Vertex Pharmaceuticals

Vertex Pharmaceuticals (Vertex) is a biopharmaceutical company with near 2,500 employees headquartered in Boston, Massachusetts.[1] They were one of the first companies to focus on rational drug design rather than combinatorial chemistry libraries and began their efforts in the viral disease space. They are best known for their therapies treating cystic fibrosis.

Vertex was founded in 1989 by organic chemist Joshua Boger from Merck with the goal of developing pharmaceuticals through rational design. Vertex sought a broad, deep scope of projects to change the drug-development landscape. During their early years, they worked with GlaxoSmithKline to develop amprenavir and fosamprenavir, two HIV protease inhibitors.[2,3]

Over a 22-year period of intense research & development from their founding in 1989 to 2011, Vertex grew a research pipeline in multiple areas that eventually culminated into a few FDA-approved pharmaceutical agents. Their first FDA-approved therapy was telaprevir, a protease inhibitor approved in 2011, for the treatment of hepatitis C.[3] Telaprevir surpassed 1 billion in sales after its first year on the market, however unforeseen side-effects and competition by Gilead & Merck reduced its sales quickly in the following months.[4] As a consequence in 2014, Vertex discontinued telaprevir.

Concurrently in 2001, Vertex acquired Aurora Biosciences, and began development of a cystic fibrosis treatment to target the cause of the disease rather than the symptoms, which would soon become its most profitable achievement. The Cystic Fibrosis foundation realized that the return of profit of such a drug would be minimal; they began one of the first examples of venture-backed philanthropic funding of a pharmaceutical agent, totaling over 70 million in support for Vertex's drugs ivacaftor, lumacaftor, and tezacaftor.[5]

Cystic fibrosis is characterized by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, which leads to a failure of the encoded protein to transport chloride ions across epithelial cell membranes. Vertex initially developed ivacaftor (Kalydeco)[6], which potentiates the mutated CFTR protein to allow for higher chloride conductance.[7] Two drugs were further developed, lumacaftor and tezacaftor, small molecule chaperones that assist with proper folding of the CFTR and trafficking to the membrane.[8,9] Lumacaftor and tezacaftor are often given as one medication (Orkambi). These medications often cost hundreds of thousands of dollars, varying by location and combination of therapeutics, and the cost is often majorly covered by insurers.[10]

Outrage concerning the company's pricing of its therapeutic agents has made its way into the mainstream. Although insurance companies can cover the majority of the high cost, many require patients to pay thousands of dollars out of pocket. A large group of physician scientists and patients with cystic fibrosis wrote to Vertex asking for a price reduction of Kalydeco from its near $300,000 per year cost, calling the drug pricing "unconscionable", and Vertex responded with an email as such: "while publicly funded academic research provided important early understanding of the cause of cystic fibrosis, it took Vertex scientists 14 years of their own research, funded mostly by the company, before the drug won approval."[11] Vertex has spent over 5 billion USD in research and development since their founding in 1989, with a significant percentage allocated towards their cystic fibrosis drugs.[11]

Vertex has also had a longstanding collaboration with CRISPR therapeutics to target other gene-based diseases such as sickle cell and b-thalassemia. Vertex recently acquired Exonics, a UTSW-based company generated from Dr. Eric Olson's gene editing technologies, to continue its adventure into CRISPR-based therapies.[12]

Barry Werth, an award-winning journalist, has followed Vertex since its inception. The history of the company from young start-up to billion-dollar behemoth is further detailed in The Billion-Dollar Molecule and in The Antidote: Inside the World of New Pharma, essential reads for those interested in pharmaceutical start-ups.