The crisis in the pharmaceutical industry is generating a serious search for new business models. Manufacturers are looking to partner more with small biotechnology firms and academic research institutes, to shift research and production operations overseas, and to streamline operations and reduce waste wherever possible. The National Institutes of Health (NIH) proposes to ramp up support for translational medicine that will shepherd basic research through the R&D "valley of death" to yield new therapies. Patient advocacy groups are consulting with and providing funding for public and private therapy development programs. America's position as the world leader in biomedical R&D is "under siege today," and facing its biggest threat in 65 years, commented former Congressman John Porter, at a forum in March 2011, sponsored by ResearchAmerica. "Is America going to put progress on hold?" he asked in calling for decision-makers to consider the importance of science and innovation in making spending decisions. These trends are shaping many aspects of biopharmaceutical development, production, and marketing.
SLOWDOWN AT FDASome of the blame for longer, more costly drug development falls on the shoulders of FDA. Stepped-up demand for more safety and efficacy data, prior to approval as well as after a drug comes to market, can add to development costs, and ultimately weaken less robust pharmaceutical R&D programs. Moreover, success rates remain notably low for new drugs in clinical development, despite years of efforts to better inform the clinical-research process to avoid wasting millions of dollars on unsuccessful studies. The Biotechnology Industry Organization (BIO) reported in February that only one in ten new drugs make it from Phase I studies to FDA approval, based on an analysis of thousands of drug-development efforts from 2003 through 2010.
Most disappointing is an actual decline in new drug approvals by FDA last year, a troubling shift after two years of slight increases. The agency cleared only 21 new molecular entities (NMEs) in 2010, down from 25 in 2009. Even more discouraging are reports that fewer applications for innovative new therapies were filed with FDA last year, squelching optimism about an upturn in product approvals in the near future. Yet, FDA is caught in a hard place, as patient advocates demand earlier access to promising therapies, while policymakers and consumer groups insist on more scrutiny of test products to better detect potential safety problems.
The approval downturn kept several highly touted experimental products from the market. Cardiovascular safety issues prompted FDA to reject new diabetes therapies and kill several new weight-loss drugs, while also pulling Abbott's Meridia product from the market. More recently, a promising fast-acting inhaled insulin product (MannKind's Afrezza) was put on hold following FDA requests for more data on product usage and safety. The agency drew heat for turning down an application from Cell Therapeutics for pixantrone, a treatment for non-Hodgkin's lymphoma that showed some efficacy, but not enough for FDA approval. Cancer advocates continue to oppose a move by FDA to narrow its approved indication for Avastin, insisting that the benefits outweigh new evidence of serious side effects.
There are some bright spots amidst these disappointments. Last month, FDA approved a new treatment for melanoma, Bristol-Myers Squibb's (BMS) Yervoy (ipilimumab). The drug is the first to prolong lives of patients with this deadly skin cancer and a vast improvement over existing therapies. Even better for the manufacturer is an expectation that this new monoclonal antibody, which enlists the body's immune system to attack cancer cells, could lead to similar treatments for other cancers.
FDA also made headlines earlier this year by approving the first new treatment for lupus in more than 50 years—Benlysta (belimumab), developed by Human Genome Sciences with support from GlaxoSmithKline. The drug's discovery relied on information resulting from human genome mapping and represents the first real success in this field after multiple failures.
BMS cites its new cancer drug as evidence that an increased focus on pharma R&D can yield big dividends. "R&D pays," stated CEO Lamberto Andreotti in an interview with the Wall Street Journal, noting that the firm is investing research money very carefully in a range of disease classes and expects to have four more new therapies approved by FDA in another year. Merck similarly told Wall Street analysts in February that it's not cutting back on its $8 billion R&D spending plans, even though the decision may result in missing long-term profit forecasts.
Last year's slim drug-approval list included several notable products. Amgen won approval for osteoporosis treatment Prolia (denosumab), and Roche's Genentech brought out Actemra (tocilzumab), an intravenous drug for rheumatoid arthritis. Boehringer Ingelheim won the race to bring to market a new blood-thinner Pradaxa (dabigatron), although others may catch up soon. Probably the most exciting new product was Dendreon's therapeutic prostate cancer vaccine Provenge (sipuleucel-T). Other new vaccines for meningococcal disease and pneumococcal disease also were approved by the Center for Biologics Evaluation and Research (CBER).