United Therapeutics has agreed to license and co-develop MannKind’s clinical-phase dry powder formulation of the pulmonary arterial hypertension (PAH) treatment treprostinil—the active ingredient in United Therapeutics’ top-selling drugs Remodulin® and Tyvaso®—through a collaboration that could generate more than $95 million for MannKind, the companies said today.
Under their worldwide exclusive licensing and collaboration agreement, United Therapeutics agreed to oversee global development, regulatory, and commercial activities involving treprostinil—while MannKind agreed to manufacture clinical supplies and initial commercial supplies of the product at its manufacturing facility in Danbury, CT. United Therapeutics also agreed to manufacture long-term commercial supplies of treprostinil.
United Therapeutics agreed to pay MannKind $45 million upfront, $50 million in payments tied to achieving development milestones, and low double-digit royalties on net sales of treprostinil.
Treprostinil is marketed by United Therapeutics as the injection drug Remodulin, and as the inhaled drug Tyvaso; both are prostacyclin vasodilators.
Remodulin is United Therapeutics’ top-selling treatment, generating sales last year of $670.9 million, up 11.4% from $602.3 million in 2016. For the first six months of this year, however, sales of Remodulin have slipped nearly 6% year-over-year, to $286.3 million from $303.5 million.
Among reasons cited by United Therapeutics for the decline in Remodulin sales: the first Remodulin price increase in the U.S. since 2010; a reduction in the price Remodulin is sold to an international distributor in connection with a transfer of additional regulatory and commercial responsibilities to that distributor last year; and a one-time impact of a change in contractual minimum inventory levels with a U.S. distributor.
United Therapeutics also faces generic competition for Remodulin, with four generics makers having reached settlements with the biopharma, and the first generic expected to reach the market this year.
“Even though a generic formulation of Remodulin will eventually enter the market, we continue to believe that Remodulin revenues will increase along with the size of the treated PAH population,” United Therapeutics Chairman and CEO Martine Rothblatt, Ph.D., told analysts August 1 on the company’s quarterly conference call.
“Future growth will be supported by the recognized proven qualities and defining characteristics of branded Remodulin, which include, number one, an established safety profile and supply chain reliability,” Dr. Rothblatt said. We believe that prescribing physicians will continue to recognize and appreciate our established track record and consistent supply chain availability and will, therefore, continue writing prescriptions for branded Remodulin.”
Tyvaso sales last year fell 7.8%, to $372.9 million from $404.6 million—but rebounded 4.6% in January-June 2018, to $200.5 million from $191.6 million in the first half of last year, primarily due to a price hike.