Johnson & Johnson is attempting to change the antidepression market with its ketamine-derivative Spravato despite strict dosing requirements and a steep list price. New data in treating high-risk depression patients could help, but will physicians and payers come around?
Adding Spravato to comprehensive standard-of-care treatment reduced the primary symptoms of major depressive disorder (MDD) with suicidal ideation with intent after 24 hours over a combination of placebo and standard-of-care therapy, according to two phase 3 studies from J&J’s Aspire program.
Patients treated with Spravato showed a significant reduction in symptoms over placebo on the Montgomery-Åsberg Depression Rating Scale, J&J said, hitting the studies’ primary endpoint. In the studies’ secondary endpoint of reducing symptoms over placebo on the revised Clinical Global Impression of Severity of Suicidality, Spravato didn’t show a significant advantage.
The Aspire studies were the first of their kind to treat MDD patients with suicidal intent, primarily because those patients were at abnormally high risk—85% were rated by doctors to be “moderately or severely suicidal”—and had to be hospitalized and on an initial antidepression regimen prior to participation.
According to Carla Canuso, J&J R&D’s senior director of clinical research and the Aspire clinical leader, designing studies that involved already hospitalized patients at high risk presented several methodological challenges that can throw data off track.
“When you design a trial on top of standard of care, it is more difficult to see treatment effect,” she said. “Also, there are not many measures or scale of suicidality that can measure rapid change. So there are very unique methodological challenges contributing to the lack of studies in this area.”
The newest studies could help ease physician concerns around Spravato, a nasal spray that can only be dosed under doctor supervision. One major government payer has already recommended it for only limited use—even after President Donald Trump’s direct endorsement.
In June, the U.S. Department of Veterans Affairs (VA) recommended Spravato for use only after other antidepressants had been tried. That recommendation was a direct rebuttal to Trump endorsing the drug for preferential treatment and even proposing price negotiations between J&J and the VA. But it did largely follow that of the FDA, which approved Spravato only for use in MDD patients who have already failed on two other antidepressants.
Strong data in another small indication don’t add much hope that Spravato will soon break into the mainstream, but David Hough, J&J R&D’s esketamine compound development leader, said the new data and comparable safety figures to older studies should help the drugmaker gain headway with physicians.
“We have a very robust data package that was submitted for major depression,” he said. “Most of the adverse events are associated with dosing—they are transient, and they resolve within an hour or two after dosing. I don’t think that Spravato has significant safety issues.”
Pricing, though, may still be an issue. In early May, the Institute for Clinical and Economic Review (ICER) declined to recommend Spravato for use at its steep list price of $32,400 per year. The U.S. cost watchdog said J&J would need to cut the sticker price between 25% and 52% to be considered cost-effective.
J&J hit back on that recommendation a week later, arguing that Spravato in conjunction with an oral antidepressant could cost $20,000 less per patient than oral therapy plus placebo. But in June, ICER refused to back off its initial recommendation.
Despite those troubles, Hough said J&J had a blossoming relationship with payers and has seen Spravato’s market access growing “faster than we’ve expected.” The drug has 850 certified treatment centers nationwide, he said.
“We’re very happy with that,” he added. “There have been some issues in operationalizing sites, but we have not seen issues (with payers).”