Replies to post #100642 on Biotech Values

[DewDiligence]

Correction re link to the PROVE-3 results in my prologue annotations of today’s Boceprevir PR: the Telaprevir PROVE-3 data (for comparing to the Boceprevir RESPOND-2 data) can be found at #msg-48759554.

[DewDiligence]

Telaprevir vs Boceprevir in First- and Second-Line Settings

 
                                       SVR in best     SVR in      SVR   iHub 
 Trial design      Setting   Acronym  treatment arm  control arm  Delta  reference  
 SoC ± Telaprevir  1st-line  ADVANCE   *75% (n=362)  44% (n=369)   31%   #msg-50595752 
 Soc ± Boceprevir  1st-line  SPRINT-2  †66% (n=366)  38% (n=366)   28%   #msg-52949888 
  
 SoC ± Telaprevir  2nd-line  PROVE-3   ‡53% (n=151)  14% (n=151)   39%   #msg-48759554 
 Soc ± Boceprevir  2nd-line  RESPOND-2 †66% (n=134)  21% (n=134)   45%   #msg-52949888 

* ‘12+12’ arm. (SVR in ‘8+16’ arm was 73%.)

† 48w arm with 4w lead-in on SoC alone. (SVR in ‘response-guided’ arm
was 63% in SPRINT-2 and 59% in RESPOND-2.) No breakdown of patients
by response to first-line treatment is available for RESPOND-2 at this time.

‡ ’24+24’ arm. (SVR in ‘12+12’ arm was 51%.) 57% of patients were prior
non-responders, 7% were prior breakthroughs, and 36% were prior relapsers.

[DewDiligence]

Addendum re the Boceprevir RESPOND-2 study in the second-line setting: In the prologue of #msg-52949888, I said:

…the Boceprevir RESPOND-2 study may have had an easier-to-treat patient pool than the Telaprevir PROVE-3 study in terms of the proportion of patients who were relapsers vs non-responders during prior treatment; VRTX disclosed the relapser-vs-non-responder breakdown from PROVE-3 in #msg-48759554, but MRK is refusing to disclose the breakdown from RESPOND-2 until the full dataset is presented at AASLD.

I was being too gentle on MRK by using the word may in the above passage. Based on the eligibility requirements for RESPOND-2, it’s clear that RESPOND-2 did in fact have an easier-to-treat patient pool than VRTX’s PROVE-3 study. From the clinicaltrials.gov entry for RESPOND-2:

http://clinicaltrials.gov/ct2/show/NCT00708500

Inclusion Criteria:

• Qualifying regimen defined as peginterferon alfa-2a plus ribavirin or peginterferon alfa-2b plus ribavirin for a minimum of 12 weeks.

• During qualifying regimen, subjects must have either a documented undetectable HCV-RNA within 30 days of end of treatment (EOT) and a subsequent detectable HCV-RNA during follow-up or a documented decline in HCV-RNA by >=2 log10 by Treatment Week 12

In other words, so-called null responders during first-line therapy were ineligible for enrollment in RESPOND-2.

MRK’s assertion that 25% of the patients in RESPOND-2 are considered null responders based on their lack of a 1-log viral-load decline during the 4-week SoC lead-in period in RESPOND-2 is therefore nothing but spin, IMO.