Tadalafil is a PDE5 inhibitor. It is current marketed in pill form for treating erectile dysfunction (ED) but has been used for other conditions. It initially was developed by the biotechnology company ICOS, and then again developed and marketed world-wide as Cialis, by Lilly ICOS, LLC, the joint venture of ICOS Corporation and Eli Lilly and Company. Cialis tablets, in 5 mg, 10 mg, and 20 mg doses, are yellow, film-coated, and almond-shaped.

In December 2003, the Food and Drug Administration approved tadalafil (as Cialis) for sale in the U.S. as the third ED prescription drug pill after sildenafil (Viagra) and vardenafil (Levitra). Cialis's 36-hour effectiveness earned it the nickname, "The Weekend Pill"; like sildenafil and vardenafil, tadalafil is recommended as an 'as needed' medication. Cialis is the only one of the three that is also offered as a once daily medication.

Moreover, besides ED, tadalafil for the treatment of pulmonary arterial hypertension is currently under regulatory review in multiple regions. In late November 2008, Eli Lilly sold the exclusive rights to commercialize tadalafil for pulmonary arterial hypertension in the United States to United Therapeutics for an upfront payment of $150 million.

History

The FDA's approval of Viagra on 27 March 1998 was a ground-breaking commercial event for the treatment of ED, with sales exceeding one billion dollars. Subsequently, the FDA approved Levitra (vardenafil) on 19 August 2003, and Cialis (tadalafil) on 21 November 2003.

Cialis was discovered by Glaxo Wellcome (now GlaxoSmithKline) under a partnership between Glaxo and ICOS to develop new drugs that began in August 1991. In 1993, the Bothell, Washington, biotechnology company ICOS Corporation began studying compound IC351, a phosphodiesterase type 5 (PDE5) enzyme inhibitor. In 1994, Pfizer scientists discovered that sildenafil citrate, which also inhibits the PDE5 enzyme, caused penile erection in men participating in a clinical study of a heart medicine. Although ICOS scientists were not testing compound IC351 for treating ED, they recognized its potential usefulness for treating said disorder. Soon, in 1994, ICOS received a patent for compound IC351 (structurally unlike sildenafil and vardenafil), and Phase 1 clinical trials began in 1995. In 1997, the Phase 2 clinical studies were initiated for men experiencing ED, then progressed to the Phase 3 trials that supported the drug's FDA approval. Although Glaxo had an agreement with ICOS to share profits 50/50 for drugs resulting from the partnership, Glaxo let the agreement lapse in 1996 as the drugs developed were not in the company's core markets.

In 1998, ICOS Corporation and Eli Lilly and Company formed the Lilly ICOS, LLC, joint venture company to further develop and commercialize tadalafil as a treatment for ED. Two years later, Lilly ICOS, LLC, filed a New Drug Application with the FDA for compound IC351 (under the tadalafil generic name, and the Cialis brand name). In May 2002, Lilly ICOS reported to the American Urological Association that clinical trial testing demonstrated that tadalafil was effective for up to 36 hours, and one year later, the FDA approved tadalafil. One advantage Cialis has over Viagra and Levitra is its 17.5-hour half-life (thus Cialis is advertised to work for up to 36 hours, after which time there remains approximately 25 percent of the absorbed dose in the body) when compared to the four hour half–life of sildenafil (Viagra).