April 10, 2017
Paratek Pharmaceuticals reported results of a phase III trial comparing omadacycline to moxifloxacin in the treatment of patients with community-acquired bacterial pneumonia (CABP). The OPTIC study was a double-blind, active-controlled, global, multicenter study that enrolled 774 adult subjects with moderate to moderately severe CABP and included approximately 14% PORT Class II, 57% PORT Class III and 28% PORT Class IV. Patients initially received IV administration of either 100mg of omadacycline or 400mg of moxifloxacin. Study investigators were permitted to switch patients to oral dosing of their assigned drug (300mg once daily omadacycline or 400mg once daily moxifloxacin) for a total of seven to 14 days based on assessment of clinical stability. In the study, 774 patients were randomized. Omadacycline met the FDA-specified primary endpoint of statistical non-inferiority (NI) in the intent-to-treat (ITT) population (10% NI margin, 95% confidence interval) compared to moxifloxacin at the early clinical response (ECR) 72-120 hours after initiation of therapy. The ECR rates for the omadacycline and moxifloxacin treatment arms were 81.1 % and 82.7%, respectively. Additionally, the FDA-specified secondary endpoints evaluated omadacycline at the post treatment evaluation (PTE) visit five to 10 days after the completion of therapy in both the ITT population (87.6% for omadacycline vs. 85.1% for moxifloxacin) and in the clinically evaluable (CE) population (92.9% for omadacycline vs. 90.4% for moxifloxacin) as determined by investigators. The secondary endpoints also achieved statistical non-inferiority. This study will be used to support marketing applications to the FDA and the EMA.
January 12, 2015
Cempra issued results of a global, pivotal
phase III trial of solithromycin oral capsules
(Solitaire-Oral) for the treatment of patients
with community acquired bacterial pneumonia
(CABP). This phase III study, Solitaire-Oral,
was a double-blind, active-controlled, global,
multi-center trial that enrolled 860 adult
patients with moderate to moderately severe
CABP (pneumonia of PORT Class II, III and IV
severity classification). Patients were randomized
to receive either oral solithromycin, as an
800mg loading dose followed by 400mg once
daily for a total of five days, or oral moxifloxacin
dosed at 400mg once daily for seven
days. In the intent-to-treat population (ITT, all
randomized patients), solithromycin met the
primary objective of statistical non-inferiority
(10% non-inferiority margin) of the early
clinical response at 72 (-12/+36) hours after
initiation of therapy compared to moxifloxacin.
Solithromycin also met the secondary
objectives of non-inferiority in clinical success
at the short-term follow-up (SFU) visit, five
to 10 days after the end of therapy, both in
the ITT and clinically evaluable populations.
The point estimates for the primary endpoint
of early clinical response were 78.2% for
solithromycin and 77.9% for moxifloxacin. The
95% confidence interval for the treatment
difference had lower and upper bounds of
-5.5% and 6.1%, respectively. Cempra initiated
the second phase III trial of solithromycin,
Solitaire-IV, in December 2013 and a third trial,
Solitaire-U, began in August 2014 in patients
with uncomplicated gonorrhea and chlamydia
May 6, 2013
Chimerix reported results from a phase II trial of CMX001 for the treatment of life-threatening infection with adenovirus (AdV). This open label, expanded access study enrolled 57 patients infected with AdV. Subjects received oral CMX001 twice weekly. The median duration of CMX001 treatment was 12 doses over seven weeks, with the longest duration of treatment of 43 weeks. Data demonstrated that 34/57 patients (79%) had at least a 90% decrease in the amount of virus in the blood at the end of treatment. Subjects who had a 90% decrease in AdV blood levels had overall better outcomes, with 9% AdV-associated deaths, compared to a 27% mortality rate for patients who had less than a 90% decrease in viral levels. Subjects who began CMX001 therapy as soon as virus was detected in the blood and before symptoms were present, had a lower mortality rate of less than 7%, while patients who were treated after virus was detected in the blood and symptoms had developed had a mortality rate of 37% during the one-month follow-up period. The drug was well tolerated. Based on these results, Chimerix initiated a phase II study of CMX001 as an early treatment for AdV infection in young adults and children who have received a stem cell or bone marrow transplant.
