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On Friday, March 25, 2011, the U.S. Food and Drug Administration [FDA] approved Yervoy® [ipilimumab] by Bristol-Myers Squibb (NYSE:BMY) for the treatment of patients with late-stage [metastatic] melanoma. With the news, ipilimumab becomes the eleventh monoclonal antibody [mAb] approved for the treatment of cancer. The first mAb approved for cancer treatment was Biogen Idec, Inc’s (NASDAQ:BIIB) Rituxan® [rituximab] back in November 1997 (click here to see graph of mAb approvals).

Approval of ipilimumab is the second victory for the field of active immunotherapy in oncology within a year. On April 29, 2010, the FDA approved the very first active immunotherapy for the treatment of cancer – Dendreon Corporation’s (NASDAQ:DNDN) Provenge® [sipuleucel-T] for metastatic castrate-resistant prostate cancer [CRPC]. The fact that two active immunotherapies have demonstrated improved survival in randomized Phase 3 trials and subsequently been approved by the FDA has reignited enthusiasm for the field of active immunotherapy, which has experienced nearly a dozen failures in Phase 3 clinical trials.

A Long Time in the Making

The idea to stimulate one’s own immune system to treat cancer dates back to 1891 when William Coley, Professor of Clinical Surgery at Cornell University, noticed the curative effect of an accidental bacterial infection in a patient with inoperable sarcoma. It would be 119 years since Dr. Coley’s discovery before the FDA approved the first active immunotherapy for the treatment of cancer.

As the scientific understanding of the immune system has significantly increased since Dr. Coley’s time, scientists and physicians developed successful immune system related strategies to fight cancer, viral infection and autoimmune diseases. Today, mAbs are among the most successful modern immunotherapies and provide clinical benefit to a vast array of diseases – with three blockbuster mAbs generating approximately $17 billion in sales in 2009.

Melanoma Losing Streak

In addition to helping renew interest in the field of active immunotherapy, the FDA’s approval of ipilimumab provides a much-needed boost to companies developing product candidates for melanoma. Among the eleven Phase 3 failures with active immunotherapies for the treatment of cancer, more than one-third of them have occurred in melanoma [see Table 1].

Table 1. Select Active Immunotherapy Failures in Phase 3 Trials

Company Product Candidate Description Result
CancerVax Canvaxin Allogeneic, whole cell tumor derived No improvement in overall survival
Progenics Pharmaceuticals, Inc. (NASDAQ:PGNX) GMK vaccine GM2 ganglioside coupled with KLH and formulated with QS-21 No improvement in relapse-free or overall survival
Corixa Melacine Allogeneic, Mel S/Mel D cell lines No improvement in relapse-free or overall survival
Agenus, Inc. (NASDAQ:AGEN), formerly Antigenics Oncophage® Autologous, whole cell tumor derived heat shock proteins No improvement in overall survival

Crowded Market

While ipilimumab is the first new drug approved for the treatment of melanoma in 13 years, there are four competitive active immunotherapy programs in Phase 3 development [see Table 2]. In fact, melanoma is second only to prostate cancer as the most crowded clinical development segment within the active immunotherapy field.

Table 2. Select Phase 3 Active Immunotherapy Product Candidates in Melanoma

Company Product Disease(s) Type Stage
Amgen (NASDAQ:AMGN) through the acquisition of BioVex Group OncoVEX[GM-CSF] Melanoma [unresectable Stage III b-c and Stage IV M1a-c], and head & neck Allogeneic, oncolytic herpes simplex virus encoding GM-CSF for direct injection into lesions Phase 3 ongoing
AVAX Technologies [AVAX.PK] MVAX Melanoma [Stage IV], and ovarian Autologous, whole cell, hapten modified SPA approved for Phase 3
GlaxoSmithKline plc (NYSE:GSK) MAGE-A3 ASCI Melanoma [metastatic – stage III-IVa progressive], and NSCLC Allogeneic, peptide Phase 3 ongoing
Vical, Inc. (NASDAQ:VICL) and AnGes Allovectin-7® Melanoma [1st line Stage III and IV] Allogeneic, DNA plasmid/lipid complex Phase 3 ongoing

Five by 2015

As highlighted in our firm’s April 2010 report titled “Cancer Vaccine Therapies: Failures and Future Opportunities,” there are a number of additional catalysts that could ignite further interest in the field of active immunotherapy for cancer. Nearly 50 clinical programs are currently underway, including nearly a dozen that are in pivotal Phase 3 development.

Using the history of passive immunotherapy development as a guide, it would not be surprising to see five active cancer immunotherapies approved within five years, which leads to our “5 x 2015″ projection. With the approvals of both sipuleucel-T and ipilimumab in hand, the next three may come from the following list of Phase 3 product candidates [in alphabetical order]:

  • Amgen (AMGN), OncoVEX[GM-CSF], melanoma and head & neck
  • AVAX Technologies [AVAX.PK], MVAX, melanoma
  • Bavarian Nordic [BAVA.CO], Prostvac®, prostate cancer
  • Biovest International (OTC:BVTI), BiovaxID®, NHL
  • Cel-Sci (NYSEMKT:CVM), multikine, head & neck
  • Celldex Therapeutics (NASDAQ:CLDX), rindopepimut/CDX-110, glioblastoma
  • GlaxoSmithKline (GSK), MAGE-A3 ASCI, NSCLC and melanoma
  • Novarx (private), Lucanix™/belagenpumatucel-L, NSCLC
  • Oncothyreon (NASDAQ:ONTY)/Merck KGaA, Stimuvax®/BLP25 liposome vaccine, NSCLC
  • Oxford BioMedica plc [OXB.L], Trovax®, renal cell
  • Transgene [TNG.PA]/Novartis (NYSE:NVS), TG4010/MVA-MUC1-IL2, NSCLC
  • Vical (VICL)/AnGes, Allovectin-7®, melanoma

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Disclosure: I have no positions in any stocks mentioned, and no plans to initiate any positions within the next 72 hours.