The hSBA responses one month after doses two and three against the four primary MnB test strains as defined by hSBA responses (titers ≥LLOQ) were 64.0%-99.1% and 87.1%-99.5%, respectively. As these four primary strains are representative, they predict the ability of antibodies elicited by TRUMENBA to be active against diverse circulating strains. The hSBA responses to the 10 additional MnB test strains were 61.1%-100.0% and 75.1%-98.6% one month after dose two and three, respectively. The second phase III study was a randomized, placebo-controlled, observer-blinded study that included approximately 3,300 healthy individuals 18 through 25 years of age. Individuals were randomized to receive TRUMENBA in a zero, two, six-month schedule or a saline control. The hSBA responses one month after dose two and three among TRUMENBA recipients against the four primary MnB test strains as defined by hSBA responses (titers ≥LLOQ) were 68.3%-97.4% and 87.4%-99.4%, respectively. The hSBA responses to the 10 additional MnB test strains were 51.6%-97.9% and 71.3%-99.3% one month after dose two and three, respectively. TRUMENBA is currently approved in the U.S. These data support additional upcoming global regulatory submissions and the planned U.S. supplement to request the conversion of Accelerated Approval to Traditional Approval for TRUMENBA.
March 28, 2016
RedHill Biopharma reported results from the first phase III clinical study with RHB-105 for the eradication of Helicobacter pylori (H. pylori). The randomized, placebo-controlled, ERADICATE Hp phase III study was intended to evaluate the safety and efficacy of RHB-105 as a first-line treatment for confirmed H. pylori bacterial infection. A total of 118 non-investigated dyspepsia patients with confirmed H. pylori infection were enrolled and treated in the study, which was conducted in the U.S. Subjects were randomized in a 2:1 ratio to receive either RHB-105 or a placebo for a period of 14 days and assessed for the eradication of H. pylori infection. Subsequent to completion of the treatment period and the un-blinding of the study, subjects enrolled in the placebo arm were entitled to receive SoC therapy as prescribed by the treating physician in an open-label setting, and were assessed for the eradication of H. pylori infection 28-35 days after completion of treatment. The study demonstrated an overall success rate of 89.4% in eradicating H. pylori, and met its protocol-defined primary endpoint of superiority in eradication of H. pylori infection over historical standard-of-care (SoC) efficacy levels of 70%, with high statistical significance (p<0.001). The final results demonstrated 89.4% efficacy in eradicating H. pylori infection with RHB-105 in all patients who received at least one dose of randomized study treatment and underwent a 13C UBT test of cure at Visit 4, 28-35 days after completion of treatment with RHB-105. Subsequent open-label treatment of patients in the placebo arm with SoC therapy for persistent H. pylori infection demonstrated a 63% eradication rate with SoC, further supporting the potential superior efficacy of RHB-105 over SoC. The safety profile of RHB-105 was consistent with that observed in the top-line analysis of the phase III study. RHB-105 was shown to be safe and well-tolerated, with the majority of treatment-related adverse events assessed as mild to moderate. Only one serious adverse event was recorded in the RHB-105 treatment group and was assessed as unrelated to the study drug. RedHill plans to conduct a confirmatory phase III study. Additional studies may be required, subject to FDA feedback. RHB-105 has been granted Qualifying Infectious Disease Product (QIDP) designation by the FDA, providing a Fast Track development pathway, as well as Priority Review status, potentially leading to a shorter review time by the FDA of an NDA, if filed.
February 22, 2016
Seres Therapeutics reported results of a phase Ib/II study of SER-109 in recurrent Clostridium difficile infection (CDI). The open-label, single arm, descending-dose study enrolled 30 patients with recurrent CDI at four medical centers in the U.S. All enrolled patients received standard-of-care antibiotic treatment, followed by oral administration of SER-109. Of the 30 study patients, 26 (87%) achieved the primary endpoint of absence of diarrhea with a positive C. difficile test up to eight weeks following dosing. Three of the four patients who did not meet the primary endpoint were determined by their primary investigator to be recovering from CDI, and all symptoms resolved without further therapeutic intervention or antibiotics. In total, 29 of 30 patients (97%) achieved full clinical cure of recurrent CDI following SER-109 administration. By contrast, the expected cure rates in people treated with the standard-of-care range from 23-31%, according to a recent well-controlled study SER-109 was well-tolerated in the study, with the most common adverse events being mild to moderate gastrointestinal symptoms. No drug related serious adverse events were observed.
November 23, 2015
MicuRx Pharmaceuticals has reported results of a phase II study of MRX-I for the treatment of drug-resistant bacteria such as MRSA and VRE. The double-blind study conducted at six sites in the U.S. enrolled a total of 120 patients with acute bacterial skin and skin structure infections (ABSSSI), each of whom received 10 days of treatment consisting of twice-daily oral administration of either 800mg of MRX-I (n=80 subjects) or linezolid (n=40). For the primary efficacy end point, 90% of patients (72/80) in the MRX-I group achieved early clinical response, compared to 87.5% of patients (35/40) in the linezolid group. MRX-I demonstrated a favorable safety and tolerability profile. No drug-related serious adverse events or discontinuation of the treatment due to adverse events were noted in MRX-I patients. The positive results are in line with those of the first phase II clinical study in complicated skin and soft tissue infections performed by MicuRx in China.
