NGM Bio Presents Positive Phase 2b Results from the ALPINE 4 Trial of Aldafermin in Patients with Compensated Cirrhosis (F4) Due to NASH at AASLD The Liver Meeting®
--As previously reported, the ALPINE 4 study met its primary endpoint, with aldafermin 3 mg demonstrating a statistically significant reduction in Enhanced Liver Fibrosis (ELF) score compared to placebo after 48 weeks of treatment--
--ELF, an FDA-approved non-invasive blood test, can be used to predict liver-related events in patients with nonalcoholic steatohepatitis (NASH) and compensated cirrhosis--
--Dose-dependent improvements reported across histologic and multiple non-invasive secondary endpoints in ALPINE 4--
--In the trial, aldafermin treatment up to one year was generally well tolerated with no treatment-related serious adverse events--
SOUTH SAN FRANCISCO, Calif., Nov. 13, 2023 (GLOBE NEWSWIRE) -- NGM Biopharmaceuticals, Inc. (NGM Bio) (Nasdaq: NGM), a biotechnology company focused on discovering and developing transformative therapeutics for patients, today shared positive, comprehensive results from its Phase 2b ALPINE 4 trial of aldafermin, an engineered FGF19 analog product candidate, in patients with compensated cirrhosis (liver fibrosis stage 4 or F4) due to NASH in an oral plenary presentation at the American Association for the Study of Liver Diseases (AASLD) The Liver Meeting®.
The presentation titled “Positive Results from the ALPINE 4 Study: a Randomized, Double-blind, Placebo-controlled, Multicenter, Phase 2b Trial Evaluating Multiple Doses of the FGF19 Analogue Aldafermin in Patients with Compensated Cirrhosis Due to Nonalcoholic Steatohepatitis,” is available to conference attendees for the duration of AASLD The Liver Meeting and will be archived on the ‘Publications’ page of NGM Bio’s website here following the meeting. The ALPINE 4 data shared at AASLD The Liver Meeting follow positive topline results on the primary endpoint reported by NGM Bio in May 2023.
Mary E. Rinella, M.D., Professor of Medicine and Director, Metabolic and Steatotic Liver Disease Program at the University of Chicago Pritzker School of Medicine, who gave the oral presentation, commented, “We are pleased to see that the ALPINE 4 study is the first Phase 2b in NASH cirrhosis to reach its primary endpoint. In addition to demonstrating statistically significant reductions in ELF score, the trial primary endpoint, aldafermin also signaled dose-dependent improvements in liver fibrosis and multiple non-invasive secondary endpoints. Compensated cirrhosis due to NASH is a notoriously difficult-to-treat disease with no approved treatment options. It’s very encouraging to see multiple key clinical measurements moving in the right direction in the ALPINE 4 study, a promising achievement in the quest to bring forward safe, effective therapeutics for patients suffering with F4 NASH.”
“We are excited to share the comprehensive positive data set from the ALPINE 4 study with the hepatology community at AASLD. It’s gratifying to see the potential impact aldafermin is having on NASH progression and liver health in patients with F4 NASH. This Phase 2b data set furthers our belief in aldafermin’s therapeutic potential,” said Hsiao D. Lieu, M.D., Chief Medical Officer at NGM Bio.
The ALPINE 4 trial evaluated the efficacy, safety and tolerability of 1 mg and 3 mg doses of aldafermin compared to placebo in 160 patients with compensated cirrhosis (F4) due to NASH. (A 0.3 mg aldafermin cohort was part of the original design of the trial and enrolled seven patients prior to being discontinued in favor of enrolling more patients in the 1 mg and 3 mg arms of the trial. Patients in the 0.3 mg arm were primarily evaluated for safety.) The study showed that the primary endpoint was achieved; patients treated with aldafermin 3 mg showed a statistically significant reduction in ELF score compared to the placebo arm after 48 weeks of treatment. ELF is the first and only FDA-approved non-invasive test reflecting NASH prognosis. ELF measures direct markers of liver fibrosis and can be used to predict liver-related events in patients with NASH and compensated cirrhosis.
