Where pulmonary arterial hypertension treatment is heading

Pulmonary arterial hypertension (PAH) is a rare disease, about 5,000 new US diagnoses a year, mostly women, in which the small arteries of the lungs narrow and stiffen, straining the right side of the heart. For decades treatment only relaxed the blood vessels. Sotatercept, approved in 2024, is the first drug that targets the vessel overgrowth itself, and it now reduces deaths and hospitalizations. More drugs aimed at reversing vessel remodeling are in trials.

• 158studies open or running
• 19phase 3 trials
• 1,420papers published this year
• 40NIH-funded projects

1. Now

   Nov 2026

   Fewer deaths and transplantsHappened 17.4% death, transplant or hospitalization

   In high-risk PAH, sotatercept: 17.4% died, needed a transplant or were hospitalized vs 54.7% on placebo.

   17.4%: died, had a lung transplant or were hospitalized, vs 54.7% with placebo.

   • ZENITH trial

   Earlier use works tooHappened 10.6% clinical worsening

   Starting sotatercept in the first year: clinical worsening 10.6% vs 36.9%.

   10.6%: had clinical worsening, vs 36.9% with placebo.

   • HYPERION trial

   A once-daily prostacyclin pillHappened 55% lower risk of worsening

   Ralinepag cut the risk of worsening by 55%; an FDA filing was planned for late 2026.

   55%: lower risk of clinical worsening.

   • ADVANCE OUTCOMES trial (ralinepag)

   An inhaled anti-remodeling drug fell shortHappened

   Seralutinib missed its prespecified goal in the 390-person PROSERA trial.

   • PROSERA trial (seralutinib)

2. 6 months

   by May 2027

   Ralinepag under FDA reviewPossible

   With a filing planned for the second half of 2026, an FDA decision would follow in 2027.

   • ADVANCE OUTCOMES trial (ralinepag)

3. 12 months

   by Nov 2027

   Long-term sotatercept dataLikely 17.4% events (ZENITH)

   The SOTERIA long-term study (815 people) tracks safety, including bleeding and blood-vessel changes; due December 2028, with interim updates.

   17.4%: died, had a lung transplant or were hospitalized, vs 54.7% with placebo.

   • ZENITH trial
   • SOTERIA

4. 3 years

   by late 2029

   Once-daily inhaled treprostinilPossible

   Insmed's PALM-PAH (344 people) tests treprostinil palmitil once a day; due December 2028.

   • PALM-PAH

   Repurposing tacrolimusLong shot

   TRANSCEND (300 people) tests extended-release tacrolimus, which boosts the BMPR2 pathway; due May 2028.

   • TRANSCEND

5. 5 years

   by late 2031

   Imatinib, reformulatedLong shot

   Inhibikase's IKT-001 (486 people), a gentler form of imatinib, aims to reverse vessel remodeling; due June 2029.

   • IMPROVE-PAH

   Next-generation activin blockersLong shot

   Regeneron's REGN13335 and GSK's HS235 are in phase 2, aiming to improve on sotatercept.

   • REGN13335 trial
   • HS235 trial

The research paths

Borrowed from other conditions

Open to join now

• PAH on background therapy

  IKT-001

  Phase 2/3 · 43 sites

  Locations and eligibility →

• PAH

  Treprostinil palmitil inhalation

  Phase 3 · 39 sites

  Locations and eligibility →

• PAH

  REGN13335

  Phase 2 · 33 sites

  Locations and eligibility →

• PAH

  HS235

  Phase 2 · 7 sites

  Locations and eligibility →

• PAH

  Empagliflozin

  Phase 2 · 3 sites

  Locations and eligibility →

See every recruiting PAH trial →

When the trials finish

Completion dates the trials registered. Results usually follow 3 to 12 months later.

What just happened

Standard treatment today

• Low or intermediate riskTwo oral drugs from the start (an endothelin blocker plus tadalafil or another PDE5 inhibitor).
• Not reaching low riskAdd sotatercept, selexipag, or inhaled treprostinil.
• High riskIV or subcutaneous prostacyclin plus oral drugs; sotatercept; transplant referral.
• End stageLung transplant.

See PAH trials recruiting now →