(Note: the following text is an Executive Summary from our new 150-page report titled “Cancer Vaccine Therapies: Failures and Future Opportunities”)
Since the early 1990s, cancer immunotherapy has provided hope to patients, physicians, and investors as a new treatment modality with limited side effects and superior efficacy. Cancer immunotherapy broadly includes passive immunization, active immunization, and immunostimulation .
Passive immunotherapy is the transfer of an exogenous therapeutic agent to a patient where the therapy has a direct pharmacological action on the desired target. The best examples of passive immunotherapy are monoclonal antibodies [mAbs], which were hailed as “magic bullets” when they were developed in the 1970s.
Clinical results with mAbs were largely disappointing for the first 10 years of development. In fact, it wasn’t until November 1997 that the first mAb for cancer therapy, Rituxan® [rituximab], was approved by the U.S. Food and Drug Administration [FDA]. Developed by IDEC Pharmaceuticals, Rituxan® is a chimeric monoclonal antibody against the protein CD20 that is currently approved for the treatment of chronic lymphocytic leukemia [CLL], non-Hodgkin’s Lymphoma [NHL], and rheumatoid arthritis [RA].
After reporting its first year of profitability in 1998, shares of IDEC Pharmaceuticals traded at a new all-time high of $140 with a market capitalization above $3.3 billion. Worldwide net sales of Rituxan reached $1.5 billion in 2002 and the following summer IDEC Pharmaceuticals acquired Biogen, Inc. in a stock transaction valued at approximately $6.65 billion to create Biogen Idec, Inc. (NASDAQ:BIIB).
While the success of Rituxan spurred the development of other anti-CD20 mAbs, it wasn’t until October 2009 that Arzerra® [ofatumumab] was approved by the FDA for the treatment of CLL. Ofatumumab, which was developed by Genmab A/S (OTC:GNMSF) and GlaxoSmithKline plc (NYSE:GSK), is a human mAb that targets an epitope different from Rituxan® and other anti-CD20 mAbs.
Today, passive immunotherapies represent one of the most successful therapeutic classes and there are currently ten mAbs approved for cancer therapy [see Figure 1: FDA Approval of cancer mAbs from 1997-2010]. Three blockbuster products sold by the Roche Group (OTCQX:RHHBY) – Avastin® [bevacizumab], Rituxan®, and Herceptin® [trastuzumab] – collectively represented nearly US$17 billion in revenue for 2009. As useful as many of these mAbs have become in cancer therapy, they often have the greatest efficacy impact when used in combination with other therapeutic modalities, particularly cytotoxic agents.
Figure 1: FDA Approval of cancer mAbs from 1997-2010 (Click to enlarge)
Similar to passive immunotherapy with mAbs, the early development of active immunotherapies has proven to be an enormous challenge. In fact, we identified nearly a dozen product candidates that failed in Phase III trials.
Active immunotherapies are therapies that contain a specific antigen or set of antigens that are designed to activate the patient’s own immune system to seek out and destroy cells that carry the same antigen. They have no direct therapeutic action, but rather rely on the patient’s immune system to recognize and destroy the intended target.
While no active immunotherapeutics are currently approved for the treatment of cancer, the FDA has assigned a Prescription Drug User Fee Act [PDUFA]) date of May 1, 2010, by which time it will respond to Dendreon Corporation’s (NASDAQ:DNDN) amended Biologics License Application [BLA] for Provenge® [sipuleucel-T]. Dendreon is seeking licensure for Provenge® for men with metastatic castrate-resistant prostate cancer [CRPC]. This event has reignited enthusiasm for the field of active immunotherapy and shares of Dendreon, which traded below $5 in March 2009, recently hit all-time highs above $40 and a market capitalization greater than $5 billion.
As with any first-in-class product, regulatory delays are possible. For example, the BLA for Rituxan® was originally submitted on February 28, 1997, and the FDA requested additional data on certain aspects of the production process related to the bulk drug manufacture on August 29, 1997, which delayed approval until later that year [November 26, 1997]. In view of the complexities of manufacturing and distributing an autologous cancer therapy, a similar request by FDA for Provenge would not be unexpected and would likely occur around the PDUFA date using Rituxan’s history as a guide.
If approved by the FDA, Provenge would represent the first active immunotherapy for the treatment of cancer. However, unlike Rituxan’s market monopoly that lasted for nearly 12-years, Provenge could face competition in a relatively short period of time. Numerous active immunotherapies are in late-stage clinical development for prostate cancer – including a promising off-the-shelf vaccine set to begin a pivotal Phase III trial in 2010. In fact, nine product candidates are in clinical trials for the treatment of prostate cancer, representing the largest therapeutic area within the active immunotherapy market
Beyond Provenge, there are a number of additional catalysts in 2010 that could ignite further interest in the field of cancer immunotherapy. Nearly 50 clinical programs involving active cancer immunotherapies are currently underway, including nearly a dozen that are in pivotal Phase III development with several BLAs planned in 2010.
For example, Bristol-Myers Squibb Company (NYSE:BMY) has announced its intent to potentially file for regulatory approval for ipilimumab [with or without vaccine therapy] in metastatic melanoma in 2010 and has submitted Phase III data for presentation at the American Society for Clinical Oncology [ASCO] annual meeting held June 4-8, 2010. In addition, GlaxoSmithKline plc is conducting the largest ever Phase III clinical trial in lung cancer treatment with its investigational MAGE-A3 ASCI immunotherapy, with the possibility for data presentation at ASCO 2010. Lastly, following the presentation of positive Phase III trial results at ASCO 2009, Biovest International, Inc. (OTC:BVTI) expects to file a BLA for BiovaxID in NHL in 2010.
Accordingly, in our latest industry report titled “Cancer Vaccine Therapies: Failures and Future Opportunities,” we provide an overview of the cancer immunotherapy market, including interviews with several key opinion leaders and a review of the scientific, medical, clinical, and financial aspects of the major industry participants.
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