Third Time’s the Charm as Acceleron Drug Shows Early Promise in PAH

Xconomy Boston — 

Sotatercept was one of the first compounds to emerge from the labs of Acceleron Pharma, but it became a forgotten piece of the company’s pipeline. Passed over as a candidate to treat a rare blood disorder and stalled in tests in chronic kidney disease, little was expected of the drug.

The drug’s prospects have changed for the better. Acceleron (NASDAQ: XLRN) late Monday reported positive preliminary data from mid-stage tests of sotatercept in pulmonary arterial hypertension. The Cambridge, MA-based company is now eyeing a Phase 3 study that could lead to FDA approval. Some analysts say the compound has blockbuster potential.

Acceleron’s closing stock price Tuesday was $79.39, up more than 50 percent from Monday’s close.

Pulmonary arterial hypertension is a rare disorder in which high blood pressure develops in the blood vessels that carry blood from the heart to the lungs. Its cause isn’t known but the condition can lead to heart failure and death. Acceleron’s placebo-controlled Phase 2 study enrolled 106 patients. The main goal was to show a statistically significant reduction in pulmonary vascular resistance, a measure of the resistance that the heart must overcome to pump blood to the lungs. The Acceleron drug met that goal, as well as secondary endpoints, such as walking distance for six minutes, which measures how a patient performs under exertion.

Acceleron develops drugs that target TGF-beta, a family of proteins that regulate cellular growth and repair. Sotatercept, an engineered protein, was initially developed as a treatment for anemia in patients who have beta thalassemia, a rare blood disorder. The drug became the centerpiece of a multi-year research collaboration with Celgene. But in 2015, Celegene chose to advance another Acceleron drug, luspatercept, for beta thalassemia.

Celgene and Acceleron opted to try sotatercept as a treatment for anemia in patients who have end-stage renal disease. But in 2016, the partners said that the drug had fallen from the list of priorities. Acceleron looked for other applications for sotatercept. In 2017, under new CEO Habib Dable, Acceleron added pulmonary disorders to its list of top disease targets. The company then announced plans to test sotatercept in PAH. Along the way, Acceleron’s other pipeline candidates led to failure and success. An experimental treatment for a rare form of muscular dystrophy failed in Phase 2 testing. But luspatercept, the drug that Celgene chose to develop over sotatercept for beta thalassemia patients, won FDA approval in November.

On a Monday evening conference call to discuss the sotatercept data, Dable said that developing a new PAH therapy is important because survival rates are poor despite the availability of therapies to treat the condition. The standard of care for PAH is treprostinil, a drug that dilates blood vessels. United Therapeutics (NASDAQ: UTHR) markets treprostinil in three different formulations, and it is the Silver Spring, MD, company’s top seller.

Much of PAH drug research has revolved around finding new ways to administer treprostinil. In 2018, United Therapeutics paid $141 million to acquire SteadyMed, a company developing a disposable pump and skin patch system that administers treprostinil. Liquidia Technologies (NASDAQ: LQDA) used its proprietary nanoparticle technology to develop a dry powder formulation of treprostinil intended to reach deep into a patient’s lungs. On Monday, the Research Triangle Park, NC, company submitted its new drug application to the FDA.

But some companies are trying to offer alternatives to treprostinil. San Diego’s Arena Pharmaceuticals (NASDAQ: ARNA) developed a PAH drug that dilates blood vessels in a different way. In 2018, United Therapeutics paid $800 million up front to acquire rights to that drug.

In the conference call, Dable said Acceleron’s goal is to offer a treatment that supplements currently available PAH therapies. Based on the data so far, SVB Leerink analyst Geoffrey Porges believes the Acceleron drug could perform in the top quartile of PAH drugs, putting its annual revenue potential in the $1.5 billion to $2 billion range within five years of reaching the market. But completing the pivotal study won’t be quick or cheap. Porges says a Phase 3 PAH study typically enrolls 700 to 1,200 patients and takes four to six years.

“We expect the cost of such a study to be considerable, but the R&D investment is likely to have a more compelling return than [Acceleron’s] foray into muscle disease,” Porges wrote.

Acceleron executives said that they plan to meet with regulators to discuss future development of the drug. The company also plans to present more detailed data from the PAH study at a medical conference later this year.

Image by Flickr user University of Liverpool Faculty of Health & Life Sciences via a Creative Commons license