Replies to post #111876 on Biotech Values

[DewDiligence]

Whatever the scientific merit of including ribavirin in an all-oral HCV cocktail may be, there’s a sound business reason for including it—at least for the time being—insofar as ribavirin allows companies to test 3-drug all-oral cocktails where one of the three drugs is a known quantity.

Compared to a 3-drug cocktail in which all three drugs are unapproved, a cocktail consisting of ribavirin and two unapproved drugs is less likely to induce safety signals that could cause the FDA to impose a clinical hold on the experimental drugs.

[DewDiligence]

…smart to save money recruiting a positive control before you even know if DAAs + rib without interferon is a viable combination

I agree.

[DewDiligence]

ABT Reports Interim Phase-2 HCV Data for ABT-450

[ABT-450 is a protease inhibitor that requires boosting with ritonavir to enable qD dosing. In #msg-56272166 (from Nov 2010), I said: “All told, my assessment of ABT-450 is that it’s a day late and a dollar short; the requirement for ritonavir boosting does not help.” That’s still my view; however, I think ABT is a compelling buy even if the company’s HCV program (which includes several compounds aside from ABT-450—see #msg-47300850 and http://clinicaltrials.gov/ct2/show/NCT01074008 ) is valued at zero.]

http://finance.yahoo.com/news/Abbott-and-Enanta-Present-prnews-564620397.html?x=0

›April 4, 2011, 6:30 am EDT

ABBOTT PARK, Ill., and WATERTOWN, Mass., April 4, 2011 /PRNewswire/ -- Abbott (NYSE:ABT) and Enanta Pharmaceuticals today announced 12-week results from a Phase 2 study of ABT-450/r, an investigational, oral protease inhibitor being developed for the treatment of hepatitis C (HCV) infection. Study results show that 92 percent (22 of 24) of patients taking ABT-450/r once daily, combined with standard of care, achieved complete early virologic response (HCV RNA levels <25 IU/mL) at 12 weeks. Results were presented at the European Association for the Study of Liver Disease (EASL) annual meeting in Berlin.

Key findings:

• At week 12, 92 percent of patients receiving ABT-450/r (ABT-450 with 100 mg of ritonavir to support once-daily dosing) in combination with standard of care (SOC) – pegylated interferon alpha and ribavirin (pegIFN/RBV) – achieved HCV RNA <25 IU/mL

• In a separate analysis of 3-day resistance data, ABT-450/r dosed at 200/100 mg appeared to more consistently suppress the emergence of ABT-450-associated resistant variants than the 50/100 mg and 100/100 mg doses [as one would expect]

• Previously presented 3-day and 4-week results from the study had suggested the ABT-450/r demonstrated significant antiviral activity in treatment-naive adults

• After three days, treatment with ABT-450/r alone resulted in 4-log (10,000-fold) mean reductions of HCV RNA, across the three dose ranges of ABT-450 (50 mg, 100 mg, 200 mg, once-daily dosing)

"A significant number of HCV patients are unable to begin treatment with peginterferon and ribavirin, and for those that do begin treatment, more than 50 percent will not be cured," said Fred Poordad, M.D., chief of hepatology at the Liver Disease and Transplant Center at Cedars-Sinai Medical Center in Los Angeles, and one of the investigators for the study. "These results suggest that ABT-450/r could be an important component in combination therapy approaches to treating HCV."

"Abbott is working to transform treatment options for patients with HCV infection by investigating ways to simplify treatment and increase cure rates," said Scott Brun, M.D., divisional vice president, infectious disease development, Abbott. "We will continue to explore the use of ABT-450/r and our other investigational HCV treatments in a variety of patient populations and combinations, with and without pegylated interferon alpha."

"We continue to be encouraged by the results for ABT-450/r and the potential it holds for treatment-experienced and treatment-naive patients with HCV," said Jay Luly, Ph.D., president and chief executive officer, Enanta Pharmaceuticals.

Study Objectives and Design

The objectives of the 48-week Phase 2 study are to assess the safety, tolerability, pharmacokinetics, and antiviral activity of multiple dose strengths of ABT-450/r in treatment-naive adults infected with HCV genotype 1, which is the most common and difficult to treat form of the infection in the developed world. Trial endpoints include early virologic response and rapid virologic response. Initial antiviral activity was evaluated via a 3-day treatment period during which ABT-450/r was administered alone. Subsequently, ABT-450/r was administered with pegIFN/RBV (SOC) for 12 weeks, followed by treatment with SOC alone for an additional 36 weeks. Participants are then monitored post therapy for 24 weeks for sustained virologic response.

In the trial, the most common adverse events reported in subjects receiving ABT-450/r in combination with pegIFN/RBV were headache, fatigue, insomnia and depression. A similar proportion of subjects reported at least one adverse event in all treatment groups, including placebo.

ABT-450 is being developed with low-dose ritonavir, which enhances the pharmacokinetic properties of ABT-450, allowing for once-daily dosing. The use of ritonavir 100 mg with ABT-450 for the treatment of HCV is investigational.‹