Replies to post #83862 on Biotech Values

[DewDiligence]

AMGN’s D-mab data reported today in the “mixed cancer” trial are additional color on the top-line results announced in August. From #msg-40166756:

The phase-3 denosumab trial in miscellaneous (non-breast, non-prostate) cancer showed statsig non-inferiority to Zometa; however, unlike the phase-3 trial in breast cancer (#msg-39343263), D-mab missed showing statsig superiority to Zometa by a whisker (p=0.06). The hazard ratio for the primary endpoint (time to first skeletal event) was 0.84 in the miscellaneous-cancer trial and 0.82 in the breast trial. (The phase-3 trial of D-mab vs Zometa in HRPC is in progress with data on the primary endpoint expected in 1Q10.)

…All told, the miscellaneous-cancer trial is a strong result for AMGN, although NVS dodged a bullet by the trial’s failure to show statsig superiority for D-mab.

Denosumab has the tentative brand name, Prolia; the PDUFA date for the lead indication in osteoporosis is 10/19/09. #msg-39386685 is a good read on the marketing task that confronts AMGN, assuming FDA approval.

[DewDiligence]

Denosumab Phase-3 Scorecard

[The trial in the limelight today is in the second row of the table.]


The phase-3 denosumab program is one of the largest ever
conducted for any drug by any company. All told, there are
22 phase-3 trials spanning numerous indications (although
some of them are open-label extension trials to assess long-term
safety that are effectively phase-4’s). The following table includes
the most consequential phase-3 trials; they fall into three main
groups: metastatic cancer, non-metastatic cancer, and post-
menopausal osteoporosis.

 
                            Primary   No. of  Completion  
 Indication         Comprtr Endpoint Patients   Date*    Outcome  Link  
 Met BCa            Zometa   TTFSE     2,049   compltd   superior http://clinicaltrials.gov/ct2/show/NCT00321464  
 Misc met cancer    Zometa   TTFSE     1,779   compltd   non-infr http://clinicaltrials.gov/ct2/show/NCT00330759  
 HRPC               Zometa   TTFSE     1,904     3/10      n/a    http://clinicaltrials.gov/ct2/show/NCT00321620  
 HRPC               placebo  PFS       1,435     5/10      n/a    http://clinicaltrials.gov/ct2/show/NCT00286091  
  
 Non-met BCa        placebo† TTFF      2,800     3/12      n/a    http://clinicaltrials.gov/ct2/show/NCT00556374  
 Non-met PCa        placebo‡ BMD       1,468   compltd   success  http://clinicaltrials.gov/ct2/show/NCT00089674  
 nmBCa/osteopenia   placebo  bone loss   252   compltd   success  http://clinicaltrials.gov/ct2/show/NCT00089661  
    
 1-line osteoprsis  placebo  fractures 7,200   compltd   success  http://clinicaltrials.gov/ct2/show/NCT00089791  
 1-line osteoprsis  Fosamax  BMD       1,189   compltd   success  http://clinicaltrials.gov/ct2/show/NCT00330460  
 2-line osteoprsis  Boniva   BMD         800     3/11      n/a    http://clinicaltrials.gov/ct2/show/NCT00936897  
 Osteopenia         placebo  BMD         332   compltd   success  http://clinicaltrials.gov/ct2/show/NCT00091793  
 Fosamax switch     Actonel  BMD         800     9/11      n/a    http://clinicaltrials.gov/ct2/show/NCT00919711  
 Fosamax switch     placebo  BMD         504   compltd   success  http://clinicaltrials.gov/ct2/show/NCT00377819  
    
 *For analysis of primary endpoint.  
 †All patients receive an aromatase inhibitor.  
 ‡All patients receive androgen-deprivation therapy.