United Therapeutics is throwing its pulmonary arterial hypertension drug esuberaprost on the scrap heap after failing in a phase 3 test.
The press release was short and bitter, one paragraph long and light on details: “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.” And that’s all she wrote.
PAH is a type of high blood pressure that occurs in the pulmonary artery that reaches the lungs from the right-hand side of the heart. Over time, the increased blood pressure can damage the heart. It’s become an area of intense research activity in the biopharma industry with upward of 40 candidates in clinical trials, so it's expected to become a highly competitive category in the coming years.
This also comes at a time when United's franchise in this therapeutic category—focused mainly on treprostinil in oral, inhaled and injectable formats—is facing the threat of competition from generics. Sales of its injectable Remodulin product has been declining, and inhaled version Tyvaso is still growing but is also facing patent challenges.
To try and combat this, the company has been buying up rivals and penning pacts: Last year, the biotech bought up SteadyMed and its neutralizing pump-based threat to its PAH franchise for $216 million, which saw it claim control of its Trevyent combination that pairs treprostinil with a proprietary pump device, and followed that in September with a license deal with MannKind for a dry powder formulation of the drug.
And a few months later, Arena penned an $800 million upfront licensing deal for its other PAH drug, ralinepag.
Analysts at Jefferies said in a note to clients they don’t see this as a major snag, but a limited pipeline focused on PAH and generics are causes for concern: “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 & lack of pipeline diversification (>90% of revenue from PAH drugs).
“In line with guided timing for data in 2Q19, this morning UTHR reports Ph3 BEAT data; Tyvaso + esuberaprost (Tysuberprost) fails to show clinical benefits vs. Tyvaso alone.
“The outcome is in contrast to our prior discussion with a pulmonologist, indicating ~20% clinical benefits of Tysuberprost vs. Tyvaso alone. Ph3 BEAT (Beraprost 314d Added-on to Tyvaso; n=240) assesses efficacy & safety of beraprost 314d/esuberaprost when added to inhaled Tyvaso in PAH. Primary endpoint is time to clinical worsening (death, hospitalization, initiation of SC/IV prostacyclin, disease progression). Tyvaso was approved on 6MWD improvement; esuberaprost (only used in Asia) is an oral prostacyclin analog (similar to Orenitram). Both Tyvaso & esuberaprost are not as potent as Orenitram, with mild/moderate vasodilatory effects; however, their less side effects (vs. Orenitram) would enable to combine the two for better efficacy.”
The more than $5 billion market capped biotech was trading in the red by more than 2% on the news this morning.