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 29, 2009
Forest Laboratories issued positive results from two phase III trials of ceftaroline for the treatment of community-acquired bacterial pneumonia (CABP). These global, randomized, double-blind, comparative trials, dubbed FOCUS-1 and -2, enrolled 1,241 subjects with moderate to severe CABP requiring treatment with intravenous antimicrobials. The subjects received a 5-7 day treatment course of ceftaroline, 600 milligram twice a day compared with ceftriaxone (standard of care), 1 gram once a day. The primary endpoint was non-inferiority between the two arms in clinical cure rates. In FOCUS I, the clinical cure rate in the ceftaroline-treated arm was 86.6% compared with 77.7% in the ceftriaxone-treated arm. In FOCUS II, the respective rates were 82.1% versus 77.2%. According to the integrated data, in subjects infected with Streptococcus pneumoniae, the most common pathogen in CABP, the clinical cure rates achieved with ceftaroline were 85.5% and 68.6% for ceftriaxone. Adverse events were similar between treatment groups.
October 27, 2008
Novexel released positive results from a phase II trial of NXL103 for the treatment of community acquired pneumonia (CAP). This double-blind, multinational, randomized, comparative study enrolled 300 subjects with mild to moderate CAP. The subjects were randomized to three treatment arms: 500mg of NXL103 twice a day, 600mg NXL103 twice a day or 1,000 mg of amoxicillin three times a day, all for seven days. The primary endpoints were the clinical efficacy at the early follow-up visit (7 to 14 days post-therapy) and safety. Both doses of NXL103 were effective, with clinical response rates similar to those seen in the amoxicillin group. The response rates were 91.4% in the 500mg NXL103 group; 94.7% in the 600mg NXL103 group; and 88.5% in the amoxicillin group. NXL103 was generally well tolerated and no serious adverse events were reported. Full results are expected in 2009
April 14, 2008
Parion issued mixed results from a phase I trial of P-552-02 for the treatment of dry mouth associated with primary Sjogren's syndrome. This twenty-eight day, randomized, double-blind, placebo- controlled, crossover study enrolled thirty subjects who received a six-time daily oral rinse formulation of P-552-02 or placebo. The primary efficacy endpoint, a global improvement in the "feeling of dry mouth" as determined by a single retrospective "recall" report at day twenty eight, was not met. However, an assessment of "global change in dry mouth" as determined by the change in visual analog scale (VAS) measurements twelve hours after dosing at day seven and day twenty eight revealed significant improvement in the global dry mouth scores over placebo. Based on the results Parion plans to proceed with a phase I/IIa study designed to test the efficacy of higher concentrations of P-552-02.
TaiGen released positive results from a phase II trial of nemonoxacin for the treatment of community-acquired pneumonia (CAP). This randomized, double-blind, comparative trial enrolled two hundred and sixty seven subjects. The primary endpoint was the non-inferiority of nemonoxacin in the clinical cure rate of CAP compared with levofloxacin, the current standard of care. Nemonoxacin 750 mg administered orally once daily over a period of seven days achieved non-inferiority in clinical cure rate of CAP compared with levofloxacin 500 mg once daily. Overall, 82.6% of the intent-to-treat population and 90% of the evaluable population were cured with nemonoxacin compared with 80.0% and 91% cure rate in the levofloxacin arm. Treatment was safe and well tolerated, with an adverse event profile similar between the two treatment arms. Based on the positive results, a phase II trial evaluating once-a-day intravenous dosing is scheduled to enter clinical trial the second quarter of 2008.
December 10, 2007
Theravance issued positive results from two phase III trials of telavancin for the treatment of hospital-acquired pneumonia (HAP). These multi-center, multinational, double-blind, randomized studies, dubbed ATTAIN I and II, enrolled 1,503 subjects, 464 of whom were infected with methicillin-resistant Staphylococcus aureus (MRSA). The subjects received either telavancin 10 mg/kg intravenously once daily or vancomycin 1 g intravenously every twelve hours. The primary endpoints were non-inferiority of telavancin versus vancomycin in clinical cure rate at the test-of-cure visit and superiority in clinical cure rate of telavancin versus vancomycin in the pooled subjects with MRSA infections from both trials. Both endpoints were achieved. In the combined clinically evaluable population, the clinical cure rate for telavancin was 82.7%, compared with 80.9% for vancomycin. In the subgroup of subjects with MSRA infections, treatment with telavancin resulted in a clinical cure rate of 82%, compared with 74% for vancomycin. Based on the results Theravance plans to move towards regulatory approval.
