Office (925) 480-7497
Mobile (925) 413-7297
Email: aretzios@ADRclinresearch.com

Title Banner

Pharmaceutical and Biotech News

A

May 27, 2011

FDA approves Optimer's fidaxomicin (Dificid®) for the treatment of  Clostridium difficile-Associated Diarrhea (CDAD)

Fidaxomicin (Dificid®) belongs to a new class of narrow-spectrum macrocyclic antibiotics (compounds that include a ring of at least 7 atoms).  It is poorly absorbed, resulting in topical, non-systemic exposure.  It affects mainly the pathogenic Clostridium difficile without disrupting the rest of the intenstinal flora.  It works by inhibiting the RNA polymerase of the target bacterium.

Optimer performed two pivotal studies with fidaxomicin in a total of 584 patients with CDAD.  Both were randomized (1:1), double-blind, multicenter, actively-controlled, noninferiority trials. The control agent was vancomycin and the non-inferiority delta was set at 10%.  Both trials compared 10 days of fidaxomicin at 200 mg orally bid to 10 days of vancomycin 125 mg orally qid in subjects with CDAD. Randomization was assisted by stratification according to prior CDAD episode.  Two strata were defined: 1) no prior episode in the last 3 months or 2) a single prior episode in the last 3 months. In both studies, the cure rate with fidaxomicin was similar to that of vancomycin (88% vs. 86%; 88% vs. 87%).  However, fidaxomicin was superior to vancomycin in global cure which is defined as cure with no recurrence at follow-up (70% vs. 57% ; 72 vs. 57%).

May 13, 2011

FDA approves Merck's boceprevir (Victrelis®) for the Treatment of Hepatitis C in Patients with Compensated Liver Disease

In fact, the FDA-approved indication is quite narrow,  Boceprevir (Victrelis®), a protease inhibitor, has been approved for the treatment of chronic hepatitis C (CHC) genotype 1 infection (which is usually difficult to treat), in combination with peginterferon alfa and ribavirin, in adult patients (≥18 years of age) with compensated liver disease, including cirrhosis, who are previously untreated or who have failed previous interferon and ribavirin therapy.

The safety and effectiveness of Victrelis was evaluated in two phase 3 clinical trials that enrolled approximately 1,500 adult patients. In these multicenter, double-blind and placebo controled studies, the patients were randomized into three groups.  One of the groups received placebo plus peginterferon-ribavarin for 44 weeks, the 2nd received boceprevir plus peginterferon-ribavarin for 44 weeks and the third received boceprevir plus peginterferion-ribavarin for 24 weeks, with the patients positive for HepC mRNA receiving placebo plus peginterferon-ribavarin for an additional 20 weeks.

Both trials showed a significantly higher sustained virologic response (No dectetable virus, with a possibility of relapse at below 2%) in the treatment arm (66-67%) when compared to placebo (21-40%). Common adverse events were anemia and dysgeusia. 

 

April 15, 2010

Idenix Pharmaceuticals Reports Positive Results With IDX184 From Interim Analysis of Phase IIa Hepatitis C Study: IDX184 is a nucleoside polymerase inhibitor developed by Idenix .  The ongoing phase IIa clinical trial is a double-blind, sequential dose-escalation study to evaluate the safety and efficacy of IDX184 in combination with pegylated interferon(pegIFN) and ribavirin in HCV genotype 1-infected patients versus placebo (plus pegIFN/ribavirin). Treatment consists of a daily dose of IDX184 or placebo, plus pegIFN/ribovarin for 14 days and then PegIFN/ribavarin for an additional 14 days.  In the data presented today, IDX184 demonstrated dose-dependent antiviral activity.  Half of the subjects receiving a total daily dose of 100 mg IDX184 achieved undetectable virus levels (< 15 IU/mL) by Day 14. Liver injury parameters (ALT and AST) improved (normalized) with all doses of IDX184. The adverse experience (AE) profile of the three-drug combination was consistent with the known AE profile of PegIFN/ribavarin alone. The most common adverse events reported were fatigue, myalgia, headache and nausea.

Comment: Treatment of HCV is an extremely active area of drug development with approximately 140 drugs in development currently.  Major pharmaceutical and smaller biotech companies are pursuing various compounds that include, among others, protease polymerase inhibitors and nonstructural protein 5A (NS5A) inhibitors and therapeutic vaccines.

April 14, 2010

InterMune Reports Top-Line Results From Phase 2b Study of Danoprevir in Patients with Chronic Hepatitis C: Danoprevir (also known as RG7227 or ITMN-191) is macrocyclic inhibitor of HCV NS3/4A protease activity. The Phase 2b clinical trial reported was a randomized, partially-blind study evaluating danoprevir, administered for 12 weeks in combination with Pegasys® (pegylated interferon alfa-2a) and Copegus® (ribavirin), compared with placebo plus Pegasys® and Copegus® for the same period of time. Three doses/dose regimens of danoprevir (300 mg -q8hr, 600 mg - q12hr, 900mg - q12hr) were tested.  At 12-weeks, patients with virologic response were 88%, 89% and 92% of participating subjects, respectively, vs. 43% for placebo + ribavirin + pegylated interferon.  Safety was comparable in all groups.  Intermune is developing danoprevir in association with Roche.  The companies announced that future studies of danoprevir will examine its efficacy when administered in lower doses in combination with ritonavir (Norvir®), a currently marketed protease inhibitor.

April 12, 2010

Positive Results of the 2nd Phase 3 Study of Fidaxomicin for the Treatment of Clostridium difficile Infection (CDI): Fidaxomicin is represents a new class of antibiotics called macrocycles, which inhibit  bacterial RNA polymerases. It targets Clostridium difficile narrowly, without disturbing the typical intestinal flora. It is developed by Optimer Pharmaceuticals, Inc.  The final Phase 3 compared fidaxomicin to vancomycin in 535 adult subjects with confirmed C. difficile infection. The study met the primary endpoint of non-inferiority to vancomycin for the 10-day treatment period.  However fidaxomicin showed statistically lower recurrence rates compared to Vancocin (p = 0.002), and significantly higher global cure rates (defined as cure with no recurrence within four weeks of completing therapy) compared to vancomycicin (p < 0.001).

March 30, 2010

PolyMedix Successfully Completes Phase 1B Clinical Study With Novel Antibiotic PMX-30063 (by Businesswire). PMX-30063 a small molecule mimetic of human host-defense proteins.  The company claims that this antibiotic possesses unique advantages such as (a) mechanism of action directed at the biophysical disruption of bacterial cell membranes which may make resistance difficult to evolve (b) Activity against both Gram-positive and Gram- negative bacteria, and (c) activity against 146 different strains of Staphylococcus bacteria, including drug-resistant strains of Staph bacteria (MRSA).  PolyMedix, a Pennsylvania-based company is developing a number of anti-infective compounds.