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Original Source: FD (FAIR DISCLOSURE) WIRE
. Will Roberts, ViroPharma, Director of Corporate Communications . Michel de Rosen, ViroPharma, CEO . Colin Broom, ViroPharma, Chief Scientific Officer . Joe Slavinsky, Thomas Weisel Partners, Analyst
. Kevin Tang, Tang Capital, Analyst . Wayne Rothbaum, Quo Capital, Analyst . Meg Malloy, Goldman Sachs, Analyst . Joel Sendek, Lazard Capital, Analyst . Thomas Wei, Piper Jaffray, Analyst . Vinnie Milano, ViroPharma, CFO, COO
The Co. announced preliminary results from a Phase 2 study with maribavir, an oral antiviral drug candidate. This represents VPHM's hope for maribavir that it will be a highly active drug against the virus in humans supporting it uses prophylaxis to prevent CMV reactivation and it will have a more benign toxicity profile vs. currently available drugs.
S1. Opening Comments (M.D.) 1. Phase 2 Study of Maribavir: 1. This study showed that maribavir effectively and dramatically
reduced the rate of cytomegalovirus or CMV reactivation in allogeneic stem cell transplant patients. 2. The Co. achieved statistically significant results in the 2b [Ig] arms for the protocol defined primary efficacy endpoint, which was CMV reactivation rates using the pp65 antigen assay. 3. Overall, this trial showed that maribavir reduced the incidence of CMV reactivation in all doses tested vs. the placebo group and in almost all cases in a statistically significant manner. 4. The tolerability profile of the drug was excellent. 5. VPHM acquired maribavir in 2003 from GlaxoSmithKline. 1. GSK had done extensive work with the drug assessing its activity against CMV but in a disease known as CMV retinitis, which used to be a prevalent disease affecting
the eyes and vision of patients suffering from HIV and AIDS.
2. With the advent of very powerful anti-HIV cocktail therapies through the nineties the disease less of a problem.
S2. Maribavir Phase 2 Results (C.B.) 1. Maribavir Preliminary Phase 2 Study: 1. Demonstrated significant antiviral activity leading to a clinically meaningful reduction in CMV infection or viral
reactivation. 2. Maribavir demonstrated a favorable tolerability profile even in the very sick stem-cell transplant patient population.
1. The only cases of CMV disease occurred in the control group.
2. There were no cases of this life threatening disease in subjects who received maribivar. 3. Maribavir may prove to be paradigm-changing drug allowing for wider use of a prophylactic treatment strategy compared through observations and pre-emptive treatment as the viral replication has been identified in this high-risk operation.
2. Study Design: 1. This trial was a randomized, double blind, placebo-controlled, dose-ranging study at 13 leading transplant centers across the US and recruited CMV seropositive subjects, that is patients with known previous infection with CMV.
1. Each of these had undergone a successful allogeneic stem cell or bone marrow transplant from a donor. 2. A total of 111 subjects were enrolled in three ascending dose cohorts with each cohort subject to randomized 3:1 to receive maribavir or placebo treatment.
1. This means that 28 patients were given placebo and the remaining patients were in three maribavir treatment groups of 27 or 28 patients each. 3. The study used three ascending dose regimens of maribavir.
1. The lowest dose, 100 mg twice daily. 2. 400 mg once daily. 3. Top dose, 400 mg twice daily. 4. Treatment was up to 12 weeks in duration. 1. This treatment period encompasses the 100 days post-transplant period that is considered to represent a period of highest risk for reactivation of CMV infection and for the development of CMV disease. 5. All subjects were monitored weekly with blood tests to test CMV infection using both pp65 antigen tests and PCR. 1. If CMV was detected at any point, study drug meaning marivabir or placebo was discontinued and the subject was managed according to current standards of care at each transplant center, which included pre-emptive anti-CMV treatment usually with intravenous ganciclovir. 3. Four Objectives of the Study: 1. To evaluate: 1. Safety and tolerability of maribavir administered orally for up to 12 weeks. 2. The prophylactic activity of maribavir in preventing CMV reactivation. 3. The pharmacokinetics of marivabir in the subject population. 4. To select a dose or doses to be used in the Phase 3 program. 2. The expectation was that, based on previously published data, the placebo group would show a CMV reactivation rate of approx. 60%. 4. Antiviral Activity of the Drug: 1. In an intent-to-treat analysis all patients randomized to treatment are included in the analysis. 2. In an analysis of the first 100 days post-transplant, the number of subjects who required pre-emptive anti-CMV therapy was reduced significantly in each of the maribavir groups vs. the placebo group. 1. In the placebo, 57% of patients required pre-emptive
anti-CMV therapy, which is consistent with what the Co. expected based on historical data. 3. The maribavir treatment groups, 100 mg BID, 400 mg QD, and 400 mg BID, had lower rates of 15%, 30%, and 15% respectively. 1. These reductions were statistically significant with p values in this analysis for each maribavir dose groups vs. placebo rating from 0.051-0.001. 2. There are number of ways to look at the data and also a number of methods can be used to detect CMV reactivation. 1. The Co. used the pp65 antigen assay or PCR to detect viral DNA or both. 3. Irrespective of the method used to detect CMV reactivation, the differences between maribavir and placebo are consistent and in most cases statistically significant.
4. There were no cases of CMV disease in any of the maribavir
groups. 5. Whereas, CMV diseases was reported in three patients or 11% of placebo groups. 1. Although, not statistically …