November 2, 2015
Melinta Therapeutics has released
results from phase II studies of delafloxacin
for acute bacterial skin and skin structure
infection (ABSSSI). In the double-blind,
phase II, multicenter study, 660 patients
with ABSSSIs were randomized to receive
either intravenous (IV) delafloxacin or
vancomycin plus aztreonam for five to14
days. Patients had wounds, burns, major
abscesses or cellulitis with lesions of at
least 75 cm2 in size (average lesion size was
307 cm2) and at least two systemic signs
of infection. Delafloxacin met the study’s
primary endpoint, reduction in lesion size by
at least 20% at 48-72 hours in the intent-to-treat
(ITT) population without non-study
antibiotics or major procedures, which was
comparable to the response in the control
arm receiving vancomycin plus aztreonam.
Delafloxacin also was comparable
to vancomycin+aztreonam in the study’s
secondary endpoint of cure, defined as the
complete resolution of signs and symptoms
at the follow-up visit (day 14). Melinta anticipates
filing an NDA with the FDA in 2016.
October 5, 2015
Merck has reported results of two pivotal
phase III clinical studies for bezlotoxumab,
its investigational antitoxin for prevention
of Clostridium difficile (C. difficile) infection
recurrence. MODIFY I and MODIFY II were
double-blind, placebo-controlled trials that
enrolled 1,452 and 1,203 patients, respectively.
The studies were conducted in both
hospital and outpatient settings, and the primary
endpoint for each study was evaluated
through 12 weeks following study drug administration.
In the MODIFY I study, patients
receiving standard-of-care antibiotics for C.
difficile were randomized to receive a single,
one-time infusion of either bezlotoxumab
(10mg/kg) (n=403), actoxumab (10mg/kg)
(n=242), the combination of bezlotoxumab
and actoxumab (10mg/kg each) (n=403) or
placebo (n=404). The actoxumab arm was
stopped for efficacy and safety reasons after
an interim analysis. In the MODIFY II study,
patients receiving standard-of-care antibiotics
for C. difficile were randomized to receive
a single, one-time infusion of either bezlotoxumab
(10mg/kg) (n=407), bezlotoxumab
and actoxumab (10mg/kg each) (n=397)
or placebo (n=399). In both trials, the rate
of C. difficile infection recurrence through
week 12, the primary efficacy endpoint, was
significantly lower in the bezlotoxumab arms
(17.4%, p=0.0003) and (15.7%; p=0.0003),
and the combination bezlotoxumab and actoxumab
arms (15.9%, p<0.0001) and (14.9%,
p<0.0001), compared to the placebo arms
(27.6%) and (25.7%), respectively. Based on
those results, the company plans to submit
New Drug Applications seeking regulatory
approval of bezlotoxumab in the U.S., E.U.
and Canada in 2015. Currently, there are no
therapies approved for the prevention of
recurrent disease caused by C. difficile.
September 21, 2015
RedHill Biopharma has reported results
of a phase III study of RHB-105 for eradication
of H. pylori. The randomized, placebo-controlled,
ERADICATE Hp phase III study
was intended to evaluate the safety and
efficacy of RHB-105 as a first-line treatment
for confirmed H. pylori bacterial infection.
A total of 118 non-investigated dyspepsia
patients with confirmed H. pylori infection
were enrolled and treated in the study,
which was conducted in the U.S. Subjects
were randomized in a 2:1 ratio to receive
either RHB-105 or a placebo for a period of
14 days and assessed for the eradication of
H. pylori infection. The study demonstrated
an overall success rate of 89.4% in eradicating
H. pylori, and met its protocol-defined
primary endpoint of superiority in eradication
of H. pylori infection over historical
standard-of-care efficacy levels of 70%,
with high statistical significance (p<0.001).
RedHill plans to conduct a second phase III
study. Additional studies may be required,
subject to FDA feedback. RHB-105 has been
granted Qualifying Infectious Disease Product
(QIDP) designation by the FDA.
May 11, 2015
Actavis issued results of a phase III study
of Dalvance for acute bacterial skin and skin
structure infections (ABSSSI) caused by susceptible
Gram-positive bacteria, including methicillin
resistant Staphylococcus aureus (MRSA).
The study was a randomized, double-blind,
double-dummy trial conducted in 698 patients
and compared a single 1500mg intravenous
(IV) dose of Dalvance to the approved regimen
of two-doses given one week apart (1000mg
IV on day one followed by 500mg IV on day
eight). 94.4% of patients in the single-dose
Dalvance arm and 94% of patients in the two-dose
Dalvance arm achieved clinical success at
day 14 (95% CI -3.5, 4.3). At day 28, 84.5% of patients
treated with a single-dose achieved clinical
success compared to 85.1% of those treated
with the two-dose regimen (95% CI -6.0, 4.8).
The 1500mg single-dose achieved its primary
endpoint of non-inferiority to the two-dose
regimen (10% non-inferiority margin) at 48-72
hours after initiation of therapy, as determined
by a decrease of >20% in lesion area relative
to the baseline measurement (81.4% v. 84.2%
for the single dose v. the two-dose regimen,
respectively; difference -2.9; 95% CI: -8.5, 2.8).
