Opsynvi experts: Single combo tablet likely to be easier for patients

Approved J&J treatment for PAH now available in US via specialty pharmacy

Lindsey Shapiro, PhD avatar

by Lindsey Shapiro, PhD |

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As of April 15, Opsynvi (macitentan and tadalafil) — the first single-tablet treatment combination approved by the U.S. Food and Drug Administration (FDA) for pulmonary arterial hypertension (PAH) — is available to eligible patients in the U.S. through a specialty pharmacy network.

With its launch, PAH patients who were separately using both of Opsynvi’s main ingredients — macitentan and tadalafil — can now achieve the same clinical results without the burden of taking several pills. The medication also can be used by patients who were only on one type of these medications, or were treatment-naïve, but whose doctors think they’ll benefit from the combination.

Two Opsynvi experts, one an investigator in the Phase 3 A DUE clinical trial that backed the therapy’s approval, said in a written Q&A with Pulmonary Hypertension News that taking just one medication likely will be much more convenient for individuals with PAH moving forward.

“Patients … will only need to remember to take a single [tablet] vs. taking three tablets,” said Kelly Chin, MD, the trial investigator, who also serves as the director of the pulmonary hypertension program at UT Southwestern Medical Center, in Dallas.

“It’s a small thing, but many patients are also on multiple other medications and it really does add up,” Chin said.

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Macitentan, sold as Opsumit by Opsynvi’s developer Janssen Pharmaceuticals — now Johnson & Johnson Innovative Medicine (J & J) — is an endothelin receptor antagonist, or ERA. Tadalafil, meanwhile, is a phosphodiesterase inhibitor (PDE5i) that’s marketed in the U.S. under the brand name Adcirca by United Therapeutics.

Both classes of medicines work in different ways to relax and widen blood vessels to make blood flow easier. Guidelines recommend they be used in combination for treating PAH, and macitentan plus tadalafil are commonly prescribed together as a first-line approach.

“Historically, this required patients to take multiple pills because no single-tablet combination therapy targeting two or more pathways was available,” said Sean Studer, MD, vice president of medical affairs at J&J Innovative Medicine, in the written Q&A.

“The introduction of a single tablet combining both is promising for clinicians treating patients as it may help bridge the gap between clinical guidelines and everyday clinical practice,” Studer added.

According to Studer, the company is pricing Opsynvi similarly to Opsumit alone.

As such, insured patients “will pay no more for Opsynvi than they would for macitentan … foregoing any [out-of-pocket] cost of a separate PDE5 inhibitor prescription,” Studer said.

For patients and their doctors who are looking for support as they navigate either a treatment start or a switch to Opsynvi, Studer said the company has a “a variety of programs” available. These include initiatives “to help make it easier for them to afford their medicines,” Studer said.

On Janssen’s CarePath website, a voucher program is described wherein patients prescribed Opsynvi can receive a free trial of the medication. After that, patients can decide with their healthcare provider whether to continue treatment.

The program is available regardless of whether patients have commercial insurance, government insurance, or are uninsured.

The website also includes other resources, including information about getting started on Opsynvi and navigating healthcare coverage.

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Leading to Opsynvi’s approval, the A DUE trial (NCT03904693) demonstrated the benefits of the combination treatment compared with either macitentan or tadalafil alone. The trial had enrolled 187 PAH patients in World Health Organization (WHO) functional class 2 or 3.

In particular, the combination tablets led to significant reductions in pulmonary vascular resistance — known as PVR, it’s a measure of resistance to blood flow — compared with either treatment on its own, regardless of whether patients had been treatment-naïve or on monotherapy before the trial.

“When PVR is very elevated, as occurs in PAH, lowering it is critically important because failing to do so leads to heart failure and eventually death,” Chin said.

The scientist noted that there generally is “some correlation” between lowering PVR and data on patient-relevant measures like life quality and exercise capacity. While the A DUE trial wasn’t specifically designed to look at such assessments, the results nonetheless showed that exercise capacity tended to be improved with Opsynvi relative to either monotherapy.

Moreover, quality of life assessments indicated improvements for all groups of trial participants, with no differences between them.

“I suspect this is partially because the study was relatively short, and that you would likely see differences with longer-term use,” Chin said.

No new safety concerns were identified with the combination tablets. According to Chin, the side effects observed in A DUE were largely expected based on the known profile of the two medications. Further, the “discontinuation rate due to adverse events overall was fairly low,” she said.

In addition to backing the benefits of Opsynvi, the trial findings more broadly helped to reinforce “the benefits of macitentan and tadalafil in combination in general in the treatment of PAH,” Chin said.

Taking a single tablet is … about convenience. … You wouldn’t expect to see any difference in efficacy in general unless there was also some improvement in adherence.

Importantly, Chin noted that the combination tablets are not expected to be any more efficacious than taking both tablets separately as long as they’re being used as intended.

“Taking a single tablet is more about convenience,” the investigator said. “You wouldn’t expect to see any difference in efficacy in general unless there was also some improvement in adherence.”

Beyond day-to-day dosing, Studer noted that the combination tablets also might offer convenience when patients head to the pharmacy. Taking just one medication may help to “avoid the complexity of two separate prescriptions,” Studer said.

While tadalafil alone is filled at regular pharmacies, macitentan can only be obtained through a specialty network. Opsynvi will be obtained by mail through a specialty pharmacy network.

Similar regulatory approval for Opsynvi is being sought in the European Union. In Canada, the therapy has been approved since 2021 as a substitute for patients who were already taking both classes of medications separately. Studer noted that there are currently no plans to seek a label expansion for treatment-naïve or monotherapy-treated patients in that country.

J & J touts that Opsynvi has now joined its portfolio of PAH therapies that target all three guideline-recommended PAH treatment pathways — nitric oxide, endothelin, and prostacyclin.

“We take pride in our long-standing commitment to PAH [patients],” Studer said, noting that the company is looking forward to results from ongoing trials of Opsumit and Uptravi (selexipag) in pediatric PAH patients, as well as a dose-comparing study of Opsumit’s macitentan in adults.

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