Rezdiffra (resmetirom) har godkänts av FDA i USA för behandling av vuxna med icke-cirrhotisk alkoholfri steatohepatit (NASH) med måttlig till avancerad leverärrbildning (fibros), för att användas tillsammans med kost och träning.
Hittills har patienter med icke-cirrhotic non-alcoholic steatohepatit (NASH) som också har anmärkningsvärda leverärr inte haft en medicin som direkt kunde åtgärda deras leverskada. FDA: s approval of Rezdiffra will, for the first time, provide a treatment option for these patients, in addition to diet and exercise.
NASH is a result of the progression of non-alcoholic fatty Levern sjukdom var Levern 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 är en partiell aktivator av en sköldkörtelhormonreceptor; aktivering av denna receptor av Rezdiffra i levern minskar fettansamlingen i levern.
Säkerhet och 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 Levern 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 Levern biopsy showing inflammation due to NASH with moderate or advanced Levern 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 Levern 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 sjukdom typically progresses slowly with most patients taking years or even decades to show progression.
Biverkningar av Rezdiffra
De vanligaste biverkningarna av Rezdiffra var diarré och illamående. Rezdiffra kommer med vissa varningar och försiktighetsåtgärder, såsom läkemedelsinducerad levertoxicitet och gallblåserelaterade biverkningar.
Use of Rezdiffra should be avoided in patients with decompensated cirrhosis. Patients should stop using Rezdiffra if they develop signs or symptoms of worsening Levern function while on Rezdiffra treatment.
Läkemedelsinteraktioner av Rezdiffra
Att använda Rezdiffra samtidigt med vissa andra läkemedel, särskilt statiner för att sänka kolesterol, kan resultera i potentiellt signifikanta läkemedelsinteraktioner. Sjukvårdspersonal bör hänvisa till den fullständiga förskrivningsinformationen för ytterligare information om dessa potentiellt signifikanta läkemedelsinteraktioner med Rezdiffra, rekommenderade doserings- och administreringsändringar.
Smakämnen 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 fick beteckningarna Breakthrough Therapy, Fast Track och Priority Review för denna indikation.
Smakämnen FDA granted the approval of Rezdiffra to Madrigal Pharmaceuticals.
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Källa:
FDA 2024. Pressmeddelande – FDA godkänner första behandlingen för patienter med leverärr på grund av fettleversjukdom. Upplagd 14 mars 2024. Tillgänglig på https://www.fda.gov/news-events/press-announcements/fda-approves-first-treatment-patients-liver-scarring-due-fatty-liver-disease
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