United Therapeutics Abandons Pulmonary Hypertension Program After Failed Phase III Trial
Silver Spring, Maryland-based United Therapeutics announced that its esuberaprost tablet did not meet its primary endpoint in the BEAT Phase III clinical trial in patients with pulmonary arterial hypertension (PAH). The primary endpoint was delayed time to first clinical worsening event.
PAH is one type of a broader disease called pulmonary hypertension, meaning high blood pressure in the lungs. In PAH, the increased pressure is caused by obstruction in the small arteries in the lungs. Symptoms of PAH are similar to those seen in many other common diseases, such as asthma, emphysema or chronic obstructive pulmonary disease (COPD). They include shortness of breath, fatigue, swelling of the feet, legs, belly and neck, chest pain and pounding of the heart.
PAH is marked by progressive scarring of the small blood vessels going to the lungs. The scarring can be caused by a number of different diseases, including scleroderma and lupus, as well as exposure to toxins and drugs like methamphetamine and cocaine, or infections such as HIV and schistosomiasis.
United Therapeutics indicated they will be halting development of esuberaprost. In fact, the press release had very little to say: “United Therapeutics Corporation today announced that the BEAT clinical study of esuberaprost tablets in patients suffering from pulmonary arterial hypertension [PAH] did not meet its primary endpoint of delayed time to first clinical worsening event. Accordingly, United Therapeutics has decided to discontinue further esuberaprost development.”
The company’s primary focus has been on treprostinil in various formulations, oral, inhaled and injectable. However, it’s facing competition from generics. Its injectable Remodulin sales have been decreasing, while its inhaled version, Tyvaso, is growing but is also facing patent competition.
As a result, United has been acquiring rivals and setting up licensing deals. In 2018, it acquired SteadyMed and its pump-based product that combines treprostinil with a pump device. And in September, United inked a license deal with MannKind for a dry powder formulation of the drug.
Jefferies analysts wrote in a note to clients, “Last week, we noted that if Tysuberprost was successful/approved for pulmonary arterial hypertension, net benefits to United’s revenue would be neutral/marginal as Tysuberprost would push out Orenitram/Remodulin use. Though a minimal impact on our PT (~$1/sh NPV for Tysuberprost), we’re cautious on United on declining revenues and lack of pipeline diversification (>90% of revenue from PAH drugs).”
At the company’s fourth-quarter earnings report on February 27, United reported total revenues for the year of $1.628 billion, down 45.7% from $1.725 billion the year before. That was caused mostly by a drop in Remodulin sales of 10.7% from 2017 to 2018 and a 22.9 percent drop in sales of Adcirca in the same period.
Martine Rothblatt, chairman and chief executive officer of United stated at the time, “2018 was a truly transformative year for United Therapeutics. We signed four major agreements to acquire new product candidates, including an in-licensing agreement for ralinepag, representing our largest deal to date. At the same time, we continue to execute against our existing commercial and clinical goals, including the successful readout of our FREEDOM-EV clinical trial, significant progress toward near-term Phase III readouts for our BEAT and DISTINCT studies, and an increase to a record number of patients being treated with our treprostinil therapies.”