Replies to post #77064 on Biotech Values

[DewDiligence]

Answer to VRTX Telaprevir quiz:

“Delayed start arm [the ‘lead-in’ idea premiered by SGP], comprised of 4 weeks of treatment with peg-IFN and RBV, followed by telaprevir dosed at 750 mg q8h for 12 weeks in combination with standard doses of peg-IFN and RBV, followed by another 32 weeks of peg-IFN and RBV alone.”

Correct—the above refers to the “4+12+32” arm in the phase-3 REALIZE study in the second-line setting (#msg-32901932). It is hoped that the 4-week “lead-in” period without Telaprevir will prevent or lessen the severity of Telaprevir-induced rash.

In summary, the two trial-design wrinkles in the phase-3 Telaprevir program that may help lessen the impact of rash are: i) the “8+16” arm in the ADVANCE study, which shortens the duration of Telaprevir treatment from 12 weeks to 8 weeks; and ii) the “4+12+32” arm in the REALIZE study, which defers the start of Telaprevir treatment by 4 weeks and thereby allows the patient to attain a steady-state concentration of interferon and ribavirin before adding Telaprevir to the cocktail.

[exwannabe]

Re: I think that ribavirin is almost as guilty

So why are these trials being designed to avoid the rash when rib is in both arms?

[iwfal]

(I think that ribavirin is almost as guilty), then you might think that this would be beneficial, a delayed start in the use of telaprevir.....

Not likely that ribavirin is almost as guilty as telaprevir for the AE, at least the serious AE:

Grade 3 rash was observed in 7 (6%), 5 (4%), 6 (5%) and 1 (1%) patients in T12/PR24, T24/PR48, T24/P24, and PR48, respectively. Grade 3 anemia was observed in 0 (0%), 7 (6%), 1 (1%) and 1 (1%) patients in T12/PR24, T24/PR48, T24/P24 and PR48, respectively. Eleven (10%), 29 (25%), 10 (9%), and 5 (4%) patients discontinued due to AEs in T12/PR24, T24/PR48, T24/P24, and PR48, respectively.

Note the much greater incidence of rash in the telaprevir arms than in the no-telaprevir arm. Same with the discontinuation due to AEs.