FDA approval of sildenafil in 1998 was a seminal commercial event for the treatment of ED, with sales exceeding $1 billion. The FDA subsequently approved vardenafil and tadalafil in 2003.
It was first developed by ICOS, a biotechnology company, and then by Lilly ICOS, LLC, a joint venture between ICOS Corporation and Eli Lilly & Company, and sold worldwide. Tadalafil was approved for pulmonary hypertension in the U.S. in 2009, and the condition is under regulatory review in other regions. In late November 2008, Eli Lilly and Company sold exclusive U.S. rights to tadalafil for pulmonary hypertension to United Therapeutics for an upfront payment of $150 million.
Tadalafil was discovered by Glaxo Wellcome (now GlaxoSmithKline) in August 1991 in a collaboration between Glaxo and ICOS to develop new drugs. In 1993, ICOS Corporation, a biotechnology company based in Bothell, Washington, began working on compound IC351, an enzyme inhibitor of phosphodiesterase type 5 (PDE5). In 1994, Pfizer scientists found that sildenafil also inhibited the PDE5 enzyme, causing penile erections in men participating in clinical trials of cardiac drugs. Although ICOS scientists did not test compound IC351 for ED, they recognized its potential use in treating the disease. Soon, in 1994, ICOS received a patent for compound IC351 (structurally different from sildenafil and vardenafil), and phase 1 clinical trials began in 1995. In 1997, a Phase 2 clinical study was initiated in men with ED and then progressed to a Phase 3 trial to support FDA approval of the drug. Although Glaxo reached an agreement with ICOS to split drug profits from the collaboration 50/50, glaxo let that deal lapse in 1996 because the drugs developed were not in the company’s core markets. In 1998, ICOS Corporation and Eli Lilly and Company formed a joint venture, Lilly ICOS, LLC, to further develop and commercialize tadalafil as a treatment for ED. Two years later, Lilly ICOS, LLC submitted a new Drug application to the FDA for compound IC351 (under the generic name Tadalafil and the brand name Cialis). In May 2002, Lilly ICOS reported to the American Urological Association that tadalafil was effective in clinical trials for up to 36 hours, and the FDA approved tadalafil a year later. One advantage of Cialis over Viagra and Levitra is its 17.5-hour half-life (hence, cialis is advertised as being able to work for up to 36 hours, after which the body retains about 25% of the absorbed dose), while these four methods compare to sildenafil (Viagra) half-life.
In 2007, Eli Lilly and Company bought the ICOS Corporation for $2.3 billion. As a result, Eli Lilly owned Cialis and then closed the ICOS operations, ending the joint venture and firing most of ICOS’s approximately 500 employees, except for 127 employees of the ICOS biologics facility, which subsequently was bought by CMC Biopharmaceuticals A/S (CMC).