Replies to post #90335 on Biotech Values

[DewDiligence]

AMGN Submits Denosumab BLA for Prevention of Bone Metastases

[This BLA is supported by the three successful phase-3 studies shown in the first three rows of the table in #msg-46432335: one study in breast cancer, one in prostate cancer, and one in miscellaneous cancers; in each of these studies, Denosumab was superior or non-inferior to NVS’ Zometa on the primary endpoint of “time to first skeletal event.” (A fourth phase-3 trial, where Denosumab is being compared to placebo in HRPC, has not yet reported data.)

This PR does not say when AMGN will submit a Denosumab BLA for the prevention of fractures in *non*-metastatic cancer (see rows 5-7 in the table in #msg-46432335). I presume that submission will be made after the breast-cancer trial in row 5 of the table reports data in 2012.

For cancer indications, AMGN is evidently not planning to use the Prolia brand name that’s been selected for Denosumb in the osteoporosis indication. From a marketing standpoint, I can see why AMGN would want to keep the brands distinct— prescribing a “cancer drug” to treat osteoporosis might scare off some doctors and patients.

The Denosumab BLA in cancer will have a PDUFA date in Nov 2010 or Mar 2011 depending on whether the FDA conducts a priority or a standard review. The PDUFA date for the osteoporosis indication, which is already on the second review cycle, is 7/25/10.]

http://finance.yahoo.com/news/Amgen-Submits-Denosumab-prnews-831971912.html?x=0&.v=1

›Friday May 14, 2010, 4:03 pm EDT

THOUSAND OAKS, Calif., May 14 /PRNewswire-FirstCall/ -- Amgen Inc. (Nasdaq:AMGN - News) today announced the submission of a Biologics License Application (BLA) to the U.S. Food and Drug Administration (FDA) for denosumab, a subcutaneous RANK Ligand inhibitor. The BLA submission summarizes clinical experience from nearly 6,900 patients across 18 clinical studies, including approximately 5,700 patients with advanced cancer in the three, pivotal, Phase 3, head-to-head trials versus Zometa® (zoledronic acid).

Bone metastases, the spread of tumors to the skeleton, are a serious concern for many patients with advanced cancer. When cancer spreads to the bone, the growing cancer cells weaken and destroy the bone around the tumor, often producing serious clinical consequences such as fractures, spinal cord compression, or the need to receive radiation or surgery to bone. These events are collectively called skeletal-related events (SREs). The RANK/RANKL pathway is believed to play a central role in cancer-induced bone destruction, regardless of cancer type. Denosumab is the first therapy to target this important pathway.

"We believe that denosumab will offer substantial benefit to cancer patients suffering from bony metastases," said Roger M. Perlmutter, M.D., Ph.D., executive vice president of Research and Development at Amgen. "Denosumab, administered monthly as a 120 mg dose subcutaneously, demonstrated consistently similar or greater efficacy in clinical trials when compared to zolendronic acid, offering the potential to improve on the current standard of care. One potential advantage of denosumab is that dose adjustments resulting from declining renal function are not necessary."

Amgen intends to submit marketing applications shortly in the European Union, Switzerland, Canada and Australia, and also in Japan, working with its licensing partner, Daiichi-Sankyo. Amgen and Daiichi-Sankyo Company, Limited, have a collaboration and license agreement for the development and commercialization of denosumab in Japan.

This BLA represents the second marketing application for denosumab that has been submitted to FDA; denosumab is currently being reviewed under the trade name Prolia™ for conditions related to bone loss. For that application, the FDA has set a corresponding Prescription Drug User Fee Act (PDUFA) action date of July 25, 2010.

Bone Metastases: Prevalence and Impact

Bone metastases occur in more than 1.5 million patients with cancer worldwide and are most commonly associated with cancers of the prostate, lung, and breast, with incidence rates as high as 75 percent of patients with metastatic disease(i).

The economic burden of U.S. patients with bone metastases is significant and is estimated to be $12.6 billion annually(ii). Patients with bone metastases who experience an SRE incur significantly higher medical costs compared with those who do not experience an SRE(iii).

About Denosumab and Amgen's Research in Bone Biology

Denosumab is the first fully human monoclonal antibody in late stage clinical development that specifically targets RANK Ligand, the essential regulator of osteoclasts (the cells that break down bone). The denosumab development program is the largest ever initiated by Amgen. This broad and deep development program demonstrates Amgen's commitment to researching and delivering pioneering medicines to patients with unmet medical needs. Amgen is studying denosumab in numerous tumor types across the spectrum of cancer-related bone diseases. Over 11,000 patients have been enrolled in the denosumab oncology clinical trials, testing the drug for the reduction of SREs in patients with breast and prostate cancer, as well as other solid tumors and multiple myeloma, for the amelioration of treatment-induced bone loss in patients with non-metastatic breast or prostate cancers, and for its potential to delay bone metastases in prostate cancer.‹

[DewDiligence]

Denosumab Phase-3 Scorecard

[New completion date for HRPC trial in prevention of bone
mets (from disclosures at AMGN’s ASCO webcast on 6/7/10).]


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
(although some 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 four main groups:
metastatic cancer/treatment of bone mets; metastatic cancer/prevention
of bone mets; preservation of bone health in non-metastatic cancer; and
postmenopausal osteoporosis.

 
                            Primary   No. of  Completion   
 Indication         Comprtr Endpoint Patients   Date*    Outcome  Link   
  
 Metastatic cancer – treatment of bone metastases: 
 Breast cancer      Zometa   TTFSE     2,049   compltd   superior http://clinicaltrials.gov/ct2/show/NCT00321464   
 HRPC               Zometa   TTFSE     1,904   compltd   superior http://clinicaltrials.gov/ct2/show/NCT00321620   
 Misc. cancers      Zometa   TTFSE     1,779   compltd   non-infr http://clinicaltrials.gov/ct2/show/NCT00330759   
  
 Metastatic cancer – prevention of bone metastases:  
 HRPC               placebo  PFS       1,435     4Q10      n/a    http://clinicaltrials.gov/ct2/show/NCT00286091   
    
 Non-metastatic cancer – preservation of bone health:  
 Breast cancer      placebo† TTFF      2,800     1Q12      n/a    http://clinicaltrials.gov/ct2/show/NCT00556374   
 Prostate cancer    placebo‡ BMD       1,468   compltd   superior http://clinicaltrials.gov/ct2/show/NCT00089674   
 BCa w osteopenia   placebo  bone loss   252   compltd   superior http://clinicaltrials.gov/ct2/show/NCT00089661   
      
 Treatment/prevention of post-menopausal osteoporosis: 
 1-line osteoprsis  placebo  fractures 7,200   compltd   superior http://clinicaltrials.gov/ct2/show/NCT00089791   
 1-line osteoprsis  Fosamax  BMD       1,189   compltd   superior http://clinicaltrials.gov/ct2/show/NCT00330460   
 2-line osteoprsis  Boniva   BMD         800     1Q11      n/a    http://clinicaltrials.gov/ct2/show/NCT00936897   
 Osteopenia         placebo  BMD         332   compltd   superior http://clinicaltrials.gov/ct2/show/NCT00091793   
 Fosamax switch     Actonel  BMD         800     3Q11      n/a    http://clinicaltrials.gov/ct2/show/NCT00919711   
 Fosamax switch     placebo  BMD         504   compltd   superior http://clinicaltrials.gov/ct2/show/NCT00377819 

*For analysis of primary endpoint.
†All patients receive an aromatase inhibitor.
‡All patients receive androgen-deprivation therapy.