November 26, 2007
Advanced Life Sciences reported positive results from a phase III trial of cethromycin for the treatment of community acquired pneumonia. This double-blind, randomized, comparator study, dubbed CL-05, enrolled 584 adult subjects in the US, Canada and South Africa. The subjects received cethromycin 300 mg once-daily or Biaxin 250 mg twice-daily, the current standard of care, for seven days. The primary efficacy endpoint was statistical non-inferiority in the clinical cure rate at the test-of-cure visit between the two treatment arms. This endpoint was achieved, with a clinical cure rate in the cethromycin group of 94.0% compared to Biaxin with a cure rate of 93.8%. In the bacteriologically evaluable population, cethromycin had a clinical cure rate of 95.9% compared to Biaxin with a cure rate of 97.1%. Treatment was well tolerated. Based on the results, Advanced Life Sciences plans to move towards the filing of an NDA with the FDA.
Novartis reported positive results from a phase II trial of Menveo, a vaccine for the prevention of meningitis in infants. This trial enrolled 175 infants who were randomized to receive either two doses of Menveo at both six and twelve months of age, one dose of Menveo at twelve months or a currently approved meningococcal meningitis serogroup C vaccine also at twelve months and then followed by Menveo at eighteen months. Following vaccination, the infants were measured for immune response to antigens via the hSBA, or the human serum bactericidal antibody assay. One month after vaccination, infants receiving Menveo achieved protective antibody levels >1:4 for all four meningococcal serogroups (A, C, W-135 and Y). After two doses of Menveo, the percentage of infants achieving hSBA titer >1:4 was 100% for the serogroups C, W-135 and Y35 and 86% for serogroup A. After a single dose of Menveo at twelve months, the percentages were > 93% for serogroups C and W-135 and > 75% for serogroups A and Y. Of the infants who received the Menveo booster at eighteen months following a single dose at twelve months, 100% achieved hSBA titers > 1:4 for serogroup C, 62% for A, 84% for W-135 and 81% for Y. Treatment was well tolerated in this population. Treatment was well tolerated. Phase III trials are underway and regulatory submissions are expected in 2008.
October 1, 2007
Johnson & Johnson released positive results from a phase III trial of doripenem for the treatment of nosocomial pneumonia. This open-label, randomized, multi-center enrolled 448 subjects who received either a one-hour IV infusion of 500 mg of doripenem every eight hours or a 30-minute IV infusion of 4.5 g piperacillin/tazobactam administered every six hours. Doripenem was shown to be as effective and well tolerated as piperacillin/tazobactam therapy. In clinically evaluable subjects, doripenem demonstrated an 81.3% clinical cure rate compared to a 79.8% rate for the piperacillin/tazobactam group. In addition, a greater proportion of bacteria were resistant to piperacillin/tazobactam compared with doripenem. The minimum inhibitory concentration (MIC) of greater than or equal to 16 mcg/mL) in subjects with Pseudomonas aeruginosa were 27% vs. 4%, respectively and in subjects with Klebsiella pneumoniae were 43% vs. 0%, respectively. A NDA for doripenem in the treatment of nosocomial infections is currently under review by the FDA.
September 24, 2007
Basilea released positive results from a phase III trial of ceftobiprole for the treatment of community-acquired pneumonia (CAP) in subjects requiring hospitalization. The trial was designed to compare the clinical outcomes following the treatment with ceftobiprole versus ceftriaxone with or without linezolid. The primary endpoint of non-inferiority was achieved. The clinical cure rate at the test-of-cure visit was 86% for ceftobiprole and 87% for the comparators. The microbiological eradication rates were 88% and 92% in the ceftobiprole and comparator arm, respectively. In a clinically evaluable group of subjects with moderate to severe pneumonia, the clinical cure rate was 89% and 81% for the ceftobiprole and comparator arms, respectively. A NDA is currently under review for ceftobiprole for the treatment of complicated skin and skin structure infections.