Actavis plans to file an sNDA with these data in
the third quarter.
April 29, 2013
ViroPharma issued results from a phase II trial of VP20621 for the treatment of C. difficile infections (CDI). This randomized, double-blind study enrolled 168 subjects with recurrent CDI. After completing antibiotic treatment, subjects received either placebo (n=43) or VP20621 doses of 104 spores QD (once per day) for seven days (n=41); 107 spores QD for seven days (n=43); or 107 spores QD for 14 days (n=41). Results showed the study met its primary endpoint—the detection of viable nontoxigenic C. difficile in stool culture, which was detected in 54% of subjects treated with the low dose of VP20621 and up to 79% of those receiving the high dose. In addition, across all dose groups, VP20621 reduced the incidence of CDI by ≥50% versus placebo, with a similar reduction in antibacterial treatment for CDI versus placebo in this study. The CDI recurrence rate was 2% in the subgroup of patients successfully colonized with VP20621. VP20621 was well tolerated. The most frequent adverse events were mild to moderate headache.
September 17, 2012
Tetraphase Pharmaceuticals released results from a phase II trial of eravacycline (TP-434) versus ertapenem for the treatment of infections caused by drug-resistant gram-negative pathogens. This randomized, double-blind, double-dummy study enrolled 143 patients: 75 with complicated appendicitis and 68 with other diagnoses. Subjects received eravacycline 1.5mg/kg intravenously once daily, eravacycline 1.0mg/kg intravenously,twice daily, or ertapenem 1g intravenously once daily. The results of the study show that eravacycline was highly active against drug-resistant bacterial pathogens, demonstrating infection cure rates similar to that of ertapenem. All treatment arms in the trial demonstrated cure rates in the ME population of between 93% and 100%. Both drugs were well tolerated. The most frequent adverse events were gastrointestinal side effects, although at very low rates.
April 30, 2012
PolyMedix issued results from a phase II trial of PMX-30063 for the treatment of acute bacterial skin and skin structure infections (ABSSSI) caused by Staphylococcus aureus. The randomized, double-blinded and controlled study enrolled 215 subjects with ABSSSI due to either methicillin susceptible (MSSA) or methicillin resistant (MRSA) S. aureus. The subjects received one of three dosing regimens of PMX-30063 or daptomycin active control. PMX-30063 was administered at 0.4 mg/kg on day one followed by 0.30 mg/kg daily for four days; 0.75 mg/kg on day one followed by 0.35 mg/kg daily for four days; or 1.0 mg/kg on day one followed by 0.35 mg/kg daily for four days plus two days of placebo for a total of seven days. Daptomycin was administered daily for seven days. Clinical and microbiologic response was assessed at 72 hours (Day 3). All three doses of PMX-30063 resulted in high clinical response rates at 72 hours. In the per protocol population the clinical response rates were 85.0%, 71.4%, 89.7% and 74.5% in the PMX-30063 low, medium and high dose arms and the daptomycin arm, respectively. The most commonly reported adverse events reported in the PMX-30063 treatment arms were numbness and tingling.
March 19, 2012
Foamix released results from a phase II trial of Minocycline foam for the treatment of impetigo. This randomized, double blind, dose-ranging study enrolled 32 subjects, ages 2 to 15, with impetigo. The subjects received Minocycline foam 1% or 4% twice daily for seven days. They were checked for response on day 14. Clinical response at the end of the treatment was 92% and 100% respectively for the low or high doses; and all subjects (100%) showed success on day 14. In addition, 80% of the total population were cured or improved significantly after three days of treatment. Eight subjects had MRSA and in all of them the bacterial infection was eradicated on day seven. No drug related side effects were reported.
December 19, 2011
Rib-X reported results from a phase IIb trial of delafloxacin for acute bacterial skin and skin structure infections. This randomized, active controlled, double blind trial enrolled 256 adults who received delafloxacin alone (300 mg intravenously every 12 hours), or Zyvox (linezolid) or vancomycin at the recommended doses, both with and without aztreonam. The trial met the primary endpoint, the Investigators Global Assessment of Cure. Clinical cure was reached by 70.4%, 64.9% and 54.1% of subjects in the delafloxacin, Zyvox plus/minus aztreonam and vancomycin plus/minus aztreonam arms, respectively, with statistical superiority in comparison to vancomycin (p≡0.031). In a group of subjects with confirmed MRSA, the clinical cure was reached by 59.3%, 51.5% and 56.3% of subjects in the three arms, respectively. Overall adverse event rates were statistically equivalent across the study arms.
December 12, 2011
Polymedix reported interim results from a phase II trial of PMX-30063 for the treatment of acute bacterial skin and skin structure infections (ABSSI). Data are from 80 subjects with ABSSSI due to either methicillin-susceptible or methicillin-resistant S. aureus. The subjects were randomized to receive either one of three five-day dose regimens of PMX-30063 or the standard of care, daptomycin, for the approved seven-day dose regimen. The combined data for all treatment arms showed a clinical cure rate of 92%, with each of the four dosing arms having clinical cure rates ranging from 87% to 100%. All dose groups were safe and generally well-tolerated.
