Macitentan

Based on a new analysis of human pregnancy data compiled from the use of endothelin receptor antagonist (ERA) medicines for two decades, FDA has determined that risk evaluation and mitigation strategy (REMS) requirements related to embryofetal toxicity (EFT) risk are no longer necessary to ensure the benefits of ERA medicines outweigh those risks. The Agency’s current assessment is that labeling alone is adequate to communicate the risk, and labeling will continue to inform health care professionals and patients of the risk. In April 2025, FDA eliminated the REMS for the following ERA medicines: Eliminated REMS ERA Medicine Ambrisentan Shared System REMS Letairis and generics (ambrisentan) Macitentan-Containing Products Shared System REMS Opsumit and generics (macitentan) Opsynvi (macitentan and tadalafil) Tryvio REMS Tryvio (aprocitentan) Elimination of these REMS means: Health care professionals can prescribe and dispense ambrisentan, macitentan-containing products, and Tryvio (aprocitentan) without enrolling or participating in a REMS. Patients can receive ambrisentan and macitentan-containing products without enrolling in a REMS; the Tryvio REMS did not require patient enrollment. Pharmacies and health care facilities can dispense ambrisentan, macitentan-containing products, and Tryvio (aprocitentan) without enrolling or participating in a REMS. Additionally, FDA notified manufacturers of the following ERA medicines that they must modify the REMS to remove requirements related to EFT risk. FDA will notify prescribers, pharmacies, and patients when these REMS have been modified in fall 2025. REMS requirements related to hepatotoxicity (liver damage) risk for these ERA medicines will remain in effect. Modified REMS ERA Medicine Bosentan Shared System REMS Tracleer and generics (bosentan) Filspari REMS Filspari (sparsentan) ERA prescribing information and EFT risk Information about EFT and mitigation of this risk will remain in the prescribing information for ERA medicines. Use of ERA medicines is contraindicated in pregnancy. Based on data from animal EFT studies, pregnant patients should not use ERA medicines as they may cause fetal harm. Patients who can get pregnant should ensure they are not pregnant prior to starting treatment with an ERA medicine and use effective contraception while taking an ERA medicine. Prescribers should exclude pregnancy prior to treatment initiation and advise patients who can get pregnant of the potential risk to a fetus and of the need to use effective contraception while they are treated with an ERA medicine. Basis for removing ERA REMS requirements for EFT risk FDA regularly assesses the benefits and risks of REMS programs and may eliminate a REMS or remove certain components of a REMS if, after review of REMS assessments or other information, we determine that the extra measures in a REMS are no longer necessary to ensure a medication’s benefits outweigh its risks. FDA’s ERA REMS requirements for EFT risk were based on findings from animal studies. Over time, the Agency monitored clinical outcomes reported in patients exposed to ERA medicines during pregnancy and observed that these data did not show a pattern of congenital malformations consistent with what was observed in animal EFT studies. Given the Agency's new analysis and understanding of clinical risk, FDA determined that labeling for all ERA medicines is sufficient to provide information about EFT risk and its mitigation. Whom do I contact? Prescribers, pharmacies, and patients may contact the FDA at (855) 543-3784 or (301) 796-3400, or by email at druginfo@fda.hhs.gov with questions. Adverse events, medication errors, or quality problems experienced with ERA medicines should be reported to FDA's MedWatch Adverse Event Reporting program . FDA’s top priority is patient safety, and we will continue to monitor the safety of these drugs. Legal Disclaimer: EIN Presswire provides this news content "as is" without warranty of any kind. We do not accept any responsibility or liability for the accuracy, content, images, videos, licenses, completeness, legality, or reliability of the information contained in this article. If you have any complaints or copyright issues related to this article, kindly contact the author above.