June 25, 2007
Advanced Life Sciences reported positive results from a phase III trial of cethromycin for the treatment of community acquired pneumonia (CAP). This pivotal, randomized, double- blind comparator study, dubbed CL-06, enrolled 522 subjects in South America, Israel and Europe. Subjects were placed in two trial arms to receive 300 mg once-daily cethromycin or 250 mg twice-daily Biaxin (an FDA approved antibiotic), for 7 days. The trial was designed to investigate the safety and efficacy of the drug; the primary endpoint was establishing a non-inferior clinical cure rate at the test-of-cure visit. Cethromycin achieved non-inferiority in this endpoint when compared to Biaxin (cethromycin 91.5%; Biaxin 95.9% [-9.1, +0.3], p=0.0775). Treatment was well tolerated, with adverse events similar between the two arms. Advanced Life Sciences is collecting data from a second phase III trial of cethromycin and plans to report data shortly.
March 28, 2005
Dynavax Technologies has issued positive results of a single-season phase I trial of their investigational ragweed allergy immunotherapeutic AIC. Trial data met their primary safety endpoints, with no serious local or systemic adverse events and a positive tolerability profile. Significance was observed in key secondary immunologic endpoints, with drug administration producing an increase in both anti-ragweed and anti-Amb a 1 antibody immunoglobulin (Ig) G levels vs. both baseline and placebo (p<0.05), with no significant increase in IgE allergic antibody levels. Drug administration also yielded secondary evidence of efficacy, with a statistically significant decrease in late-phase skin test reaction (p=0.008) and a clinically relevant decrease in symptom intensity (p=0.052), vs. placebo. This single-center, double-blinded, placebo-controlled study enrolled 18 ragweed-allergic patients, and was designed to investigate the safety and tolerability of the drug. Subjects were randomized 2:1 to receive escalating doses of AIC (0.3-30 mcg) or histamine placebo via weekly injection for 7 weeks. The company announced that these data would be used to support their ongoing phase II/III trial of the drug.
ID Biomedical announced positive results of several phase I studies of their Pneumococcal Group-Common Vaccine (PGCvax), under development for the prevention of diseases caused by Streptococcus pneumoniae. Combined results indicated that the drug was safe and well tolerated across multiple age groups, including pediatric patients and the elderly. In addition, significant antibody responses were noted in 92% of young adults and 85% of elderly subjects receiving optimal doses of the vaccine, with 9.0 fold mean increase for both groups (p<0.0001). These safety and immunogenicity trials enrolled toddlers, young adults and elderly subjects, who received one or 2 doses of either the drug or placebo. Based on these results, the company announced that it had received clearance from Canadian regulatory authorities to initiate a Phase 1 study of the drug in 75 infants.
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.
September 7, 2004
Oscient published two studies of once-daily Factive, for the treatment of respiratory infections including community-acquired pneumonia and bacterial exacerbations of chronic bronchitis. The studies found that Factive offered a superior option to two other approved antibiotic regimens (gemifloxacin and amoxicillin/clauvulanate): Factive was significantly more efficacious than treatment with gemifloxacin and produced fewer adverse events, and significantly fewer subjects withdrew from Factive treatment than amoxicillin/clauvulanate due to lack of efficacy. Factive also offered a les frequent and/or shorter dosing schedule than either other therapy.
July 5, 2004
Immtech International reported positive preliminary results of their phase II trial investigating DB289, for the treatment of Pneumocystis carinii pneumonia (PCP) in AIDS patients. Data from the first cohort of subjects have indicated that investigational doses of the drug have been safe and efficacious in treating PCP infection. The first cohort in this open label study received a pilot dosing regimen of 50 mg of DB289 twice daily for 21 days. A second study cohort is currently being treated with a 100 mg twice-daily regimen of the drug, and preliminary data from this group show a dose dependent improvement in efficacy and a reduction in time to return to normal lung function over the pilot group. The study is being conducted is being conducted in PCP-treatment-refractory AIDS patients in Peru.
August 12, 2002
Analysis has been completed for the second, previously halted, trial of Cidecin for the treatment of community acquired pneumonia (CAP) in subjects who required hospitalization. Neither the results of the original CAP1 trial nor the 170 evaluable subjects in the CAP2 trial met the statistical endpoint. The trials compared Cidecin to ceftriaxone (the current standard treatment for CAP). In addition, when data from the two CAP study populations were combined, Cidecin achieved a clinical success rate of 80%, while ceftriaxone achieved a clinical success rate of 88%. Cidecin, which is being developed by Cubist Pharmacetuicals, has also completed phase III trials for the treatment of complicated skin and soft tissue infections. Those trials achieved statistical significance.