September 19, 2011
Cempra issued results from a phase II trial of oral solithromycin (CEM-101) for the treatment of community-acquired bacterial pneumonia. This randomized, double-blind trial enrolled 132 subjects who received either CEM-101 (800 mg on day one followed by 400 mg on days two to five) or oral levofloxacin, the standard of care (750 mg on days one to five). The primary endpoint was continued improvement or complete resolution of baseline signs and symptoms at the Test of Cure visit, which was completed five to ten days after the last dose of the drug. CEM-101 demonstrated efficacy comparable to levofloxacin and a favorable safety and tolerability profile, with a lower incidence of treatment emergent adverse events than levofloxacin.
June 20, 2011
Aradigm reported results from a phase IIb trial of ARD-3100 (inhaled ciprofloxacin) for the treatment of non-cystic fibrosis bronchiectasis. This double-blind, placebo-controlled trial, ORBIT-1, enrolled 95 subjects who were randomized into four groups (3mL ARD-3100, 2mL ARD-3100 or matching placebo), and treated once-a-day for 28 days, followed by a 28 day off-treatment period. The primary endpoint, the mean change in Pseudomonas aeruginosa colony forming units per gram of sputum (CFUs) from baseline to day 28, was reached. There was a significant mean reduction (p<0.001) of 2.942 log10 CFUs in the 3mL ARD-3100 group and a significant mean reduction (p<0.001) of 3.842 log10 CFUs in the 2mL ARD-3100 group compared to placebo. Pooled placebo groups had a mean reduction of log10 CFUs of 0.437. There was no statistically significant difference between the 2 mL and 3 mL ARD-3100 doses. Adverse events were similar between the treatment arms.
May 30, 2011
StarPharma reported results from a phase II trial of VivaGel for the treatment of bacterial vaginosis. This double-blind, randomized, placebo controlled, dose-ranging study enrolled 132 women who received 0.5%, 1% or 3% gel or placebo gel administered vaginally for seven consecutive days. The primary endpoint was Clinical Cure as defined by no abnormal discharge. VivaGel 1% resulted in 74% of subjects achieving Clinical Cure two to five days after completion of therapy compared with 22% in the placebo group (P≡0.0002). This effect was sustained: two to three weeks after completion of therapy, 46% of subjects achieved Clinical Cure compared with 12% for the placebo (P≡0.006). In addition, unpleasant vaginal odor was cured in 78% of the VivaGel treated subjects. The incidence of adverse events was similar across all placebo gel and VivaGel groups.
April 25, 2011
Nabriva Therapeutics issued results from a phase II trial of BC-3781 for acute bacterial skin and skin structure infections. This double blind trial enrolled 210 subjects and was designed to compare BC-3781 to Vancomycin, the standard of care. The subjects received 100mg or 150mg of BC-3781 or 1,000mg Vancomycin intravenously twice-daily. Both doses of BC-3781 were comparable to Vancomycin in terms of clinical response: 90% and 89% of subjects treated with 100mg and150mg of BC-3781, respectively, and 92% of the subjects treated with Vancomycin. In addition, the early clinical response was assessed using a composite endpoint (cessation of spread of erythema with a lack of fever) at day three. This endpoint was reached by 83% and 86% of subjects in the 150 mg and 100mg BC-3781 arms, respectively and 80% of subjects in the Vancomycin arm. BC-3781 was well tolerated.
March 7, 2011
Immunitor released results from a phase II trial of their V5 oral immunotherapy for the treatment of tuberculosis (TB). This randomized, placebo controlled trial enrolled 120 subjects with refractory TB, including re-treated TB, multi-drug resistant TB and TB with HIV co-infection, who received an oral V5 tablet or placebo daily. After one month, 88% of subjects the V5 arm were sputum smear negative versus 18% in placebo arm. The high conversion rate in V5 arm was similar regardless of TB type. V5 also down-regulated TB-associated inflammation and was associated with improvement in weight gain. No serious adverse events were reported.
April 5, 2010
Polymedix released positive results from a phase Ib trial of PMX-30063 under investigation for the treatment of bacterial infections. This blinded, randomized, placebo-controlled, ascending, multiple-dose study enrolled 77 healthy subjects. The trial consisted of three parts, each of which utilized different dosing durations including every 12, 24 or 48 hours, over five or ten days, for a planned total of five to ten doses. Doses in each part ranged from 0.08 to 0.60 mg/kg per day. Data showed no difference in tolerability or dose-limiting effects when PMX-30063 was administered every 12 or 24 hours. The dose-limiting total dose for healthy subjects was 3.0 mg/kg (0.6 mg/kg every 24 hours or 0.3 mg/kg every 12 hours). Doses of PMX-30063 below the dose-limiting total daily dose killed methicillin-sensitive Staphylococcus aureus and methicillin-resistant Staphylococcus aureus in serum in blood samples drawn from the subjects in the study. There were no serious adverse events.
April 13, 2009
Bayer reported positive interim results from a phase II trial of moxifloxacin for the treatment of tuberculosis. This randomized, controlled study enrolled 170 subjects in Rio de Janeiro, Brazil. The subjects received moxifloxacin (400 mg) or ethambutol (Myambutol) at 15 to 20 mg/kg of body weight, both in combination with standard treatment (rifampin, pyrazinamide, and isoniazid), for a six-month treatment duration. The primary endpoint was the eight-week conversion rate. At eight weeks, the culture conversion to negative had occurred in 80% of the moxifloxacin group, compared with 63% in the ethambutol group (p≡0.03). Seven subjects (5%) relapsed, three in the moxifloxacin group and four in the control group. Treatment has been well tolerated to date.
