Rezdiffra (resmetirom) er godkjent av FDA i USA for behandling av voksne med ikke-cirrhotic non-alcoholic steatohepatitt (NASH) med moderat til avansert leverarrdannelse (fibrose), for bruk sammen med diett og trening.
Til nå har ikke pasienter med ikke-cirrhotic non-alkoholisk steatohepatitt (NASH) som også har bemerkelsesverdig leverarrdannelse, ikke hatt en medisin som direkte kan behandle deres leverskade. FDA approval of Rezdiffra will, for the first time, provide a behandling option for these patients, in addition to diet and exercise.
NASH is a result of the progression of non-alcoholic fatty leveren sykdom hvor leveren inflammation, over time, can lead to liver scarring and liver dysfunction. NASH is often associated with other health problems such as high blood pressure and type 2 diabetes. By at least one estimate, approximately 6-8 million people in the U.S. have NASH with moderate to advanced liver scarring, with that number expected to increase.
Rezdiffra er en delvis aktivator av en skjoldbruskhormonreseptor; aktivering av denne reseptoren av Rezdiffra i leveren reduserer akkumulering av leverfett.
Sikkerhet og effekt av Rezdiffra
The safety and efficacy of Rezdiffra was evaluated based on an analysis of a surrogate endpoint at month 12 in a 54-month, randomized, double-blind placebo-controlled trial. The surrogate endpoint measured the extent of leveren inflammation and scarring. The sponsor is required to conduct a postapproval study to verify and describe Rezdiffra’s clinical benefit, which will be done through completing the same 54-month study, which is still ongoing. To enroll in the trial, patients needed to have a leveren biopsy showing inflammation due to NASH with moderate or advanced leveren scarring. In the trial, 888 subjects were randomly assigned to receive one of the following: placebo (294 subjects); 80 milligrams of Rezdiffra (298 subjects); or 100 milligrams of Rezdiffra (296 subjects); once daily, in addition to standard care for NASH, which includes counseling for healthy diet and exercise.
At 12 months, liver biopsies showed that a greater proportion of subjects who were treated with Rezdiffra achieved NASH resolution or an improvement in liver scarring as compared with those who received the placebo. A total of 26% to 27% of subjects who received 80 milligrams of Rezdiffra and 24% to 36% of subjects who received 100 milligrams of Rezdiffra experienced NASH resolution and no worsening of liver scarring, compared to 9% to 13% of those who received placebo and counseling on diet and exercise. The range of responses reflects different pathologists’ readings. In addition, a total of 23% of subjects who received 80 milligrams of Rezdiffra and 24% to 28% of subjects who received 100 milligrams of Rezdiffra experienced an improvement in leveren scarring and no worsening of NASH, compared to 13% to 15% of those who received placebo, depending on each pathologist’s readings. Demonstration of these changes in a proportion of patients after just one year of treatment is notable, as the sykdom typically progresses slowly with most patients taking years or even decades to show progression.
Bivirkninger av Rezdiffra
De vanligste bivirkningene av Rezdiffra inkluderte diaré og kvalme. Rezdiffra kommer med visse advarsler og forholdsregler, som legemiddelindusert levertoksisitet og galleblærerelaterte bivirkninger.
Use of Rezdiffra should be avoided in patients with decompensated cirrhosis. Patients should stop using Rezdiffra if they develop signs or symptoms of worsening leveren function while on Rezdiffra treatment.
Legemiddelinteraksjoner av Rezdiffra
Bruk av Rezdiffra samtidig med visse andre legemidler, spesielt statiner for å senke kolesterol, kan føre til potensielt signifikante legemiddelinteraksjoner. Helsepersonell bør henvise til den fullstendige forskrivningsinformasjonen for ytterligere informasjon om disse potensielt signifikante legemiddelinteraksjonene med Rezdiffra, anbefalte dose- og administreringsmodifikasjoner.
De FDA approved Rezdiffra under the accelerated approval pathway, which allows for earlier approval of drugs that treat serious conditions and address an unmet medical need, based on a surrogate or intermediate clinical endpoint that is reasonably likely to predict clinical benefit. The required aforementioned 54-month study, which is ongoing, will assess clinical benefit after 54 months of Rezdiffra treatment.
Rezdiffra fikk betegnelsene Breakthrough Therapy, Fast Track og Priority Review for denne indikasjonen.
De FDA granted the approval of Rezdiffra to Madrigal Pharmaceuticals.
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kilde:
FDA 2024. Nyhetsmelding – FDA godkjenner første behandling for pasienter med arrdannelse i leveren på grunn av fettleversykdom. Lagt ut 14. mars 2024. Tilgjengelig på https://www.fda.gov/news-events/press-announcements/fda-approves-first-treatment-patients-liver-scarring-due-fatty-liver-disease
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