May 23, 2016
Melinta Therapeutics has released results a phase III study of Baxdela (delafloxacin) for acute bacterial skin and skin structure infections (ABSSSI). The pivotal study, the second of a phase III program, was a randomized, double-blind study. Patients in the Baxdela arm received 300mg of intravenous (IV) Baxdela every 12 hours for six doses followed by 450mg oral Baxdela every 12 hours. The recommended vancomycin dose was 15mg/kg of IV vancomycin every 12 hours based on actual body weight plus 1-2g of IV aztreonam every 12 hours. Duration of treatment in either the Baxdela or active control arms was 5-14 days. In the intent-to-treat population (ITT), IV-to-oral Baxdela met the FDA’s primary endpoint of statistical non-inferiority (10% non-inferiority margin) at the early clinical response at 48-72 hours after initiation of therapy (83.7%) compared to IV vancomycin combination therapy with aztreonam (80.6%). The 95% confidence interval for the treatment difference had lower and upper bounds of -2% and 8.3%, respectively. Baxdela also met the EMA’s required endpoint of statistical non-inferiority (57.7%) compared to vancomycin plus aztreonam (59.7%) based on the investigator’s assessment of complete cure (resolution of all baseline signs and symptoms) at the follow up visit in the ITT population. Lower and upper bounds of the 95% confidence interval for the treatment difference were -8.6% and 4.6%, respectively. In addition, Baxdela was comparable to vancomycin plus aztreonam in achieving treatment success at follow up (cure or improved, with no further antibiotics needed) with success rate of 87.2% v. 84.8%, respectively. IV/oral Baxdela monotherapy successfully eradicated Gram-positive pathogens, including MRSA, and Gram-negative pathogens at rates comparable to IV vancomycin/aztreonam combination treatment. Both IV and oral Baxdela were well-tolerated in the study participants. The company anticipates submitting an NDA to the FDA in the second half of this year.
March 14, 2016
Brickell Biotech released results of a phase IIb study of BBI-4000 (sofpironium bromide) for the topical treatment of primary axillary hyperhidrosis. The multicenter, randomized, double blind, placebo-controlled study three concentrations of BBI-4000 versus vehicle (placebo gel) in 189 people with primary axillary hyperhidrosis. Study participants were randomized to apply either 5%, 10% or 15% of BBI-4000 or placebo gel to their underarms once daily for 28 days. At baseline, all subjects had Hyperhidrosis Disease Severity Scale (HDSS) scores of 3 or 4 (scale, 1-4) and =50mg/5min sweat per axilla (underarm). Results showed BBI-4000 met its primary endpoint (ITT analysis) by successfully achieving a statistically significant 2-grade improvement in the HDSS, in a dose-related fashion. At the maximum dose (15%), 38.3% of participants improved more than 2 points on HDSS at day 29 versus 12.2% with vehicle (p<0.01). Additionally, BBI-4000 achieved a statistically significant 1- and 2-grade improvement in a newly developed patient reported outcome measure, the Hyperhidrosis Disease Severity Measure Axillary (HDSM-Ax). Using this measure (ITT analysis), 44.7% achieved a greater than 2-point improvement at day 29 in the 15% treatment group versus 19.5% for vehicle (p=0.01), while 72.3% for the 15% treatment group versus 43.9% vehicle achieved a greater than 1-point improvement (p=0.01). BBI-4000 was well-tolerated at all three concentrations studied.
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.
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.
May 20, 2013
Creabilis released results from a phase IIb trial of CT327 for the treatment of chronic pruritus in psoriasis. This randomized, double-blind, placebo-controlled study enrolled 160 patients with chronic pruritus in psoriasis. Subjects received CT327 ointment at 0.05%, 0.1% and 0.5% administered twice daily for eight weeks. Data demonstrated patients receiving CT327 showed a statistically significant and clinically meaningful reduction in pruritus compared to blinded placebo vehicle. Pruritus was measured using a visual analogue scale (VAS), the accepted regulatory endpoint. The reduction from baseline in pruritus VAS reached 60% for CT327 compared to 20% for vehicle alone (p<0.05). A clinically meaningful reduction in pruritus (VAS=20mm) was seen in up to 79% of patients for CT327 compared to 36% for vehicle alone (p<0.05). At baseline, 69% of patients reported at least moderate pruritus (VAS>40mm). An improvement was also seen in the CT327 treated groups versus vehicle in mPASI (modified Psoriasis Area and Severity Index) in all subjects. The drug was safe and well tolerated. Subjects receiving CT327 reported fewer adverse events and withdrawals due to pruritus than the vehicle treated patients.
Idera Pharmaceuticals reported results from a phase II trial of IMO-3100 for the treatment of plaque psoriasis. This randomized, double-blind, placebo-controlled study enrolled 44 patients with moderate to severe plaque psoriasis. Subjects received 0.16mg/kg or 0.32mg/kg or IMO-3100, or placebo, by subcutaneous injection once weekly for four weeks, with a follow-up period through day 57. Results showed on day 57, 48% of patients treated with either dose of IMO-3100 demonstrated statistically significant improvements of 35% to 90% from baseline Psoriasis Area Severity Index (PASI) scores compared with 0 in the placebo cohort (p<0.005). Additionally, analysis of biopsy samples collected from patients during the trial indicated PASI score improvements were associated with significant improvement of psoriasis disease-associated gene profile, including down regulation of activated genes in the IL-17 pathway,which is central to the pathogenesis of psoriasis. IMO-3100 was well tolerated at both dose levels. Based on these data, Idera Pharmaceuticals is planning a 12-week phase II trial of IMO-8400 in psoriasis to initiate in the second half of 2013.
March 11, 2013
Sanofi and Regeneron Pharmaceuticals issued pooled results from two phase Ib trials of dupilumab for atopic dermatitis. The trials enrolled a total of 67 subjects with moderate-to-severe atopic dermatitis not adequately controlled with topical medications. The subjects were randomized to three different doses of dupilumab (75mg, 150mg or 300mg) or placebo administered as weekly subcutaneous injections for four weeks. The efficacy data showed treatment with dupilumab at either 150mg or 300mg per week significantly improved the signs and symptoms of atopic dermatitis, with significant improvements in body surface area (BSA) score, Investigator Global Assessment (IGA) score and Eczema Area Severity Index (EASI) from baseline to week four, compared to placebo (p<0.05 vs. placebo for all measures and doses). The significant improvements in BSA, IGA and EASI scores were maintained at week eight in the 300mg dose group (p<0.05 vs. placebo). The most common adverse events were nasopharyngitis and headaches. A phase IIa trial is currently underway and a phase IIb trial is planned for later this year.