February 2, 2009
Rib-X reported positive results from a phase II trial of delafloxacin for the treatment of complicated skin and skin structure infections (cSSSI). This double-blind study enrolled 150 subjects who were treated with delafloxacin dosed intravenously at 300 mg and 450 mg twice a day or tigecycline, the standard of care, for 5 to 14 days. Both doses of delafloxacin were as efficacious as tigecycline in treating the infection. The cSSSI cure rates for delafloxacin 300 mg BID and 450 mg BID were 97.2% and 92.5%, respectively, while the cure rate for tigecycline was 91.2%. The MIC90 (Minimum Inhibitory Concentration required to inhibit the growth of 90% of organisms) values for delafloxacin and tigecycline against all S. aureus isolates was 0.06 and 0.12 micrograms/mL, respectively. Delafloxacin's MIC90 values against all MRSA, including the quinolone-resistant MRSA strains, was also 0.06 micrograms/mL. Delafloxacin was safe and well tolerated. Overall treatment-related adverse events were lower in both the 300 mg and 450 mg dose groups compared to tigecycline. Based on the results, Rib-X plans to move forward with the development of delafloxacin.
July 28, 2008
Aradigm released positive results from a phase II trial of inhaled liposomal ciprofloxacin for the treatment of Pseudomonas Aeruginosa infections in patients with cystic fibrosis. This open-label study enrolled 22 subjects with cystic fibrosis in Australia and New Zealand. Following an antibiotic washout period, subjects received inhaled liposomal ciprofloxacin once daily for 14 consecutive days. Data are from 21 subjects who completed the study. The primary endpoint was the change from baseline in the sputum Pseudomonas Aeruginosa colony forming units (CFU), Pseudomonas CFU decreased by a mean 1.43 log over the 14-day treatment period (p less than 0.0001) . One week after treatment ended, Pseudomonas bacterial density in the lung was still reduced by 1.02 log CFU from the baseline without additional antibiotic use. Pulmonary function testing, as measured by the forced expiratory volume in one second (FEV1), showed a significant mean increase of 6.86 % from baseline after 14 days of treatment (p=0.04). The study drug was well tolerated, with no serious adverse events reported. Based on the results, Aradigm plans to advance the development of liposomal ciprofloxacin for cystic fibrosis into the United States.
June 30, 2008
Forest Labs released positive results from two phase III trials of ceftaroline for the treatment of complicated skin and skin structure infections (cSSSI). These international, randomized, double-blind comparative studies, dubbed CANVAS I and CANVAS II, enrolled 1,396 adult subjects with cSSSI caused by gram-positive and gram-negative bacteria. The primary endpoint was non-inferiority of ceftaroline compared to vancomycin plus aztreonam, with a non-inferiority margin of 10%. This endpoint was reached; the ceftaroline arm had a clinical cure rate of 91.6% compared to a 92.7% clinical cure rate in the vancomycin plus aztreonam arm. In addition, ceftaroline had a microbiological eradication rate of 92.4% compared to a vancomycin plus aztreonam rate of 93.6% for all pathogens. The ceftaroline clinical cure rate was 93.1% in Staphylococcus aureus infections in the microbiologically evaluable population and 93.3% for MRSA infections. Treatment was well tolerated, with an adverse events profile similar between the two treatment arms. Based on the results Forest plans to continue with the development of ceftaroline.
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.
December 3, 2007
NovaBay released positive results from a phase I trial of AgaNase for the treatment of bacterial and viral infections. This double-blind placebo controlled study enrolled ninety-six subjects. The subjects received repeated applications of AgaNase, using various concentrations (0.1% and 0.3%) and regimens, applied by spray or swab to the anterior nares. Treatment was well tolerated, with any adverse events local, mild, and transient. The incidence of adverse events did not increase with higher dose. There was no detectable systemic exposure of AgaNase or its major metabolite. Based on the results NovaBay plans to move forward with the development of AgaNase.
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.
September 3, 2007
Pharmaxis released positive results from a phase III trial of Bronchitol for the treatment of bronchietasis. This double-blind, placebo-controlled, parallel group study enrolled 362 subjects across Australia, New Zealand, United Kingdom, Northern Ireland. The subjects were randomized 2:1 to receive 320 mg of Bronchitol or placebo twice daily for 12 weeks. The trials primary endpoints, improvement in quality of life measures and mucus clearance versus placebo, were both achieved. At 12 weeks the subjects receiving Bronchitol showed a highly significant improvement in quality of life, as assessed by the St George Respiratory Questionnaire over placebo (p-value less than 0.05). In addition, mucous clearance at 12 weeks was also significantly improved over placebo (p-value less than 0.001). Treatment was well tolerated, with adverse events similar between the active and placebo groups. Pharmaxis filed a Special Protocol Assessment with the FDA for US phase III trial in August of 2007.
