For Johnson & Johnson’s depression nasal spray Spravato, pricing has not only attracted criticism in the U.S. but also hurt its effort to win backing from England's influential cost watchdogs. The National Institute for Health and Care Excellence (NICE) rejected coverage of the new ketamine-like drug, also known as esketamine, citing cost concerns and a lack of clinical evidence comparing it to existing oral antidepressants. A nasal spray, Spravato must be administered under a healthcare provider's supervision. “Introduction of esketamine into clinical practice in the [National Health Service] will be complex because the structure and delivery of services would need to be changed,” Meindert Boysen, director of the center for health technology evaluation at NICE, said in a statement. “Estimates of the costs of providing the clinical service for esketamine were highly uncertain, as are the costs of repeated courses of the drug.” Spravato won an EU nod in December as an add-on therapy alongside an oral drug to treat adults whose depression hasn’t responded to at least two different medications. Even though patients can dose themselves, a healthcare professional needs to monitor their reactions to minimize safety risks. According to a NICE draft guidance (PDF), J&J’s own economic model suggests an average price of about £10,550 ($13,720) per course for Spravato before any discount. But a drug’s price is always evaluated against its clinical benefit in NICE’s cost-effectiveness assessment. For Spravato, NICE regulators think J&J needs to provide more data. RELATED: J&J, in rebuttal to pricing criticism, says antidepressant Spravato is cost-effective Billed as an antidepressant that offers a new mechanism of action in 30 years, Spravato is an NMDA glutamate receptor antagonist. In five phase 3 trials, Spravato added to an oral antidepressant proved more effective at reducing depressive symptoms compared with the oral drug paired with a placebo. However, NICE reviewers argue Spravato doesn’t have data versus “all relevant comparators.” For example, it’s unknown how the therapy fares against electroconvulsive treatment, combinations of oral antidepressants or oral antidepressants augmented with lithium or antipsychotic meds, which are included in NICE's recommendations for treating depression. In addition, the agency highlighted uncertainty about the effect of stopping Spravato. “It is unclear if any improvements in symptoms will be maintained after a course of treatment and whether this will improve someone’s quality of life,” the agency's draft guidance says. As a result, the costs of repeated treatment are unknown, as are the costs of additional clinic visits. J&J’s clearly disappointed with NICE’s decision; Jennifer Lee, director of health economics, market access and reimbursement and advocacy at Janssen-Cilag, said it “may potentially deny patients living with treatment-resistant major depressive disorder access to a much-needed new treatment option.” “It is evident from this initial draft guidance that current NICE technology appraisal processes are not fit for purpose in terms of evaluating innovative technologies for complex mental health conditions, an area that is already under-researched and underfunded,” she added. RELATED: J&J scores Spravato trial win in high-risk depression. Will doctors and payers buy in? A rejection from NICE isn’t the first time Spravato has hit a cost-effectiveness nerve. U.S. drug cost watchdogs at the Institute for Clinical and Economic Review previously lambasted J&J for “overpricing” Spravato, though the company later hit back with its own model to justify the price. It’s not the end of road for the drug at NICE, though. The draft guidance is now open for comment until Feb. 18, and the agency expects to convene a second appraisal committee meeting afterward. Meanwhile, J&J recently filed for U.S. and EU approvals to expand Spravato’s use into patients with major depressive disorder who have current suicidal thinking.