March 4, 2013
Novartis reported results from a phase III trial of omalizumab for the treatment of chronic idiopathic urticaria (CIU). This global, multi-center, randomized, double-blind, placebo-controlled study, ASTERIA II, enrolled 323 patients with moderate to severe CIU who remained symptomatic despite treatment with approved antihistamine doses. Subjects received omalizumab 75mg, 150mg or 300mg, or placebo, administered subcutaneously every four weeks, for a total of three doses within a 12-week treatment period, with a 16-week follow-up period. The study met its primary endpoint, showing that omalizumab given at doses of 150mg and 300mg led to significant improvement from baseline at Week 12 in the mean weekly ISS from baseline (approximately 14 in all treatment groups) by 8.1 (p=0.001) and 9.8 (p<0.001), respectively, compared to a 5.1 improvement in patients on placebo. The omalizumab 75mg dose group did not demonstrate statistical significance compared to placebo for the primary endpoint. All eight pre-specified secondary endpoints in the ASTERIA II trial were met for the 150mg and 300mg doses. Omalizumab was well tolerated. The more frequent adverse events were nasopharyngitis, idiopathic urticaria and headache. Novartis regulatory submissions are on track for 2013.
January 21, 2013
XOMA released interim results from a phase II trial of gevokizumab for the treatment of inflammatory facial lesions. This double-blinded, randomized, placebo-controlled study enrolled 92 patients with inflammatory facial lesions due to moderate to severe acne vulgaris. Subjects received gevokizumab 0.2mg/kg or 0.6mg/kg once a month, or placebo, for three months. Data demonstrated the 0.6mg/kg dose group showed a statistically significant reduction of 19 mean inflammatory lesions on Day 42 compared to a reduction of 13 lesions in the placebo treated group (p=0.077). Each of the groups had a mean baseline of approximately 31 inflammatory lesions. The magnitude of the difference was substantially maintained throughout the study, but differences at later measurement points were not statistically significant. The 0.6mg/kg dose group demonstrated both a clinically and statistically significant improvement in the Investigator Global Assessment (IGA) at Day 84, showing a 31% responder rate versus a 5% responder rate in the placebo group (p=0.031). The 0.2mg/kg dose group showed no clinically or statistically significant differences from placebo at any time point in inflammatory lesion count or in IGA. Gevokizumab was well tolerated. The incidence of adverse events was comparable between both active groups and placebo. Based on these data, XOMA will complete the study and then expect to follow non-infectious uveitis into phase III development with its partner, Servier.
October 8, 2012
Novartis reported results from a phase II trial of AIN457 (secukinumab) for the treatment of plaque psoriasis. This double-blind, parallel group, placebo-controlled study enrolled 404 patients with moderate to severe psoriasis on the hands, feet and nails. Subjects received AIN457 or placebo once-weekly for four weeks, with an analysic period at 12 weeks. Data showed AIN457 was nearly three times more effective than placebo at reducing plaque psoriasis (54.3% of patients versus 19.2% respectively, p=0.005), as measured by the Investigator’s Global Assessment (IGA). Patients also benefited if they received AIN457 once every four weeks, with 39.0% experiencing either “clear” or “minimal” psoriasis after 12 weeks of treatment. In this same treatment group, significantly more patients experienced improvements in pain and discomfort compared to placebo (36.2% versus -1.5%) from baseline; and in anxiety and depression versus placebo (16.3% versus 6.2%), as measured by EuroQol (EQ-5D). AIN457 was well tolerated. The most frequent adverse events were infections. Novartis will await the results of a large-scale and longer-term phase III study, expected in 2013, before submitting an NDA.
September 24, 2012
DUSA Pharmaceuticals issued results from a phase II trial of Levulan, Kerastick and BLU-U with or without occlusion versus vehicle for the treatment of actinic keratoses (AKs). This multi-center, blinded, randomized, vehicle-controlled study enrolled 70 patients with minimally to moderately thick AKs on the upper extremities. Subjects received Levulan, Kerastick and BLU-U or vehicle, with or without occlusion, for three-hour incubation periods. The study showed a statistically significant lesion reduction and complete clearance of AK of the extremities when compared to treatment with vehicle. At 12 weeks following PDT, the subjects treated with Levulan plus occlusion regimen demonstrated an 89% (p<0.0001) AK lesion clearance rate as compared to a 70% (p<0.0001) clearance rate for those treated without occlusion after up to two PDT treatments; subjects receiving vehicle plus occlusion and vehicle alone demonstrated 17% and 6% lesion clearance rates, respectively. The safety profile was similar to that seen in the current labeling. DUSA will use the data, in combination with anticipated phase II results from another trial, to form the basis for label expansion.
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.
November 7, 2011
Clinuvel reported results from a phase II trial of afamelanotide for the treatment of Erythropoietic Protoporphyria (EPP). The randomized, double-blind, placebo-controlled study (CUV030) enrolled 77 subjects, 68 of whom completed the trial. The subjects were administered either the afamelanotide implant or placebo at the start of study, after 60 days and 120 days, and were followed up to 180 days. The primary endpoint was to determine whether afamelanotide implants can reduce the severity of phototoxic reactions associated with EPP. Based on analysis of time spent outside, afamelanotide was shown to increase subjects ability to expose their skin to direct sunlight compared to placebo. The subjects who received afamelanotide spent significantly more time in direct sunlight between the most intense hours of 10 AM and 3 PM (p≡0.036) and between 10 AM and 8 PM (p≡0.025). Data from an EPP-specific quality of life assessment also demonstrated an improvement from baseline for subjects receiving afamelanotide compared to placebo at 60 days (p≡0.001), 120 days (p≡0.003) and 180 days (p<0.001). The afamelanotide implant was safe and well-tolerated.
