Providing Access to Rezdiffra for NASH and the Therapies to Come | AMCP 2024

In a session that discussed the pipeline and a new FDA-approved treatment option for patients with nonalcoholic steatohepatitis (NASH), speakers at the annual meeting of the Academy of Managed Care Pharmacy in New Orleans debated how managed care organizations and health plans can think about coverage for these newer therapies.

Both Donna Cryer, J.D., and Stephanie Spence, Pharm.D., CSP, agreed that there is unmet medical need for patients given the progressive nature of NASH, a severe form of fatty liver disease. NASH is a leading cause of liver-related mortality, especially for those with hypertension and type 2 diabetes. NASH affects between 1.5% and 6.5% of U.S. adults.

Some experts are now calling the disease metabolic dysfunction-associated steatohepatitis, or MASH. But as the speakers pointed out, an ICD 10 code has not yet been established for MASH. The transition to a new code could take some time.

Last month, the FDA approved granted accelerated approved for Rezdiffra (resmetirom), the first drug approved specifically for NASH. It was approved based on a surrogate endpoint. Treatments that have been used for NASH have included lifestyle modification and off-label use of drugs therapies such semaglutide or tirzepatide, drugs that are approved to treat diabetes and weight loss.

Rezdiffra is an oral therapy approved based on data from the ongoing phase 3 MAESTRO-NASH trial. At 52 weeks, Rezdiffra achieved liver histological improvement endpoints: resolution of NASH and reduction of liver fibrosis, two surrogate endpoints. It has shown promise in improving liver scarring and even resolving NASH in some patients after one year.

Stephanie Spence, Pharm.D.

Spence, who is director of specialty pharmacy at CareFirst BlueCross BlueShield, which serves 3.5 million people in Maryland, the District of Columbia and Northern Virginia, said that payers’ prior authorization for Rezdiffra could consider either noninvasive methods or biopsy as way of diagnosing NASH, as well as requiring treatment for comorbid conditions, lifestyle modifications and abstinence from alcohol.

Additionally, Spence mentioned that prescribing would be appropriate through specialty providers. “Primary care doctors are overwhelmed by the prospect of managing such a large population with this condition.”

She also suggested that because of the cost of Rezdiffra, payers should consider value-based contracts with manufacturers. The drug's maker, Madrigal Pharmaceuticals, announced in March after the FDA approved Rezdiffra that it would price drug to cost $47,400 per year.

“There are opportunities, especially as we look at the NASH treatment pipeline, to bring some innovation to the contracts that we have with manufacturers, specifically around outcomes,” said Spence, who suggested that there are still questions about where Rezdiffra fits into NASH treatment. “Are we actually preventing the progression of NASH with these therapies? Or are we just tacking on another therapy?" she asked.

Donna Cryer

During the question and answer part of the session, Donna Cryer, founder and CEO of the patient organization Global Liver Institute, addressed the importance of payers following therapies’ approved labels. For example, she pointed out that Rezdiffra’s label does not require biopsies; instead, patients can be diagnosed with ultrasound imaging or blood tests for biomarkers of liver fibrosis. “I would not want to see a prior authorization require a biopsy since that is not on the label,” Cryer said.

Additionally, Cryer said that the requirement to abstain from alcohol also is not on the label. “The nomenclature of this disease was to create a category separate from alcohol-related liver disease. Certainly, patients should be counseled about the impact of alcohol on the liver. But it’s important to patients to explain to families that this is not about alcohol."

Spence said it is common to require abstention from alcohol for liver diseases because of its impact on the liver. “It’s also in the study design [of Rezdiffra]. There is room for discussion but it is a standard criteria for drugs that are modifying the liver.”

She also said payers should review requiring patients to step through current treatment options, especially with the GLP-1, before being prescribed Rezdiffra

Cryer, however, suggested that requiring steps could make it harder for patients to access needed therapy. “I see this as an opportunity rather than something required. I think this is an opportunity to optimize people’s metabolic profile."

Even with the approval of Rezdiffra, Cryer and Spence agree that a huge need for additional treatments and equitable access remains. Therapies in development are targeting various aspects of the disease, including inflammation, fibrosis and bile acid regulation. They offer the potential to slow or reverse disease progress.

Semaglutide, currently approved as Ozempic to treat diabetes and as Wegovy for weight loss, is in a phase 3 trial for a NASH indication. It is a GLP-1 agonist, which have been used off label for NASH. Other drugs in phase 3 trials include:

• Lanifibranor, an oral PPAR agonist
• Aramchol, an oral SCD1 inhibitor
• Azemiglitizone, an oral thiazolidinedione
• Belapectin, an intraveneous galectin inhibitor
• Efruxifermin, a subcutaneous fibroblast growth factor mimetic