Naim Alkhouri, MD: Resmetirom Has Been a “Game Changer” in MASH Since FDA Approval

Since it became the first US Food and Drug Administration (FDA)-approved therapeutic for metabolic dysfunction-associated steatohepatitis (MASH) earlier this year, resmetirom (Rezdiffra) has redefined hepatic care for millions of patients with the progressive liver disease.¹

Prior to the landmark approval, the mainstay of treatment for MASH, formerly known as nonalcoholic steatohepatitis (NASH), was weight loss. Although there is evidence showing that 10% total body weight loss with lifestyle intervention can aid MASH resolution and fibrosis regression, most patients are unable to achieve the amount of weight loss necessary to see these benefits. Even if they do, they typically are not able to maintain it.^1,2

Naim Alkhouri, MD, chief medical officer, chief of transplant hepatology, and director of the Fatty Liver Program at Arizona Liver Health, explained to HCPLive that the growing number of patients who were not successful with the recommended lifestyle interventions highlighted an “urgent unmet need” for an FDA-approved MASH therapeutic. Acknowledging the ways in which GLP-1s have revolutionized obesity management and weight loss, he noted that so far, clinical trial data does not support their impact on fibrosis in patients with MASH. However, he mentioned that phase 3 semaglutide data should eventually clarify the effects of GLP-1s on fibrosis.

“[Resmetirom] has been a historic FDA approval because this is the first medication approved specifically for the indication of MASH and F2 and F3 fibrosis. To have this available to our patients in the clinic has been a game changer,” Alkhouri said, citing low success rates with lifestyle intervention alone and tolerability issues as well as insurance coverage problems with GLP-1s. “To have something that's indicated specifically to treat liver disease is a very nice addition to what we do for these patients.”

Looking at the patient perspective, Alkhouri explained how many of his patients have had type 2 diabetes for more than a decade and have spent much of this time trying to lose weight with little success. Now, he says these patients are “relieved” to know that there is a therapeutic to help.

Alkhouri was careful to note that resmetirom’s FDA approval was conditional, with continued approval contingent upon verification and description of clinical benefit in ongoing confirmatory trials. Following the accelerated approval, Madrigal Pharmaceuticals noted plans to meet this requirement by completing the ongoing 54-month, randomized, double-blind placebo-controlled MAESTRO-NASH trial measuring the extent of liver inflammation and scarring. A second ongoing outcomes trial is also evaluating progression to liver decompensation events in patients with well-compensated NASH cirrhosis treated with resmetirom versus placebo.1

For all of the good that resmetirom has done for patients with MASH and moderate to advanced fibrosis thus far, Alkhouri called attention to ongoing unmet needs in the hepatic landscape. Specifically, he referenced the fact that there is still no indication for patients with MASH and cirrhosis, ongoing uncertainties about the safety and efficacy of GLP-1s in MASH, selecting patients without the need for biopsy and continuing to monitor them with noninvasive tests, and eventually achieving a “MASH cure” by targeting upstream and preventing progression to F2 and F3.

“More to come on this, but I think to have this medicine available to us in clinic today is a big deal,” Alkhouri concluded.

References:

1. Brooks, A. Resmetirom (Rezdiffra) Receives Historic FDA Approval for Noncirrhotic NASH. HCPLive. March 14, 2024. Accessed June 3, 2024. https://www.hcplive.com/view/resmetirom-rezdiffra-receives-historic-fda-approval-for-noncirrhotic-nash
2. Brooks, A. Stephen Harrison, MD: The Role of Weight Loss, Resmetirom in NASH Management. HCPLive. March 18, 2024. Accessed June 3, 2024. https://www.hcplive.com/view/stephen-harrison-md-weight-loss-resmetirom-nash-management
3. Resmetirom (Rezdiffra) Now Available in US Pharmacies, Marks Turning Point in NASH Management. HCPLive. April 9, 2024. Accessed June 3, 2024. https://www.hcplive.com/view/resmetirom-rezdiffra-now-available-in-the-us-pharmacies-marks-turning-point-in-nash-management