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.
June 15, 2009
Trius reported positive results from a phase II trial of oral torezolid for the treatment of severe complicated skin and skin structure infections (cSSSI). This randomized, double-blind, dose-ranging study enrolled 188 subjects with cSSSI caused by gram-positive bacteria. Torezolid was administered orally at doses of 200, 300 or 400 mg once-daily for five to seven days. Of the 188 enrolled subjects, 164 were clinically evaluable at the test-of-cure visit. The overall cure rates for severe abscesses, cellulitis and wound infections were 96%, 97% and 90%, respectively. Clinical cure rates by dose in the evaluable population were 98%, 94% and 94% for the 200, 300 and 400 mg doses, respectively. In the group of microbiologically evaluable subjects, clinical cure was achieved in 100%, 93% and 96% of the 200, 300 or 400 mg dose groups, respectively. Torezolid was well tolerated.
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.
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.
June 23, 2008
Avontec issued positive results from a phase I study of AVT-02 UE for the treatment of inflammatory skin diseases. This randomized, double-blind, placebo-controlled study enrolled 20 healthy male subjects. The subjects received AVT-02 UE ointment applied topically twice a day for 28 days. The tolerability of AVT-02 UE was rated separately by the investigator and the subject on a five point scale ranging from 1=very good to 5=very poor. At all visits, the tolerability at each test area of both active and placebo was rated as either "good" or "very good". No substantial changes in laboratory values or skin physiology parameters, including transepidermal water loss, corneometry, sebumetry and measurement of the melanin and hemoglobin content, were found throughout the study. Pharmacokinetic assessment revealed that treatment with AVT-02 UE ointment was not associated with measurable blood concentrations of the active ingredient. Treatment was well tolerated, with no serious adverse events. A phase IIa trial is currently underway for the potential treatment of psoriasis.
January 21, 2008
Amgen and Wyeth issued positive results from a phase III trial of Enbrel for the treatment of moderate to severe plaque psoriasis in children and adolescents. This trial enrolled two hundred and eleven pediatric subjects with psoriasis who were initially randomized to receive twelve once-weekly weight-based doses of Enbrel (0.8 mg/kg up to the intended dose of 50 mg) or placebo. After this double-blind portion, two hundred and eight subjects entered a twenty four-week period of open-label Enbrel treatment once-weekly. At week thirty six, one hundred and thirty eight subjects were re-randomized to receive either Enbrel or placebo, to investigate withdrawal and re-treatment. The primary endpoint was at least a 75% improvement on the Psoriasis Area and Severity Index (PASI 75) at week twelve. After twelve weeks, the conclusion of the double-blind, placebo-controlled portion of the study, 57% of the subjects treated with Enbrel achieved PASI 75, compared with 11% of those treated with placebo (p less than 0.001). After twenty four weeks of open-label treatment, during which all subjects received Enbrel, PASI 75 was achieved by 68% of the subjects initially treated with Enbrel from the start of the study and 65% of those who initially received placebo. At the conclusion of the open-label treatment period (week thirty six), one hundred and thirty eight subjects were re-randomized to receive either Enbrel or placebo. During this period, the subjects who lost PASI 75 were re-treated. No rebounds or changes in the type of psoriasis were reported. Based on the results, Amgen filed a sBLA with the FDA for the use of Enbrel in this population.
CollaGenex reported positive results from a phase IV trial of Oracea for the treatment of rosacea. This prospectively randomized, double-blinded, placebo-controlled clinical study enrolled ninety one subjects in the US. The subjects were treated once daily with either doxycycline (100 mg) or Oracea (40 mg doxycycline, controlled release), both as an adjunct to topical MetroGel 1%, for sixteen weeks. Efficacy and adverse events were evaluated at baseline and at weeks four, eight, twelve and sixteen. The objective of the study was to demonstrate that increasing the dose of doxycycline above the anti-inflammatory levels provided by Oracea does not provide any additional benefit but significantly adds to the adverse event profile. The primary endpoint was the mean change in total inflammatory lesion count from baseline to the week sixteen. The subjects in the Oracea arm had an average of 19.8 inflammatory lesions at baseline and experienced a decrease in lesion count of 12.5 lesions, compared with 17.7 lesions at baseline and a decrease of 12.2 lesions in the doxycycline, 100 mg group. In addition, there were no differences observed between the treatment groups regarding the secondary endpoints of Investigators Global Assessment and Clinician's Erythema Assessment with (p-values of 0.86 and 0.50, respectively). A clear difference in the incidence of adverse events, primarily gastrointestinal reactions, was observed between the treatment groups. Nausea, vomiting, diarrhea and stomach discomfort were observed in 26% of subjects administered 100 mg of doxycycline versus only 5% in the Oracea group. Oracea is currently under investigation for the treatment of periodontal disease.
September 17, 2007
Moberg Derma issued positive results from a phase II trial of K301 for the treatment of seborrheic dermatitis of the scalp. This randomized, double-blind, placebo-controlled study enrolled 98 subjects in Sweden. Subjects received placebo or one of two doses of K301 applied topically once daily for the first four weeks followed by four weeks of maintenance treatment. The primary endpoint was the degree of erythema and desquamation after four weeks. Results demonstrated that 76% of subjects who received the most efficacious formulation of K301 had a positive response to the treatment, compared to 40% for placebo. Treatment was well tolerated, with adverse events similar to placebo. Based on the results Moberg plans to initiate a phase III trial of K301 in Q4 of 2007.
July 23, 2007
Arpida reported positive results from a phase III trial, dubbed ASSIST-2 (Arpida Skin and Skin Structure Infection STudies), of iclaprim for the treatment of complicated skin and skin structure infections (cSSSI). This randomized, blinded, comparator controlled trial enrolled 494 subjects internationally. The trial was designed to compare intravenous iclaprim to linezolid (standard of care). The primary efficacy endpoint, statistical non-inferiority in the clinical cure rate at the Test-Of-Cure (TOC) visit, was achieved. The overall clinical cure rates were 84.9% and 87.2% for iclaprim and linezolid, respectively. The microbiological eradication rates for methicillin-susceptible S. aureus (MSSA) bacteremia were 83.5% and 84.7% for iclaprim and linezolid respectively and for methicillin-resistant strains (MRSA) 77.0% and 80.0%, respectively. The incidence of drug-related adverse events was higher in the linezolid arm compared to the iclaprim arm (34.6% versus 27.9%, respectively). Based on positive phase III results, Arpida plans to file a NDA with the FDA later in 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.
