Goldman Sachs coined 2019 as the “Year of NASH.” They weren’t wrong, but it wasn’t all positive . . . this year, NASH is expected to be the leading cause of liver transplants, and by 2030, prevalence of NASH is expected to increase by 63%. As we grow from the “Year of NASH” to the “Decade of NASH” let’s quickly recap some of the noteworthy trial results of 2019: Gilead’s STELLAR Phase 3 trial
and Cirius’ Phase 2 trials missed their primary endpoints, while CymaBay’s Seladelpar appeared to worsen NASH in patients.
As sponsors rush to become the first to get their NASH treatments approved and into market, we have reviewed the most promising headlines we saw during the “Year of NASH”:
Intercept Pharmaceuticals Met Primary Endpoints with OCA
Of the compounds in Phase 3 trials, only one is expected to launch in 2020, with an FDA advisory panel scheduled for June 2020. Ocaliva® (obeticholic acid; OCA), developed by Intercept Pharmaceuticals, while already approved for primary biliary cholangitis (PBC), showed mixed results in fibrosis (Stages F2 and F3) It only met one of its primary endpoints at the 18-month interim analysis of the REGENERATE study. The actual reduction in NASH stage vs. placebo, however, was disappointing to investors and HCPs with less than a quarter of patients on the highest dose meeting the primary endpoint.
Genfit’s RESOLVE-IT Continues to Move Forward
Elafibranor, under clinical investigation by Genfit in the RESOLVE-IT Phase 3 trial, is promising based on the mechanism of action (PPAR α/δ agonist) and Phase 2 data, which showed improvement in lipid profiles, insulin sensitivity and glucose metabolism, and anti-inflammatory properties. Recent DSMB reviews of elafibranor safety and tolerability data have supported continuation of the ongoing Phase 3 RESOLVE-IT study without any modification, adding to the excitement about this treatment.
Madrigal Pharmaceuticals Shows Promise with Resmetirom
Madrigal Pharmaceuticals may become the new NASH frontrunner with Resmetirom based on initial Phase 2 data from MGL-3196. Their 36-week study met its primary endpoint with a reduction in hepatic fat measured by MRI-PDFF at week 12 and sustained fat reduction at week 36. Results were confirmed by biopsy and correlated with secondary fibrosis biomarkers and liver enzymes.
Looking Ahead
As clinical trials for NASH continue full steam ahead in 2020 with more than 100 compounds at some stage of development (preclinical through Phase 3), sponsors will need to enroll at least 10,000 patients. With a typical NASH screen-fail rate nearing 80%, this will require up to 50,000 screened patients. As enrollment slows, costs increase, and Ocaliva® is approved, patients will become increasingly harder to find, making patient recruitment efforts even more important to the success of clinical trials.
Learn More
Learn more about recruiting patients for NASH trials at the upcoming NASH Summit in Boston, May 4-7.
To read more about how to successfully develop motivating NASH materials, click here. To learn about focused site support for NASH trails, click here.
References
(2019, May 21). Increasing Awareness Of NAFLD/NASH– 2019 Is “The Year Of Nash” According To Goldman Sachs. https://www.bioclinica.com/blog/increasing-awareness-nafldnash-%E2%80%93-2019-%E2%80%9C-year-nash%E2%80%9D-according-goldman-sachs
Younossi, Z. (2019, April 14). Positive Results from REGENERATE: A Phase 3 International, Randomized, Placebo-Controlled Study Evaluating Obeticholic Acid Treatment for NASH. http://www.natap.org/2019/EASL/EASL_09.htm
Elafibranor in NASH. https://www.genfit.com/pipeline/elafibranor/
(2019, November 11). Madrigal Pharmaceuticals Announces Publication in The Lancet of Positive Phase 2 Results for Resmetirom (MGL-3196) for the Treatment of Non-alcoholic Steatohepatitis (NASH). https://www.madrigalpharma.com/wp-content/uploads/2019/11/Lancet_Madrigal-Pharmaceuticals-Announces-Publication-of-Positive-Phase-2-Results-for-resmetirom.FINAL_11_11_2019.pdf