July 16, 2007
Theravance announced positive results from a phase II trial of TD-1792 for the treatment of complicated skin and skin structure infections (cSSSI) caused by Gram-positive bacteria. This randomized, double-blind, active-controlled trial enrolled 197 subjects who received either 2 mg/kg TD-1792 dosed once daily or vancomycin (standard of care) dosed 1 g twice daily for up to 14 days. Aztreonam and/or metronidazole were added for Gram-negative or anaerobic coverage. The primary endpoint, non-inferiority in clinical cure rates as measured at days 7 and 14, was achieved. In the clinically evaluable population, the clinical cure rates were 91.7% for the subjects treated with TD-1792 and 90.7% for the subjects treated with vancomycin. The clinical cure rates for the subjects with methicillin-resistant Staphylococcus aureus (MRSA) infections were 94.7% for the TD-1792 arm and 91.9% in the vancomycin arm. In the all-treated population, the clinical cure rates were 80.6% and 82.8% in the TD-1792 and vancomycin groups, respectively. Of the microbiologically evaluable subjects, the clinical cure rates for TD-1792 and vancomycin were 93.7% and 92.1%, respectively. Based on the results, Theravance plans to evaluate higher doses of TD-1792 in further trials.
July 2, 2007
Replidyne released positive results from three phase I trials of REP8839 for the treatment of bacterial skin and wound infections. A total of 400 subjects were enrolled in the trials. In the first study, subjects received repeated daily applications of REP8839 at three concentrations (1%, 2% and 4%), on intact and abraded skin. Safety, tolerability and skin irritancy were tested. Irritancy scores comparable to placebo were recorded for all REP8839 exposed test subjects. In the second study, subjects received repeated daily application of REP8839 on a larger surface area of intact and abraded skin. In addition to safety, tolerability and dermal irritancy, systemic exposure was evaluated. In all subjects, REP8839 was associated with low systemic exposure and low skin irritancy. In the third study, a 2% formulation of REP8839 was evaluated for its’ ability to cause long-term sensitization and irritancy. No sensitization reactions were recorded and low irritancy potential was observed. No serious adverse events occurred in any of the three trials. Based on the results, Replidyne plans to initiate a phase II trial of REP8839 for the treatment of impetigo in pediatrics by the end of 2007.
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.
December 4, 2006
Arpida reported positive results from a phase III trial, dubbed ASSIST-1, of iclaprim for the treatment of skin and skin structure infections (cSSSI). The trial was designed to compare iclaprim to linezolid, a previously approved treatment. This international, randomized, double-blind trial enrolled 497 subjects with cSSSI. Subjects were assigned (1:1) to receive intravenous iclaprim (0.8 mg/kg) or intravenous linezolid (600mg) for 10 to 14 days and were evaluated during treatment. The Test-Of-Cure visit took place 7-14 days after the end of treatment. Treatment was well tolerated with no serious adverse events reported. The primary endpoint, statistical non-inferiority in the clinical cure rate at the Test-Of-Cure (TOC) visit, was reached. The overall clinical cure rates for the Intent-To-Treat population of 497 subjects, were 85.5% and 91.9% for iclaprim and linezolid, respectively. For the clinically evaluable subjects, the cure rates were 93.8% and 99.1% for iclaprim and linezolid, respectively. A similar phase III trial, ASSIST-2, is currently underway. Arpida plans to file a NDA with the FDA in 2007.
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.
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.
VaxGen reported positive results from a phase I trial of rPA102, the company's anthrax vaccine candidate. This randomized, double-blinded, controlled, multicenter trial enrolled subjects who received rPA102, in varying doses, four weeks apart. It was designed to demonstrate a clear relationship between the rPA102 dose administered and the subsequent immune response. Safety data were positive with no serious adverse events or toxicities reported. Efficacy data were also positive with higher antibody titers seen in subjects who received three injections of the vaccination versus those who received two injections. Based on these results, Vaxgen planned further development of this drug.
October 17, 2005
Oscient Pharmaceuticals has announced positive results of phase III trials of Factive (gemifloxacin mesylate) tablets, for the treatment of acute bacterial sinusitis (ABS) and acute bacterial exacerbations of chronic bronchitis (AECB). Pooled retrospective results from their phase III ABS program indicated that Factive was significantly superiority to approved therapies (cefuroxime and trovafloxacin) in both clinical success at end of therapy (89.3% vs. 77%; p=0.01) and in clinical success at follow-up (79.9% vs. 66.3%; p=0.019). Pooled data from the company's 10 AECB trials indicated non-inferiority of clinical response compared to a number of approved therapies (including clarithromycin, levofloxacin, trovafloxacin, amoxicillin-clavulanate, ceftriaxone/cefuroxime and ofloxacin). Factive is currently approved to treat AECB and community-acquired pneumonia; in is still under investigation for ABS.
September 5, 2005
Eisai reported results of a phase II trial of eritoran (E5564), their Toll-like receptor 4 antagonist for the treatment of severe sepsis. Results from the study yielded a positive trend towards decreasing mortality risk in the higher dose group to 22.4% (p=0.09), compared to 32.5% in the low dose group and 22.4% in the high dose group. Among the most high risk subjects, the high dose group had a mortality risk of 33.3% (p=0.07), and the low dose group had a risk of 37.9% (p=0.17), compared to 50.9% for placebo. This placebo-controlled study enrolled 293 patients in North America, who received either low dose (45 mg) or high dose (105 mg) eritoran or placebo twice daily for 6 days. Based on these results, the company announced plans to initiate phase III development of the drug in the US, Canada and Europe.