February 26, 2007
Basilea issued positive results from a phase III trial of alitretinoin for the treatment of hand dermatitis. This randomized, double-blind trial enrolled 1,032 subjects whose dermatitis was unresponsive to potent topical steroids. Subjects received a once daily dose of alitretinoin at 10 mg or 30 mg or placebo for a 24 week treatment duration. The primary endpoint was the proportion of subjects with clear or almost clear hands as defined by the Physicians Global Assessment. Treatment was well tolerated with all adverse events dose dependent and reversible. Alitretinoin was statistically superior to placebo at both the high and low dose. In the 30 mg group 48% of subjects (p less than 0.001) and in the 10 mg group 28% of the subjects (p=0.004) reached the primary endpoint compared to a 17% response rate in the placebo group. These results are going to be used as part of a NDA filing later in 2007.
January 29, 2007
Barrier reported positive results from a phase IIa trial of Hivenyl for the treatment of atopic dermatitis. This multi-center, double-blind, placebo-controlled trial enrolled 44 subjects in Belgium and the Czech Republic. After undergoing a one-week lead-in period, subjects were randomized to receive oral Hivenyl 60 mg twice daily or placebo for one week. All subjects were also treated with a topical corticosteroid and an emollient daily throughout the study. Treatment was well tolerated with no signs of sedation. Of the 23 subjects in the Hivenyl treatment group, 9 reported either a marked improvement or an almost complete to complete improvement of their itch symptoms versus none of the 21 subjects in the placebo group (p < 0.01). Additionally, in these nine subjects the overall clinical severity score, as measured by the Eczema Area and Severity Index (EASI), showed a reduction of the atopic dermatitis lesions. Based on these results, Barrier plans to move forward with the development of Hivenyl.
January 15, 2007
Basilea reported positive results from a phase III trial, dubbed STRAUSS II, of ceftobiprole for the treatment of complicated skin and skin structure infections. This trial enrolled 828 subjects who were randomized 2:1 to receive ceftobiprole or the combination of ceftazidime plus vancomycin. Treatment was well tolerated, with adverse events comparable between the two groups. The primary endpoint, statistical non-inferiority between the two treatment groups, was achieved with 91% of the subjects cured with ceftobiprole cured versus 90% cured with the combination therapy. Of the subjects with diabetic foot infection, the clinical cure rate for ceftobiprole was 86% versus 82% for the comparator. Over 20% of the subjects had a methicillin-resistant Staphylococcus aureus (MRSA) infection. The clinical cure rate for ceftobiprole in MRSA subjects was 91% compared to 86% for the combination group. One third of the population had an infection involving a gram negative pathogen. The cure rate between the two treatment groups was the same at 84%. Based on these results, Basilea plans the first regulatory filing for ceftobiprole to take place 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.
Dynavax announced positive results from a phase III trial of Heplisav for the treatment of Hepatitis B. This trial enrolled 400 seronegative subjects who received three doses of the Heplisav vaccine or three doses of Engerix-B, an approved Hepatitis B vaccine. The primary endpoint of the trial was seroprotection four weeks after the third immunization. Results revealed that, after three doses, Heplisav provided seroprotection to 100% of subjects while Engerix-B provided seroprotection to 73.1% (p < 0.0001). The greatest deviation in seroprotection was observed in the subjects aged 56 to 70 years where Heplisav provided 100% seroprotection and Engerix-B provided 56.1% seroprotection. Dynavax plans to initiate phase III trials to investigate a two dose regimen of Heplisav versus Engerix-B by late 2006 to early 2007.
October 9, 2006
Basilea and Johnson & Johnson reported positive results from a phase III trial of ceftobiprole for the treatment of complicated skin and skin structure infections (cSSSI) due to Gram-positive bacteria. The trial was designed to compare the clinical cure rates of ceftobiprole versus vancomycin, a commonly used antibiotic. This multi-center, randomized, double-blind trial enrolled 784 subjects with cSSSI caused by gram positive bacteria. Subjects received ceftobiprole (500 mg IV q 12hr) or vancomycin (1gm q IV 12hr) and were observed 7-14 days after treatment for clinical cure results. Safety and tolerability data revealed that treatment was well tolerated. The most commonly reported adverse events included rashes, nausea and taste disturbances. Efficacy data revealed that cure rates in the ceftobiprole-treated and vancomycin-treated groups were 93.3% and 93.5% respectively. Based on this data the companies plan to move forward in the development of ceftobiprole.
October 2, 2006
Nucryst announced mixed preliminary results from a phase II study of NPI 32101, a topical cream, for the treatment of atopic dermatitis in children and adolescents. This trial enrolled 409 subjects, aged 2 to 17, at 29 sites in the US and Canada. Subjects were randomized to receive 2% NPI 32101 cream, 1% NPI 32101 cream or placebo cream twice daily for 12 weeks. Treatment was well tolerated for both groups, with incidence of reported adverse effects minimal. The trial failed to meet statistical significance in total clearance or almost total clearance between the treatment groups. After 12 weeks of treatment 35.8% of subjects receiving 2% NPI 32101 cream achieved this, versus 35.1% of subjects receiving 1% NPI 32101 cream and 34.6% of subjects receiving placebo cream. Nucryst plans to further analyze this data in order to determine a future course of action for NPI 32101.
September 5, 2006
Connetics issued positive results from a second phase III trial of Extina foam for the treatment of seborrheic dermatitis. This double-blinded, active- and placebo-controlled trial enrolled 1,162 patients at 24 centers in the United States. The trial met the primary endpoint of demonstrating that Extina is superior to placebo foam. This was measured using the Investigator's Static Global Assessment (ISGA), which for this trial was an evaluation of the severity of seborrheic dermatitis determined by the clinically relevant signs of the disease. Efficacy results showed a statistically significant response difference with a 56% response rate for Extina and a 42% response rate for placebo foam (p=0.0001). Based on these results Connetics planned to resubmit a NDA to the FDA by the end of 2006.
