With Merck's key PAH approval on tap, Johnson & Johnson wins nod for combo tablet

With the FDA expected this week to approve a first-in-class treatment from Merck for pulmonary arterial hypertension (PAH), Johnson & Johnson has beaten its New Jersey rival to the punch with a nod from the U.S. regulator for its newest PAH treatment.

The FDA has signed off on Opsynvi, a tablet that combines J&J’s Opsumit (macitanten) and United Therapeutics' Adcirca (tadalafil), which are commonly prescribed together to treat the condition. PAH is a rare, rapidly progressing disease in which the blood vessels narrow in the lungs, increasing blood pressure and leading to heart failure.

Opsynvi becomes the only once-daily, single-tablet combination therapy for PAH. It can be used by newly diagnosed patients who are treatment-naïve. It can also be used by those who are already on Opsumit, an endothelin receptor antagonist (ERA), or on Adcirca, a phosphodiesterase 5 (PDE5) inhibitor, or on both.

Tadalafil has been on the market for 20 years as Eli Lilly’s erectile dysfunction drug Cialis, and is now subject to generic competition. Opsumit was approved in 2013 for PAH. For those with the condition who take both drugs, macitentan reduces the risk of clinical worsening events and hospitalization, while tadalafil improves exercise ability.

“People with PAH often live with the burden of taking many pills each day, which can pose challenges,” James List, M.D., Ph.D., who oversees a portfolio of programs at J&J that includes pulmonary hypertension, said in a release. “(Opsynvi) has the potential to optimize disease management and fulfill a significant unmet need in supporting recently updated treatment guidelines that call for initial or early combination treatment.”

The FDA nod comes ahead of Tuesday’s highly anticipated decision date for Merck’s sotatercept, which is lined up to become the first disease-modifying treatment for PAH. The drugs are not expected to be in competition because sotatercept is designed as an add-on therapy to current treatments such as Opsumit and Adcirca, which help patients deal with the symptoms of PAH.

FDA endorsement of Opsynvi was based on results from the A DUE study that showed it significantly improved blood flow through pulmonary vessels versus Opsumit or Adcirca as monotherapies. The trial, which included 187 patients in 19 countries, showed that Opsynvi provided a 29% reduction in pulmonary vascular resistance (PVR) compared with those on Opsumit alone and a 28% reduction over those on Adcirca.

The trial enrolled PAH patients with Class II and Class III levels of PAH. Those in Class II have no symptoms at rest but are uncomfortable and short of breath during normal activities such as climbing a flight of stairs. The activities of Class III patients are greatly limited by shortness of breath, fatigue or near fainting when attempting things such as household chores.

Roughly 40,000 people in the U.S. have PAH, with 500 to 1,000 newly diagnosed each year. PAH strikes more women than men and most are in middle age, killing nearly half within five years of diagnosis. The condition begins as a more common disorder, pulmonary hypertension (PH), then can progress into PAH.  

J&J dominates the PAH market, with Opsumit producing $2 billion in sales last year, and the newer Uptravi (selexipag), a prostacyclin receptor (IP) agonist, generating revenue of $1.6 billion. J&J picked up both drugs in its $30 billion acquisition of Acctelion in 2017. While the therapies dilate the blood vessels to alleviate symptoms, they do little to ameliorate the disease.

Last year, J&J filed patent infringement lawsuits against Sun Pharma, Alembic Pharma, Apotex and MSN Laboratories, all of which have filed FDA applications for their generic versions of Opsumit.

Also last year, J&J pulled the plug on a trial testing a higher-dose version of Opsumit to treat the pulmonary hypertension condition chronic thromboembolic pulmonary hypertension (CTEPH). The decision came after an independent data monitoring committee concluded that the trial would not be successful.