Although ALPINE 4 was not statistically powered for the secondary endpoint of histological fibrosis improvement of ≥ 1-stage (NASH Clinical Research Network, or CRN, criteria), a dose-dependent trend in fibrosis improvement was observed. Aldafermin demonstrated significant, dose-dependent improvements across all of the study’s non-invasive secondary endpoints, including neoepitope-specific N-terminal propeptide of type III collagen (Pro-C3), alanine aminotransferase (ALT), aspartate aminotransferase (AST), 7alpha-hydroxy-4-cholesten-3-one (C4), bile acids and liver stiffness measurement (LSM) by FibroScan® at week 48. These non-invasive tests are correlated with liver fibrogenesis, liver inflammation and injury, and NASH progression.
Aldafermin was generally well tolerated in the ALPINE 4 study with no treatment-related serious adverse events and a safety and tolerability profile generally consistent with prior trials of aldafermin, including higher levels of gastrointestinal events in patients treated with aldafermin as compared to patients treated with placebo. Aldafermin-associated increase in low-density lipoprotein cholesterol, consistent with on-target inhibition of bile acid synthesis, was mitigated by co-administration of rosuvastatin. There was no observed signal for adverse cardiovascular events in this trial related to aldafermin.
A manuscript on the ALPINE 4 study has been accepted and published online ahead-of-print in Hepatology (Hepatology 2023; doi: 10.1097/HEP.0000000000000607).
About NGM Bio
NGM Bio is focused on discovering and developing novel, life-changing medicines for people whose health and lives have been disrupted by disease. The company’s biology-centric drug discovery approach aims to seamlessly integrate interrogation of complex disease-associated biology and protein engineering expertise to unlock proprietary insights that are leveraged to generate promising product candidates and enable their rapid advancement into proof-of-concept studies. As explorers on the frontier of life-changing science, NGM Bio aspires to operate one of the most productive research and development engines in the biopharmaceutical industry. All therapeutic candidates in the NGM Bio pipeline have been generated by its in-house discovery engine, always led by biology and motivated by unmet patient need. Visit us at www.ngmbio.com for more information.
FibroScan® is a registered trademark of Echosens SA.
Forward Looking Statements
Statements contained in this press release regarding matters that are not historical facts are “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995. Words such as “will,” “may,” “potential,” “belief,” “promising,” “compelling,” “aspires,” “aims” and similar expressions (as well as other words or expressions referencing future events, conditions or circumstances) are intended to identify forward-looking statements. These statements include those related to: the therapeutic potential of NGM Bio’s product candidates, including aldafermin; NGM Bio’s continued pipeline development, including any potential further development of aldafermin, and research and development and discovery engine output; the potential for aldafermin to treat patients with F4 NASH; and other statements that are not historical fact. Because such statements deal with future events and are based on NGM Bio’s current expectations, they are subject to various risks and uncertainties, and actual results, performance or achievements of NGM Bio could differ materially from those described in or implied by the statements in this press release. These forward-looking statements are subject to risks and uncertainties, including, without limitation, risks and uncertainties associated with the costly and time-consuming pharmaceutical product development process and the uncertainty of clinical success, including the risk that aldafermin may not prove to be safe, well-tolerated or effective; risks related to failure or delays in successfully initiating, enrolling, reporting data from or completing clinical studies, as well as the risks that results obtained in preclinical or clinical trials to date may not be indicative of results obtained in future trials; NGM Bio’s ability to identify and engage third-party partners for potential future business development arrangements, if any, and its ability to attract such partners; the time-consuming and uncertain regulatory approval process; NGM Bio’s reliance on third-party manufacturers for its product candidates and the risks inherent in manufacturing and testing pharmaceutical products; the sufficiency of NGM Bio’s cash resources and expected cash runway, including the risk that NGM Bio could utilize its available capital resources sooner than it currently expects and its need for additional capital; macroeconomic conditions (such as the impacts of the ongoing COVID-19 pandemic and global geopolitical conflicts, global economic slowdown, increased inflation, rising interest rates and recent and potential future bank failures); and other risks and uncertainties affecting NGM Bio and its development programs, including those discussed in the section titled “Risk Factors” in NGM Bio’s Quarterly Report on Form 10-Q for the quarter ended September 30, 2023 filed with the United States Securities and Exchange Commission (“SEC”) on November 2, 2023 and future filings and reports that NGM Bio makes from time to time with the SEC. Except as required by law, NGM Bio assumes no obligation to update these forward-looking statements, or to update the reasons if actual results differ materially from those anticipated in the forward-looking statements.
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