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.
July 31, 2006
Foamix reported positive results of a phase I/II trial of their betamethasone valerate 0.12% topical foam, under investigation for the treatment of psoriasis. This randomized, investigator-blinded, controlled study enrolled 30 subjects with bilateral plaque psoriasis. Each patient applied the betamethasone foam to an affected area on one side or their body, and a control cream preparation to a similar area on the other, twice daily for 6 weeks. Trial data yielded a significant improvement in efficacy parameters for more than 84% of subjects after 3 weeks of treatment. Further, subjects reported higher usability for the foam preparation, noting faster absorption and reduced residue after application, compared to the control cream.
Intercytex announced positive results of a phase I trial of ICX-RHY, their investigational cell therapy product for facial rejuvenation. Trial data yielded a positive safety profile, with no serious adverse events reported and an overall tolerability profile including only transient adverse events. This placebo-controlled study enrolled 10 healthy volunteers at the Cranley Clinic in London, under the direction of Dr. Nick Lowe. Subjects received three injections of the drug or placebo into the skin of the upper arm. Based on these results, the company announced plans to initiate a phase II trial of the drug, for the treatment of facial wrinkles, in the second half of 2006.
June 19, 2006
Anacor Pharmaceuticals has issued positive results of a phase IIa trial of AN0128, for the treatment of atopic dermatitis. Results from the study yielded evidence of efficacy, with 47% of subjects achieving an improvements of at least two severity grades on the Investigator Static Global Assessment scale, and achieved ratings of "clear" or "almost clear" (the lowest two severity scores), compared to 29% of subjects receiving vehicle cream. The drug was well tolerated, with no serious adverse events reported; the most common overall adverse events were application site reactions. This multi-center, randomized, placebo-controlled study enrolled 103 subjects with mild to moderate disease across 8 sites, who received either twice daily topical administration of a 1% AN0128 cream or vehicle for 4 weeks. Based on these results, the company announced plans to initiate a phase IIb trial of the drug in late 2006.
March 13, 2006
Corgentech reported positive results of a phase I/II trial of Avrina (NF-kappaB decoy), for the treatment of atopic dermatitis, at the American Academy of Dermatology Meeting in San Francisco. A dose of 0.25% of the drug was shown to significantly reduce total symptom score (p=0.035) and excoriation score (p=0.007), and trended towards efficacy in the combined eczema score, the trial's primary efficacy endpoint (p=0.059). Holdover efficacy was noted up to 2 weeks after treatment discontinuation. Primary safety and tolerability measures were also positive. This randomized, double-blind, placebo-controlled, multi-center study enrolled 75 patients with mild-to-moderate disease in the US, who received one of three doses of the drug (0.25%, 0.5% and 1.0%) or control twice daily for 21 days, with observational follow-up 28 days after treatments.
February 27, 2006
SkinMedica has announced positive results of a pair of phase III trials of Desonate HydroGel 0.05% (topical desonide), for the treatment of atopic dermatitis. Trial data yielded significant evidence of efficacy compared to placebo in both primary measures, the Investigator Global Severity Assessment (44% vs. 14% for placebo; p<0.001) and a composite treatment success endpoint, which included measurement of signs and symptoms of atopic dermatitis, (erythema, induration/papulation, and scaling; 28% vs. 6%; p<0.001). No serious adverse events were reported. These multi-center, randomized, double-blind, placebo-controlled studies enrolled a combined 582 pediatric patients (ages 3 months to 18 years), who received topical administration of the drug or placebo (vehicle gel) twice daily for 4 weeks.
February 13, 2006
Corgentech announced preliminary results of a pair of phase I/II trials of Avrina (NF-kappaB decoy) for the treatment of atopic dermatitis. Both trials were randomized, double-blind, placebo-controlled multi-center studies: the first enrolled 75 subjects in the US, who received 1 of 3 doses of the drug (0.25%, 0.5% or 1.0%) twice daily for 21 days with a 28 day observational follow-up; the second enrolled 120 subjects in Australia and Switzerland, who received the drug (1.0%) or placebo once or twice daily for 28 days with a 14 day follow-up. Data from both studies showed positive preliminary efficacy, with the lowest doses studied in each trial seen as most efficacious; the 0.25% dose used in the US trial approached statistically significant benefit (p=0.059). Further, primary safety and tolerability signals were positive. Full results from the trial were expected in March 2006.
August 8, 2005
CollaGenex issued positive results of a phase II trial of COL-3, for the treatment of rosacea, at the summer meeting of the North Carolina Dermatology Association. The drug met its primary efficacy endpoint, reducing mean lesion count at day 42 by 12.8 per patient, compared to a mean increase of 2.3 lesions per patient receiving placebo (p=0.0213). Furthermore onset of action was observed to be rapid, with 80% of the total endpoint reduction observed by day 14. 75% of patients receiving COL-3 achieved complete or near complete disappearance of symptoms, as measure by Investigators Global Assessment. Finally, incidence of erythema was slightly improved in the COL-3 group (2.5 point reduction in severity) compared to placebo (1.7 point reduction). This double-blinded, placebo- controlled proof-of-principle study enrolled 14 patients, who received 10 mg of the drug (n=8) or placebo (n=6) once daily for 42 days.
Cytochroma has issued positive results of a phase Ib trial of CTA018, their vitamin D analog and CYP24 inhibitor for the treatment of psoriasis. Trial data met their primary safety endpoint, with no serious adverse events reported and positive local and systemic adverse event profiles. Pharmacokinetic data did not indicate systemic exposure 48 hours post treatment in the highest dosing group. This multicenter, 4-arm, randomized, open-label, parallel- group comparison study enrolled 28 patients with plaque psoriasis; subjects received one of three dose concentrations of CTA018 (1, 3, or 10 mcg/g) or vehicle cream, applied to 5% of the body surface daily for 13 days, with a observational follow-up 7 days after treatment. Based on these results, the company announced plans to initiate a phase II trial of the drug in Q4 2005.
