On March 26, 2024 the FDA approved sotatercept (brand name of Winrevair), the first new class of medication approved in over a decade. This medication acts by inhibiting signaling in the Activin pathway. A major problem that contributes to PAH for most patients is impaired signaling in the BMPR pathway. You can think of this signaling process as a group of traffic lights. Some of these traffic lights regulate beneficial pathways (BMPR) and others regulate damaging pathways (Activin). In PAH, there are not enough BMPR green lights and there are too few Activin red lights. The net result is that the healthy signals are off and the unhealthy signals are on. Sotatercept, by binding to Activin, turns the damaging pathways off (red lights). As a result of this rebalancing of Activin and BMPR signaling the pulmonary arteries are able to function more normally. Pressure and resistance fall in the pulmonary arteries and patients are able to walk further.
Sotatercept was able to reduce the pulmonary artery pressure and resistance within the pulmonary arteries. In general, the drug was well tolerated but side effects are not uncommon. The most common side effects in the studies with sotatercept were headache, nose bleeds (most were mild), rash and the development of tiny new blood vessels called telangiectasia. Laboratory monitoring prior to each dose for the first 5 doses is very important. This monitors for increased red blood cells and falling platelets (another part of your blood). It is common to see your hemoglobin increase (seen in more than half of patients). Low platelets were less common but were seen in about one quarter of patients.
Importantly, sotatercept has not been studied in pregnancy and as a result, woman who might become pregnant should use effective contraception while on this medication. Women should not breast feed while on sotatercept either. There is no formal safety monitoring program with sotatercept but your blood counts should be monitored regularly and women that are of child-bearing potential must use effective birth control. Sotatercept may also affect male fertility while taking medication. This is felt to be fully reversible after stopping the medication.
Sotatercept is an important new medication for patients with PAH. It powerfully improves exercise capacity, improves pulmonary artery pressure, lowers pulmonary artery resistance and delays clinical worsening.