Emergent BioSolutions reported positive results of a phase II trial of their investigational oral typhoid vaccine, for the prevention of Salmonella typhi infections. Trial data indicated that a simple rapid dosing regimen did not negatively impact safety or immunogenicity levels, compared to an earlier regimen which required preloading with a bicarbonate buffer and a restricted reconstitution process. Both formulations were highly immunogenic, producing response deemed appropriate for clinical and commercial use. This open-label study enrolled 32 healthy subjects, who received single oral doses of either the older lyophilized formulation or Emergent's investigational vaccine. Following these results, the company announced plans to conduct additional phase II trials of the drug in Vietnam, prior to initiating phase III development.
NexMed has issued positive results of a phase I trial of their investigational antifungal nail lacquer NM100060 (NexACT terbinafine), for the treatment of onychomycosis (nail fungal infections). Pharmacokinetic data indicated that lacquer application of the drug produced peak plasma concentrations approximately 2500% less that a single oral dose of terbinafine, and comparable levels to an approved terbinafine cream. Target drug concentrations in nail clippings were achieved by mid-way through the treatment period. Safety data yielded no reported serious adverse events; the most common overall adverse event was minor local irritation. This double-blind, randomized, parallel-design, placebo controlled study enrolled 56 patients, who received treatment with NM100060, an approved 1% terbinafine cream, and and a single 250 mg terbinafine oral tablet. The company announced that they had initiated licensing discussions for the drug.
July 25, 2005
Human Genome Sciences reported positive results of a phase I study of ABthrax, for the prevention of Anthrax infections. Primary safety endpoints were met, with no serious or dose-limiting adverse events reported. Overall adverse events were generally mild and transient, with no statistical difference in the rate of events between ABthrax and placebo. Pharmacokinetic data indicated good bioavailability, and a mean elimination half-life of 15-19 days. Biological activity was dose-dependent, and serum concentrations achieved levels predicted to be protective against anthrax infection. This randomized, single-blind, placebo-controlled, dose- escalation study enrolled 105 healthy subjects, who received one of three doses of ABthrax via intramuscular injection (0.3 mg/kg, 1.0 mg/kg and 3.0 mg/kg), one of five doses of the drug via intravenous infusion (1.0 mg/kg, 3.0 mg/kg, 10.0 mg/kg, 20.0 mg/kg and 40.0 mg/kg), or placebo.
July 18, 2005
Nabi Biopharmaceuticals reported positive results of an ongoing phase IIb study of their investigational Staphylococcus aureus vaccine StaphVAX. Trial data yielded positive immunogenicity results, with substantial increases in serum antibody levels by day 7, and 93% of subjects demonstrating antibody concentrations at or above estimated protective levels by day 14, a rate higher than that observed in previous studies of the drug in patients with end- stage renal disease. Safety data were also positive, with no serious adverse events reported and mild, transient overall adverse event incidence. This double-blind study enrolled 120 patients undergoing cardiovascular surgical procedures across 15 sites in the US, who received a single treatment with the vaccine prior to surgery with 14 day immunological observation. The trial is currently in a 6-month open-label follow-up.
June 20, 2005
Advancis and Par have issued negative results of a phase III trial of their investigational antibiotic Amoxicillin PULSYS, for the treatment of Group A streptococcal pharyngitis/tonsillitis. Trial data failed to meet their primary non-inferiority endpoint, with 76.6% of patients achieving bacterial eradication at the end of treatment, compared to 88.5% of subjects receiving penicillin. Secondary non-inferiority endpoints were also missed, including clinical cure at the test-of-cure visit and bacterial eradication at the late post-therapy visit. This open-label study enrolled 353 patients, who received either 775 mg Amoxycillin PULSYS once-daily for seven days or 250 mg penicillin VK four times daily for ten day. The companies anticipate that these results will delay NDA filing by at least 1 year.
May 16, 2005
Vertex Pharmaceuticals issued interim results of a phase Ib trial of VX-950, their investigational protease inhibitor for the treatment of hepatitis C virus (HCV) infections. Data from the ongoing study indicated that the drug yielded significant antiviral activity, with subjects experiencing a median reduction in genome 1 HCV RNA of greater than 3 log10 within three days of treatment; subjects receiving 750 mg thrice daily achieving an additional median reduction greater than 4 log10 over days 3-14. This double-blind, randomized, placebo-controlled study enrolled 34 HCV patients across 3 European sites, and was designed to investigate the tolerability, pharmacokinetics, effect on viral kinetics, and optimum dosing regimen of the drug. Subjects received one of 3 oral doses of VX-950 (450 mg or 750 mg every 8 hours, or 1250 mg every 12 hours) or placebo for 14 days. The company announced plans to release more detailed results at the Digestive Disease Week conference on May 17.