Isolagen announced positive results of a phase III trial of their autologous fibroblast transplant therapy, dubbed the Isolagen Process, for the treatment of dermal contour deformities. Results from the parallel-arm study met three of four primary endpoints, producing significant improvements in appearance of contour deformities on both patient and physician visual assessment scales in one arm, but only statistical improvement in patient assessment in the second arm. Significant efficacy variance was noted between investigative sites (range of improvement: 7.6%-73.3%), based primarily on differences in injection technique. This randomized, double blind, placebo-controlled parallel arm study enrolled two study cohorts of 100 patients each across 5 US sites. Based on these results, Isolagen announced that they planned to initiate an additional 100 patient study of the drug with expended training regarding injection technique. This additional trial delays the projected BLA filing date until 2006.
Isotechnika reported positive interim results of their phase III SPIRIT trial of ISA247 for the treatment of psoriasis. Blinded, combined data from all treatment groups from the first 12 weeks of the trial (n=369 patients) yielded a mean reduction in Psoriasis Area and Severity Index (PASI) score of 38%, indicating potential efficacy. The data also indicated a positive safety profile, with the highest variance in serum creatinine levels in any treatment group being 5.6%, a value considered within the normal physiogical range. Less than 2% of subjects in any dosing group withdrew from the study after 12 weeks due to changes in kidney function. This randomized, double-blind study enrolled 453 patients with severe plaque psoriasis across 32 sites in Canada. Subjects received one of 3 doses of ISA247 (0.2 mg/kg, 0.3 mg/kg and 0.4 mg/kg) or placebo twice daily, with subjects receiving placebo switching to the middle dosing regimen after the first 12 weeks of the 24 week study. Full 24 week data was expected during the first half of 2006.
July 25, 2005
Foamix has reported positive results of a phase II/III study of PerFoam (permethrin 1%), their investigational topical foam for the treatment of head lice. Result from the study indicated that the drug killed head lice in 54 of 56 subjects (96.4%) and completely removed lice eggs in 60% of subjects; these results suggest potential of PerFoam in overcoming resistance to shampoo or cream/lotion rinse formulations of permethrin. Safety and tolerability data were positive and yielded possible evidence of superiority to currently approved formulations of permethrin, with no incidence of skin or eye irritation. This open-label study enrolled 56 pediatric patients with head lice at the Laniado Medical Center in Netanya, Israel, under the direction of Dr Avner Shemer. Subjects received initial, 10- minute application of PerFoam at baseline and again at day 10.
July 18, 2005
Critical Therapeutics has issued negative results of a phase II trial of Zyflo (zileuton) for the treatment of inflammatory facial acne. Zyflo is currently approved as a treatment for asthma. Results from the study indicated that the drug failed to meet its primary efficacy endpoint: subjects receiving Zyflo experienced a mean reduction in inflammatory lesion count of 11.5 (33.5%), compared to a reduction of 9.5 lesions (26.9%) for placebo, but the difference between these values was not significant (p=0.384). Mean total lesion count, a secondary efficacy measure, showed a positive trend, but also failed to achieve significance (25.3 fewer lesions for Zyflo vs. 16.4 fewer for placebo, p=0.085). A subset of patients with more severe acne yielded some positive results: absolute mean inflammatory lesion count showed a non- significant positive trend compared to placebo (16.2 vs. 11.7; p=0.063), mean inflammatory lesion count decreased significantly (41.6% vs. 26.2%; p=0.025), and trends towards rapid onset of activity were noted at weeks 4 (p=0.078) and 8 (p=0.057). This randomized, double-blind, placebo-controlled study enrolled 101 patients with moderate to severe inflammatory facial acne across 12 US sites. Subjects were randomized to receive zileuton 600 mg (n=52) or placebo (n=49) four times daily for 12 weeks. The company indicated that they were continuing to interpret data from the study, and expected additional guidance in August 2005.
Novogen, through their subsidiary Glycotex, has reported positive results of a phase II study of their investigational would healing compound glucoprime, for the treatment of venous stasis ulcers. Trial data yielded evidence of efficacy, with mean healing rates of 59% for the low dose glucoprime group and 55% for the high dose group, compared to 10% for placebo. This improvement was noted despite the fact that ulcers in the glucoprime group were substantially larger at baseline. Furthermore, ulcers treated with the drug healed 2 mm/day faster than those treated with placebo. This double-blind, placebo-controlled study enrolled 60 patients with chronic deep venous stasis ulcers of the legs across 2 sites in Australia. Subjects received treatment with either low dose (0.1%) or high dose (1.0%) glucoprime gel or placebo thrice weekly for 12 weeks. The company announced plans to initiate additional trials of the drug, in which patients were to be stratified based on wound severity prior to randomization, based on these results.
May 2, 2005
Isotechnika issued positive preliminary data from a phase III study of their investigational immunosuppressive ISA247 for the treatment of psoriasis. Trial data from the first 200 subjects indicated efficacy in the primary endpoint, producing a reduction in Psoriasis Area and Severity Index (PASI) symptom severity score at 12 weeks, and the degree of score reduction was comparable to those observed in previous studies. Further, preliminary efficacy was noted as early as 4 weeks after beginning treatment. This randomized, double-blind trial enrolled 453 patients with stable moderate to severe plaque psoriasis across 32 sites in Canada. Subjects received one of three oral doses of the drug (0.2 mg/kg, 0.3 mg/kg and 0.4 mg/kg) or placebo twice daily for 12 weeks, followed by an open-label extension through 24 weeks which re-randomized the placebo and low-dose groups to receive therapeutic doses of the drug. The company announced plans to extend the trial through 36 weeks with the 0.3 mg/kg dose to gather long-term safety data.
April 25, 2005
CollaGenex announced positive results of a phase II trial of COL-3, for the treatment of rosacea. At the end of the observation period (42 days), patients receiving COL-3 yielded a significant 69% reduction in lesion count, vs. 12% for placebo (p < 0.01). Furthermore, improvement was also seen in lesion count during interim observations, overall clinical severity score and incidence of erythema. This double-blind, placebo-controlled proof-of- principle study enrolled 13 rosacea patients across 3 US sites, who received COL-3 or placebo for 28 days. The company announced plans to initiate a second proof-of-principle study, in patients with acne, in the near future.
