EMA has recommended granting a conditional marketing authorisation in the European Union (EU) for Rezdiffra (resmeritom) for the treatment of adults with noncirrhotic metabolic dysfunction-associated steatohepatitis (MASH) with moderate to advanced liver fibrosis, in conjunction with diet and exercise.
MASH is a serious disease where fat deposits accumulate in the liver causing inflammation. MASH is often associated with several cardiovascular (of the heart and blood vessels) and metabolic diseases and, if left untreated, it can lead to cirrhosis (severe and permanent scarring of the liver) and cancer. Currently, there is no authorised treatment for MASH in the EU.
The active substance of Rezdiffra is resmetirom, a liver therapy. Resmetirom stimulates a thyroid hormone receptor (THR‑β) in the liver, reducing the accumulation of fat in the liver, inflammation and liver fibrosis (tissue scarring and thickening).
The opinion of EMA’s human medicines committee (CHMP) is based on data from one pivotal randomised, controlled clinical study. The applicant submitted the results of an interim analysis based on a subset of participants after one year of treatment.
The study included a total of 917 patients with liver fibrosis stage F2 (moderate) and F3 (advanced) at baseline. The participants received 80 mg of resmeritom (306), 100 mg of resmeritom (308) or placebo (303). Results after 12 months showed that 30% of patients in the 100 mg resmeritom and 26% of those in the 80 mg groups achieved MASH resolution with no worsening of fibrosis, compared to 10% in the placebo group. In addition, 29% of patients who received 100 mg of resmeritom and 27% of those who received 80 mg of resmeritom experienced an improvement in liver scarring (fibrosis) and no worsening of MASH, compared to 17% of those who received placebo.
The CHMP considered that the results of the main trial demonstrated the efficacy of Rezdiffra.
The conclusion on the beneficial effects was supported by the submission of two studies conducted in a slightly different population, which partly show similar features as the primary target population. Since the pivotal trial, and one of the two supportive trials, are ongoing, the CHMP has required the applicant to complete these two studies as they are necessary to provide further data regarding the efficacy of Rezdiffra.
The most common side effects in patients treated with Rezdiffra were diarrhoea, nausea and itching.
Rezdiffra is recommended for a conditional marketing authorisation, one of the EU’s regulatory mechanisms to facilitate early access to medicines that fulfil an unmet medical need. This type of approval allows the Agency to recommend a medicine for marketing authorisation with less complete data than normally expected, if the benefit of a medicine’s immediate availability to patients outweighs the risk inherent in the fact that not all the data are yet available.
The opinion adopted by the CHMP is an intermediate step on Rezdiffra’spath to patient access. The opinion will now be sent to the European Commission for the adoption of a decision on an EU-wide marketing authorisation. Once a marketing authorisation has been granted, decisions about price and reimbursement will take place at the level of each Member State, taking into account the potential role/use of this medicine in the context of the national health system of that country.
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