Merck’s Winrevair excelled in a phase 3 trial of high-risk pulmonary arterial hypertension patients, reducing the risk of death, lung transplantation and hospitalization by 76% versus placebo. The interim result was conclusive enough that Merck halted the trial and another Winrevair phase 3 study of newly diagnosed patients. The interim results of a phase 3 trial of Merck’s pulmonary arterial hypertension (PAH) treatment Winrevair were so conclusive that the company not only halted the study for efficacy, but did the same two months later in another trial of the first-in-class activin signaling inhibitor.Merck has revealed data from the study, providing further evidence of the value of Winrevair, which has been approved in more than 40 countries, including in the U.S. a year ago. The Zenith trial included 172 patients at the highest risk of mortality—those in the World Health Organization Functional Class (FC) III or IV—and achieved its primary endpoint of time to clinical worsening to first morbidity or mortality event.Winrevair added to maximum background therapy reduced the risk of all-cause death, lung transplantation and hospitalization by 76% versus placebo plus maximum background therapy. Patients received a subcutaneous dose of Winrevair every three weeks, and the median follow-up with patients was 10.6 months.“I’ve been doing clinical research for almost 30 years and have never seen a study with a hard-outcome endpoint with this effect size,” Joerg Koglin, M.D., Merck’s head of general medicine, global clinical development, said in an interview with Fierce Pharma. “There has not been a PH study that used an endpoint based on death, hospitalization or lung transplant. It also is the first PH phase 3 study that was ever stopped early. I think that puts the effect size in perspective.”Merck presented the Zenith data at the American College of Cardiology Annual Scientific Session & Expo on March 31 in Chicago. Results also were reported in The New England Journal of Medicine.   For Winrevair patients in Zenith, 17% had one or more major morbidity or mortality event, compared to 55% of patients in placebo arm. Of the 86 patients on each side of the study, there were seven deaths in the Winrevair arm (8%) compared with 13 in the placebo arm (15%).One patient on Winrevair had a lung transplant (1%) while six on placebo (7%) needed the procedure. PAH hospitalizations occurred in eight patients on Winrevair (9%) compared to 43 patients (50%) on placebo.Koglin said that Merck pursued an ambitious endpoint—not undertaken in other trials—because Winrevair is the first medicine that targets the underlying cause of PAH, while other therapies for the disorder ameliorate its symptoms.One secondary endpoint where the study came up short was overall survival. While there were nearly twice as many deaths (13) on the placebo side of the trial compared to Winrevair (seven), the difference did not achieve statistical significance.“When you run an interim analysis, you are using a much higher statistical bar because the interim analysis is much smaller,” Koglin explained.Setting up Winrevair for its FDA approval was the Stellar phase 3 study, which used exercise capacity as its primary endpoint. Patients who were on Winrevair added to standard of care improved their distance in a six-minute walk test by an average of 41 meters.While the Stellar trial included longtime PAH patients at a lower risk of mortality (from the FC II and III classes), Merck’s phase 3 Hyperion study focused on those who were diagnosed with the disorder within the previous 12 months.Hyperion was halted two months ago after a review of the interim results of the Zenith study. Merck’s chief medical officer Eliav Barr, M.D., said in a release that it would be unethical to give patients placebo when the superiority of Winrevair was clearly established.All 300 patients in both the Zenith and Hyperion trials were offered to receive Winrevair through the Soteria open-label extension study. Koglin said the company will reveal Hyperion data later this year.PAH is a rare, rapidly progressing disease in which the blood vessels in the lungs become thickened and narrower due to a dangerous buildup of cells, leading to shortness of breath and difficulty in the heart’s ability to pump blood to the lungs, which increases blood pressure and can lead to heart failure. Winrevair works by rebalancing the cell signaling.Roughly 40,000 people in the U.S. have the disorder. 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. Winrevair was initially developed by Acceleron and Celgene. Merck gained its rights with its $11.5 billion buyout of Acceleron in 2021. The company makes royalty payments on sales of Winrevair to Bristol Myers Squibb, which bought out Celgene in 2019.Merck reported 2024 sales of Winrevair at $419 million, with nearly half of that, $200 million, coming in the fourth quarter alone.Analysts from Citi said that the full dataset from Zenith shows the "paradigm shifting impact of Winrevair in PAH. ” Citi has boosted its 2025 sales projection of Winrevair from $1.3 billion to $1.5 billion, while lifting its 2030 peak sales estimate from $5.7 billion to $6.1 billion. Johnson & Johnson controls the PAH market with endothelin receptor agonist Opsumit and prostacyclin receptor Uptravi, which were approved in 2013 and 2015, respectively, and garnered combined sales of $4 billion in 2024.Last year, the FDA approved a combination tablet Opsynvi, which combines Opsumit and United Therapeutics’ Adcirca, which are often prescribed together for PAH. These therapies dilate the blood vessels to alleviate PAH symptoms.