February 28, 2005
Isolagen announced 12 month follow-up data from a phase III trial of their Isolagen Process, which utilizes autologous fibroblasts to treat facial contour deformities. Study data yielded significant evidence of efficacy, with 57.0%, 79.6%, 77.1%, and 82.2% of patients responding (response was classified as a 2 point improvement on a 7 point standardized photoguide scale) at 1, 2, 4 and 6 months respectively, vs. 38.2% at 6 months for placebo (p<0.0001). Follow-up analysis at 12 months yielded an 82.4% response rate. This double-blind, placebo controlled trial enrolled 151 patients with eight types of facial defects, including acne scarring and rhytids, across 10 US sites. These results were in line with those observed in previously completed European and Australian phase III studies, and supports ongoing US phase III studies being conducted under an SPA with the FDA, with an expected BLA filing date during the second half of 2005.
QLT announced positive results of both a phase III efficacy trial and a long term safety study of their investigational acne medication Aczone (dapsone topical gel) at the Annual Meeting of the American Academy of Dermatology in New Orleans. Results from a phase III safety and efficacy study indicated that the drug produced significant reductions in the incidence of both inflammatory and non-inflammatory lesions and in total lesion count, compared to vehicle gel. Secondary efficacy assessment, using a five point static Physicians Global Assessment Scale, also yielded positive results. Results from a long-term safety study indicated that long-term Aczone treatment was well tolerated, with no increases in adverse events or laboratory abnormalities over time. Plasma drug levels remained consistently low plasma. The multicenter, double-blind, phase III study randomized 496 patients to receive either Aczone (n=330) or vehicle gel (n=166) twice daily for 12 weeks. The multicenter, open-label, non-comparative safety study enrolled 506 patients to receive twice daily topical Aczone application for 12-months; 340 completed the full course of therapy.
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.
Isotechnika reported positive results of a dose ranging safety study of their immunosuppressive drug candidate ISA247, under investigation for the treatment of psoriasis. Assembled data indicated that the drug met all safety endpoints, with no clinically significant impact on renal function (as measured by serum creatinine or 24-hour creatinine clearance) and no incidence of serious adverse events associated with clinically relevant doses of the drug. This multiple ascending dose trial enrolled a total of 43 healthy subjects, who received a fixed oral dose twice daily for 10 days, followed by one of three dose levels twice daily for an additional 10 days. The company announced that these results would pave the way for the initiation of a phase III trial of the drug before the end of 2004.
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 11, 2004
Peninsula Pharmaceuticals and Takeda Chemical Industries issued positive results of a phase I trial of PPI-0903, its investigational cephalosporin antibiotic for Gram-positive soft complicated skin and skin-structure infections, and hospital- and community-acquired pneumonias. Preliminary data analysis indicates that the drug was generally safe and well tolerated in both single and multiple dose regimens. Adverse events were transient and mild, no serious adverse events were observed, and no subjects withdrew during the trial. This open-label, sequential dosing regimen study enrolled a total of 14 healthy volunteers, who received escalating single intravenous doses of PPI-0903, followed by an escalating multi-dose regimen of intravenous doses for up to 14 days.
Valeant Pharmaceuticals announced positive end-of treatment data from their phase II study of viramidine for the treatment of Hepatitis C (HCV). These preliminary results indicated that treatment with viramidine demonstrated non-inferior efficacy to ribavirin, an approved HCV therapy at all trial doses, as measured by the percentage of patients with undetectable HCV RNA levels. Furthermore, viramidine produced significantly fewer instances of anemia at all doses (4% vs. 27%, p<0.001), compared with ribavirin; this included no subjects at the lowest dose and only 2% of subjects at the middle dose. The open-label, randomized, active-control, multi-center study enrolled a total of 180 treatment-naïve HCV subjects, who received standard therapy with peginterferon alfa-2a, plus one of three oral regimens of viramidine (400 mg, 600 mg or 800 mg twice daily), or ribavirin (1000/1200 mg daily). Analysis of the data from this trial, as well as two phase III clinical trials of the drug, are ongoing.
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.
August 16, 2004
Astralis reported positive results from a phase I trial investigating Psoraxine, an injectable treatment for moderate psoriasis. Results showed that treatment with Psoraxine was generally well tolerated with a similar safety profile to that of placebo. In addition, more subjects in the Psoraxine groups exhibited improvements in the total and partial PASI scores at Day 14 than in the placebo group. The score for itching also showed an improvement in the Psoraxine groups as compared to the placebo group. No subjects evaluated developed skin anergy, a state of immune unresponsiveness, to standard recall antigens. The randomized, double-blind, placebo-controlled, parallel group, dose-ranging study enrolled 21 subjects with moderate and clinically stable plaque psoriasis. Subjects were given a single intramuscular injection of Psoraxine (50 mg, 150 mg, or 300 mg).
August 9, 2004
Astralis has announced the results of its phase I study of Psoraxine, a protein immunotherapy product being investigated for the treatment of psoriasis. Trial data have indicated that the drug is safe and well tolerated, with similar adverse event profiles observed among all three trial doses of the drug and placebo. In addition, despite the fact that doses used in the trial were considered sub-optimal for producing therapeutic response, evidence of efficacy was observed, with a greater number of patients showing improvement in each of the trial groups than the placebo group. The double-blind, placebo-controlled, parallel group, dose-ranging study randomized a total of 21 subjects, who received one of three doses of Psoraxine or placebo via single intramuscular injection, followed by a 14 day observation period.
August 2, 2004
Abbott has announced positive results of a phase II study in their supplemental development of Humira (adalimumab) for the treatment of chronic plaque psoriasis. Study data indicated that the drug is efficacious in both mitigating disease symptoms and improving quality of life of psoriasis sufferers. The double-blind study enrolled a total of 148 subjects into weekly or bi-weekly regimens of Humira or placebo. Weekly Humira treatments resulted in 72% of subjects achieving a 75% improvement in disease state, and 62% achieving 90% improvement, and all Humira regimens produced significant improvements over placebo on the DLQI index, a standardized measurement of the impact of psoriasis on quality of life. No new safety concerns were raised, and the drug was generally well tolerated. Humira is currently approved for the treatment of rheumatoid arthritis.
