The drug discovery and development process is a difficult one that takes considerable expertise in both the research and business realms. Seattle (and the rest of Washington state) currently has approximately 112 drug-focused biotechnology companies, 17 of which are publicly traded either in the U.S. or Japan. The area also has a number of non-profit research organizations that participate in a variety of efforts to find new medicines. Biotech companies have been operating here for some 35 years, during which time about 109 of them have either been acquired, merged, moved out of town, or gone out of business. So what are the prospects for developing new drugs here in Seattle? To address this question, I thought it might be helpful to look back at the track record of our local biotechs. Just how many drugs have we developed locally?
Answering this question turned out to be anything but simple. Some drugs were discovered and developed here, some were discovered elsewhere but were developed for different diseases by Seattle companies, and others were simply acquired and then sold by our local biotechs. There are a few other caveats I should point out. First, most of these drugs were developed with the help and financial assistance of Big Pharma partners. Second, biotechnology formed the technology base that several companies used to develop non-drug medical products that won FDA approval, as noted below. Finally, I want to acknowledge that there have been a number of successes locally in medical devices, agricultural biotech, diagnostics, and biocomputing software applications. However, my focus today is on drug discovery and development. Let’s take a look back and see where we’ve been:
Nine Drugs Discovered and Developed by Seattle Biotechs
Sargramostim (Leukine) was developed by Immunex to stimulate the proliferation of white blood cells in patients recovering from bone marrow transplants. It won FDA approval in 1991. Sargramostim only captured a small share of the market due to stiff competition from Amgen’s competing drug filgrastim (Neupogen), which was approved a month earlier by the FDA to treat a much larger group of patients recovering from chemotherapy. Amgen’s purchase offer for Immunex led to the divestiture (for antitrust reasons) of sargramostim to Berlex, the U.S. subsidiary of Schering AG. Bayer subsequently acquired Berlex in 2006, and then sold sargramostim to Genzyme in 2009. Sanofi acquired Genzyme in 2011 and is currently selling the drug.
Etanercept (Enbrel) was originally developed by Immunex for treating sepsis, but failed in clinical trials. While most companies would have buried a failed drug, Immunex resurrected etancercept by testing it in rheumatoid arthritis patients. Strongly positive results led to FDA approval in 1998, and the drug has since been cleared to treat a number of disorders, including juvenile rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, and plaque psoriasis. Acquiring etanercept was the main reason Amgen bought Immunex in 2002. Etanercept went on to become one of the best selling biologic drugs in the world, with worldwide sales in 2014 of $8.78 billion. Amgen’s purchase of Immunex also brought on board the monoclonal antibody that would become panitumumab (Vectibix), and prevented a nasty patent war between the companies over intellectual property that led to the osteoporosis drug denosumab (Prolia). Amgen downsized Immunex’s operations after buying the company, and eventually closed its two research facilities in Washington state in 2015.
Tadalafil (Cialis) was initially discovered by Glaxo Wellcome (now GlaxoSmithKline) as part of a partnership with Icos. Glaxo wound up bailing out on tadalafil because the drug didn’t fit into its corporate strategy at the time. Icos then teamed up with Eli Lilly to develop and commercialize the molecule; it won FDA approval in 2003 for the treatment of erectile dysfunction. Eli Lilly went on to acquire Icos in 2007 and close down the company. Tadalafil was later approved for the treatment of pulmonary arterial hypertension in 2009, and for the treatment of benign prostatic hyperplasia in Oct. 2011.
Abatacept (Orencia) is used to treat rheumatoid arthritis in patients not responding to anti-TNF therapies like etanercept (Enbrel) or adalimumab (Humira). It received FDA approval in 2006. What is not well known is that abatacept arose from work done here in Seattle at the Bristol-Myers Squibb Pharmaceutical Research Institute. Bristol closed down the Seattle branch of its Research Institute in 1997, and the development work was transferred to other parts of the company.
Zymogenetics’ recombinant human thrombin (Recothrom) was approved by the FDA in 2008 as a topical treatment for surgical bleeding. It was developed as part of a safety-driven trend in biotechnology in which recombinant human proteins replaced ones that used to be purified from either animal or human sources. Other examples include insulin, hemophilia proteins, and growth hormone. Zymogenetics initially partnered with Bayer in 2007 to sell the drug, but regained the rights two years later when Bayer walked away from the deal. After Bristol acquired Zymogenetics 2010, it entered into an agreement in 2012 that allowed The Medicines Co. to sell Recothrom globally.
Dendreon’s sipuleucel-T (Provenge) won FDA approval in April of 2010 to treat metastatic hormone-refractory prostate cancer. It should be noted that sipuleucel-T is not a classic drug per se because it is not directly administered to patients. Instead, it is a method of treating a patient’s cells outside of their body, and then reinfusing them to stimulate their immune system to battle the prostate cancer cells. Unfortunately, the high cost of the drug, its limited effectiveness, competition from more convenient pills, and the expense of custom generating each patient’s treatment led Dendreon to declare bankruptcy in Nov. 2014. Valeant Pharmaceuticals subsequently purchased Dendreon in Feb. 2015 for $495 million. Dendreon’s initial clinical success with sipuleucel-T triggered a tsunami of activity by other biotechs in the area of cancer immunotherapy, which has been in and out of favor for over a century.
Amgen’s denosumab (Prolia) was FDA approved in June 2010 for postmenopausal osteoporosis. Both Immunex and Amgen invested considerable research efforts into the discovery of a protein, RANK ligand, that plays a key role in the biological process of bone remodeling. This ultimately led Amgen (after it acquired Immunex) to develop the monoclonal antibody denosumab, which binds to and inhibits the activity of this protein.
In 2010, denosumab was also approved for patients with bone metastases of solid tumors (such as prostate cancer), and who are at high risk of bone fractures. It’s marketed to these patients under the name Xgeva.
Calistoga Pharmaceuticals was one of the first virtual biotech companies, created out of Icos (shortly before that company was acquired by Eli Lilly in 2006) to develop a cancer drug that inhibited the delta isoform of the enzyme PI3 kinase. Gilead bought Calistoga in February 2011 in order to acquire the rights to this drug. Named idelalisib (which Gilead markets as Zydelig), it received … Next Page »