PAH Drug Development Is Ramping Up: 3 Things To Know

In the latest sign that drug development for pulmonary arterial hypertension (PAH) is gathering momentum, the San Diego-based biopharmaceutical firm Gossamer Bio announced a deal earlier this month with the Italian drugmaker Chiesi Group to partner on the development and commercialization of seralutinib, a potential treatment for PAH and pulmonary hypertension associated with interstitial lung disease (PH-ILD).

Gossamer’s chief executive, Faheem Hasnain, said in a new release that the deal will allow his company to “meaningfully deepen and rapidly accelerate” their investment in seralutinib.

Under the terms of the deal, Gossamer will receive a $160 million development reimbursement and up to $146 million if certain regulatory milestones are met, plus up to $180 million if sales milestones are achieved. The two companies will split commercialization costs. Gossamer will lead commercialization efforts for PAH and PH-ILD in the United States, but Chiesi will lead commercialization efforts for other indications, and have the exclusive right to commercialize the drug outside the US, the companies said.

The deal is the latest in a spate of news about PAH drug development.

Winrevair approved

The deal between Gossamer and Chiesi is far from the only news related to PAH therapy. Merck’s Winrevair (sotatercept-csrk) was approved by the FDA in March for the treatment of PAH in adults with World Health Organization Group 1 disease. The approval made it the first activin signaling inhibitor available for the treatment of PAH.

At the time of the approval, Aaron Waxman, MD, PhD, of Brigham and Women’s Hospital, said “Sotatercept added to background therapy has the potential to become a new standard of care option for patients with pulmonary arterial hypertension.”

Waxman was an investigator on the phase 3 trial of sotatercept.

That same month, the FDA gave its nod to the combination PAH therapy Opsynvi, a single-tablet combination of the endothelin receptor antagonist macitentan and the phosphodiesterase 5 inhibitor tadalafil.

Additionally, the drugmaker Inhibikase Therapeutics offered an update on its development of IkT-001Pro as a treatment for PAH. That drug has as its active ingredient imatinib (Gleevec), a targeted cancer therapy. The company said the FDA supported its phase 2/3 trial design, but also requested a pre-clinical cell-culture based study of the therapy. The company added that it is looking for strategic partners to advance its development of the therapy for a PAH indication.

Gossamer-Chiesi deal may boost R & D

Seralutinib is an inhaled platelet-derived growth factor receptor alpha/beta (PDGFRα/β), colony stimulating factor 1 receptor (CSF1R), and mast/stem cell growth factor receptor kit (c-KIT) inhibitor. Gossamer launched the phase 3 PROSERA Study last year to test the therapy in patients with PAH. Prior to that, the phase 2 TORREY Study found the treatment significantly reduced pulmonary vascular resistance in 44 adults with PAH.

With the Chiesi partnership, Gossamer said the two companies plan to launch a global phase 3 registrational study of PH-ILD next year. They will also evaluate the therapy for the treatment of other conditions for which there is a significant unmet need.

Drugs for PH-ILD another strong potential market

In a conference call announcing the Gossamer-Chiesi deal, Gossamer’s chief financial and chief operating officer, Bryan Giraudo, said before the Chiesi deal, Gossamer had been discussing the possibility of a proof-of-concept phase 2 trial for seralutinib in patients with PH-ILD.

“[B]ut because of this partnership we are now able to move seralutinib directly into a registrational global phase 3 clinical trial for the treatment of PH-ILD,” he said in the call.

That trial could start sometime in the middle part of 2025, he said, meaning the drug could be on the market for PH-ILD “years earlier” than previously planned. That’s a big deal for the company, he said, in part because he said the market for that indication is currently wide open.

“Understanding the evolving nature of the competitive nature in pulmonary hypertension, we are striking while the iron is hot,” he said. “...Suffice it to say, we believe that PH-ILD is a multibillion dollar opportunity for seralutinib due to the lack of approved drugs, its population size, and considerable unmet need.”

The company noted that the median five-year overall survival rate for people with PH-ILD is just 23%. Nonetheless, there is only one approved therapy in the US for PH-ILD, and none approved outside the US.