Isolagen has reported 6-month interim results of their first phase III study of their Isolagen Process, the use of autologous fibroblast cells to fill facial contour deformities. Data from the ongoing study indicate that the treatment appears to be efficacious in alleviating facial contour deformities, with 77% of subjects achieving clinical response at 4 months and 82% achieving response at 6 months. The study has evaluated 146 subjects, 90.5% of whom were female and 91.8% of whom were Caucasian. Isolagen announced that the study would continue for another 6 months, and that they expected regulatory filing by Q1, 2005.
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.
Isolagen reported initial results from a phase III trial investigating the Isolagen Process, an autologous cellular therapy for the aid in hard and soft tissue regeneration. Results showed a statistical significance of 77% efficacy in the Isolagen treated group compared to a 36% response with the placebo-controlled group. Data revealed that subjects who received the Isolagen Process showed a four-fold improvement in baseline values, as compared with placebo. The 4-month, double-blinded, placebo-controlled study enrolled 158 subjects and was conducted at ten sites. Subjects received therapeutic or placebo injections and were blindly assessed by comparison to either a seven-point photo scale or a subjective visual analogous scale. Subjects had to improve two or more points to qualify as a responder.
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.
May 19, 2003
Vicuron reported positive results from a phase II trial investigating dalbavancin, a glycopeptide antibiotic for the treatment of skin and soft tissue infections (SSTIs). Results showed higher clinical and microbiological response rates compared to a variety of standard care regimens. Data demonstrated higher clinical (94.1%) and microbiological (72.7%) response rates for deep SSTIs with two doses versus a single dose of dalbavancin (61.5% clinical; 27.3% microbiological) or control (76.2% clinical; 64.3% microbiological). The control arm consisted of investigator-specified standard of care such as treatment with one of the antibiotics, clindamycin, ceftriaxone, vancomycin or cefazolin. The randomized, controlled study enrolled 62 subjects with complicated SSTIs. Dalbavancin was well tolerated and adverse events were infrequent. Results were presented at the European Congress of Clinical Microbiology and Infectious Diseases.
April 1, 2002
Atrix Laboratories has reported positive results from the first phase III trial with Atrisone, for the treatment of acne. Atrisone (dapsone 5%) is a twice-daily drug administered via Atrix's SMP topical drug delivery technology. Based on the 500 subject, double-blind, vehicle-controlled study, Atrisone was found to be clinically superior to vehicle (SMP alone) on all four primary and both secondary endpoints. Primary endpoints included reduction in inflammatory and non-inflammatory lesion counts, reduction in overall lesion count and improvement in overall appearance. The secondary endpoints of the trial were lesion count change from baseline and percent change from baseline. Atrix plans to move forward with a second phase III trial with Atrisone.
March 11, 2002
Positive results were reported from a phase II trial of topical alicaforsen (ISIS 2302) in subjects with mild to moderate plaque psoriasis. The double-masked trial, which included 31 subjects, compared 4% topical alicaforsen cream to placebo. Fifteen subjects in the trial applied treatment once per day, while 16 applied twice per day. Results showed that treatment with alicaforsen resulted in statistically significant improvement in Investigators Global Response Score (IGRS) at week four and a positive trend toward improvement at week eight. Furthermore, alicaforsen produced a 31% improvement from baseline in terms of plaque induration at both four and eight weeks. Alicaforsen is being developed by Isis Pharmaceuticals.
March 5, 2002
Data from a pooled analysis of two phase III trials indicates that Xanelim (efalizumab) produces an early clinical improvement in subjects with moderate-to-severe psoriasis. In the two trials, 1,095 subjects received weekly subcutaneous doses of 1 mg/kg Xanelim, 2 mg/kg Xanelim or placebo. At 12 weeks, mean PASI score improvements were 14% for the 1 mg/kg Xanelim group and 13% for the 2 mg/kg group, compared to 8% for placebo-treated subjects. Furthermore, after 12 weeks, 29% of subjects treated with 1 mg/kg Xanelim and 28% of those treated with 2 mg/kg achieved PASI score improvement of 75% or greater, versus 3.4% of those receiving placebo. Xanelim is being developed by Genentech and Xoma.
Phase III trial results suggest that Novartis' Elidel (pimecrolimus) cream 1% is more effective than a conventional treatment in reducing the incidence of disease flares. The 12-month, multicenter, double-blind study included 713 pediatric eczema subjects ages two to 17 years. The trial compared a long-term Elidel treatment regimen with a current conventional therapy regimen. Subjects applied either treatment at the earliest signs or symptoms of the disease. Both groups also used topical corticosteroids to treat any severe flares. At both six and 12 months, results showed that Elidel significantly reduced flare incidence compared to the conventional therapy. Additionally, 57% of subjects treated with Elidel had no flares that required corticosteroid treatment, compared to 32% in the control group.
January 7, 2002
Positive phase I results were reported from testing of 5G1.1 in 13 subjects with dermatomyositis. The drug, a humanized monoclonal antibody C5 complement inhibitor in an intravenous injection formulation, appeared to be well tolerated and to improve skin rash. Treatment was given once a week for five weeks, then every two weeks for up to two months. Though safety was the primary study aim, measurements of skin rash and muscle strength were also recorded, showing consistent trends in improvement with drug administration. Few adverse events were observed, and those seen were comparable for treatment and placebo groups. 5G1.1 is being developed by Alexion Pharmaceuticals.
December 10, 2001
Preliminary phase II trial results indicate that Micrologix Biotech's MBI 594AN produced a 32% reduction in total acne lesion counts (inflammatory plus non-inflammatory lesions) compared to a 14% reduction for placebo. The randomized, double-blind trial enrolled 75 acne subjects who received twice-daily dosing with either one of two formulations of MBI 594AN (2.5% and 5%) or the product's alcohol-based vehicle alone. Subjects treated with MBI 594AN showed a 39% reduction in inflammatory acne lesion counts compared with 21% for the placebo group. In terms of non-inflammatory acne, MBI 594AN treated subjects experienced a 25% improvement in lesion reduction, compared to 10% for placebo treated subjects.