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 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.<
August 23, 2004
Vicuron Pharmaceuticals has issued the results from three pivotal phase III studies of dalbavancin, their semi-synthetic glycopeptide A-40926 derivative for the treatment of skin and soft tissue infections (SSTIs) caused by gram-positive bacteria. Each of the three studies, which investigated dalbavancin in differing SSTIs, met their primary endpoint of non-inferiority in clinical response, including in the intent-to-treat population, when compared to the approved therapies of linezolid, cefazolin, and vancomycin. The first study, a randomized, double-blind, approved-drug-controlled study of dalbavancin vs. linezolid, enrolled 854 subjects with complicated SSTIs; the second study, a randomized, double-blind, approved-drug-controlled study of dalbavancin vs. cefazolin, enrolled 565 subjects with uncomplicated SSTIs; the third study, a randomized, open label, approved-drug-controlled study of dalbavancin vs. vancomycin, enrolled 156 subjects with SSTIs caused by methycillin-resistant Staphylococcus aureus. Dalbavancin was well tolerated in all three studies. Vicuron announced plans to submit an NDA to the FDA based on these results.
May 17, 2004
Genzyme reported positive results from a phase II trial investigating tolevamer sodium, an investigational polymer therapy for the treatment of Clostridium difficile associated diarrhea. The primary endpoint was non-inferiority to vancomycin with respect to time to resolution of diarrhea. Data demonstrated that tolevamer met the non- inferiority endpoint at the six gram dose level. In addition, tolevamer was found to be similar to vancomycin in median days to resolution of diarrhea. The randomized, double-blind, active-controlled study enrolled 300 subjects at 58 sites in the U.S., Canada and the UK. It was designed to determine the safety and effectiveness of tolevamer at two dose levels (6-3 g per day), versus an oral dose of vancomycin. Results were reported at the European Congress of Clinical Microbiology and Infectious Diseases meeting in Prague. Based on these results, Genzyme is now planning phase III trials to begin in early 2005.
Hemispherx Biopharma reported positive results from a phase III trial investigating Ampligen, an immunomodulator and antiviral drug for the treatment of Chronic Fatigue Syndrome (CFS). Results demonstrated a statistically significant increase in physical performance as measured by Treadmill Exercise Tolerance Testing compared with placebo, the study’s primary endpoint. Data showed that subjects on Ampligen had an improved exercise treadmill performance of 19.4% compared with 5.1% for subjects given placebo. The multi-center, double-blind, randomized, placebo-controlled pivotal study enrolled 234 subjects with CFS at 12 sites in the U.S. The study was designed to test the efficacy and safety of Ampligen at 400 mg twice weekly for 40 weeks. Results were reported at the 17th International Conference on Antiviral Research in Tucson, Arizona.
Vicuron Pharmaceuticals reported positive results from a phase II trial investigating dalbavancin, an injectable glycopeptide antibiotic for the treatment of catheter-related bloodstream infections (CR-BSI). The primary endpoint showed an overall response rate of 87% in dalbavancin treated subjects compared with 50% in those treated twice daily with vancomycin. The randomized, comparative, open-label study enrolled 67 subjects with CR-BSI in North America. Subjects received two doses of dalbavancin one week apart or vancomycin twice daily for 14 days. The primary endpoint was based on a composite of clinical and microbiological responses measured at 21 days after treatment. Results were reported at the 14th annual European Congress of Clinical Microbiology and Infectious Diseases meeting in Prague.
July 28, 2003
Micrologix and Fujisawa Healthcare reported negative results from a phase III trial investigating MBI 226 for the prevention of central venous catheter-related bloodstream infections. Results showed that the rate of bloodstream infections treated with MBI 226 (2.2%) failed to decrease significantly compared with standard iodine (2.6%). The primary objective of the trial was to demonstrate that MBI 226, administered at central venous catheter insertion sites, was superior to povidone iodine in preventing bloodstream infections. However, MBI 226 did demonstrate statistically significant superiority in preventing catheter colonization, one of the secondary endpoints in the study. Data confirmed a catheter colonization rate of 31% in the MBI 226 group as compared with 40% in the povidone iodine group. The multicenter, randomized study enrolled 1452 subjects. No serious adverse events related to the use of MBI 226 were reported.
October 7, 2002
Results of a phase II trial suggested that SCV-07 significantly increased the rate by which tuberculosis subjects became noncontagious. In the study, 80% (35/44) of tuberculosis subjects who underwent standard anti-TB chemotherapy were no longer contagious (measured by negative sputum cultures) three months after also receiving a five-day regimen of parenteral SCV-07 therapy. 37% (10/27) of subjects whose therapy did not include SCV-07 were no longer contagious. All the subjects receiving SCV-07 reported an improvement in symptoms including fever and cough. There was also a significant decrease in the number of subjects with lung damage. SCV-07 is a product of Sciclone Pharmaceuticals.
February 11, 2002
Positive late-stage trial results were reported for Sequella's Transdermal Patch for Active Tuberculosis (TB), a diagnostic that appears to distinguish between active infectious TB, latent TB and prior TB vaccination. In the trial, the Transdermal Patch demonstrated a sensitivity of 88%, an efficacy of 93% and a specificity of 100%. Additionally, 43 out of 49 subjects with active TB had a positive reaction to the TB patch, and there were no false positives in the control population. By comparison, all control and active TB subjects had positive Mantoux skin test results.