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.
Moving into Second Generation
“On the very same day 21 years ago, we enabled the development of treprostinil into a practical treatment thanks to an invention of the late Al Mann—the discrete, ambulatory, programmable, parenteral infusion pump called the MiniMed 407c. By marrying our molecule and MiniMed's device, Remodulin® was born,” Dr. Rothblatt said in a statement.
She referred to Alfred E. Mann, the philanthropist and entrepreneur who founded and funded MannKind among 17 companies in biopharma and other technologies, before his death in 2016 at age 90.
“As we now move into the second generation of United Therapeutics products, we are proud to once again team with Al Mann's brilliance, this time with his Dreamboat®, Bluhale®, and Cricket® devices for inhalation,” Dr. Rothblatt added. “I believe these revolutionary new inhalation devices will accomplish for Tyvaso what our recently-approved Implantable System for Remodulin, pending RemUnity™ system and recently-acquired Trevyent® product represent for Remodulin—a further step toward a next-generation of treprostinil drug-device systems that enhance options for patients, their families, and their prescribers.”
The FDA on July 31 approved United Therapeutics’ NDA for its Implantable System for Remodulin, developed under a collaboration with Medtronic. RemUnity is a pre-filled, semi-disposable subcutaneous treprostinil pump that United Therapeutics is developing with DEKA Research & Development.
Trevyent is a development-stage drug-device combination treatment for pulmonary arterial hypertension that combines treprostinil with the PatchPump® technology of SteadyMed. In April, United Healthcare agreed to acquire SteadyMed for up to $216 million, in a deal set to close in the third quarter with to treat.
Additionally, MannKind has granted United Therapeutics an option to expand the license to include other active ingredients for treating pulmonary hypertension. For each product it exercises the option to develop, United Therapeutics has agreed to pay MannKind up to $40 million in additional option exercise and development milestone payments, as well as a low double-digit royalty on net sales.
MannKind also agreed to conduct research on behalf of United Therapeutics for products outside the scope of the licensing and collaboration agreement, in return for an immediate $10 million payment.
“We are pleased with this new opportunity to demonstrate the value of our drug and device combination platform for delivering therapeutic products,” MannKind CEO Michael Castagna, Pharm.D., said in a statement. “We believe this collaboration will have the potential to significantly improve the lives of people living with pulmonary arterial hypertension.”
Investors responded to the announcement of the collaboration with United Therapeutics with a stock buying surge that sent MannKind shares zooming 49% from Friday’s close of $1.10, to $1.58 in premarket trading as of 9:28 a.m.