Clinical Trials

Date: 2017-04-22

Type of information: Presentation of results at a congress

phase: 2

Announcement: presentation of results at The International Liver Congress 2017

Company: BMS (USA - NY)

Product: BMS-986036 (Pegylated FGF21)

Action mechanism: antibody drug conjugate (ADC). BMS-986036 is an investigational pegylated analogue of human fibroblast growth factor 21 (FGF21). Bristol-Myers Squibb exclusively licensed the rights to research, develop and commercialize BMS-986036 from Ambrx, Inc. Bristol-Myers Squibb Company (NYSE: BMY) and Ambrx, Inc. today announced a collaboration under which Bristol-Myers Squibb will receive exclusive worldwide rights to research, develop and commercialize biologics based on Ambrx’s research surrounding the Fibroblast Growth Factor 21 (FGF-21) protein, for potential use in treating type 2 diabetes, and the Relaxin hormone, for potential use in treating heart failure. Derivatives of FGF-21 and Relaxin were developed using Ambrx’s unique ReCODETM platform technology to modify the native proteins with amino acid building blocks beyond the common 20 to engineer enhanced versions for investigation for therapeutic use. Under the terms of the agreement, Bristol-Myers Squibb will make an upfront payment of $24 million to Ambrx. In addition, Bristol-Myers Squibb will make potential milestone payments and royalty payments on worldwide sales for both programs. Bristol-Myers Squibb and Ambrx will also enter research collaborations for both programs. FGF-21 is a naturally occurring protein that has been characterized as a potent metabolic regulator, and has been shown to lower blood glucose, elevate good cholesterol and promote weight loss in preclinical studies. The lead compound in this program, ARX618, or PEG-FGF-21, is in the final stages of preclinical development.Ambrx Initiates Collaboration with Bristol-Myers Squibb for Discovery, Development of Next-Generation Antibody Drug Conjugates by ambrxmed | May 3, 2013 | Press Releases | SAN DIEGO May 3, 2013 Ambrx today entered into a collaboration agreement with Bristol-Myers Squibb (NYSE: BMY) for the discovery and development of novel antibody drug conjugates using Ambrx’s protein medicinal chemistry technology. Under terms of the agreement, Ambrx will receive an upfront payment of $15 million, funding for discovery and research activities, and potential development, regulatory and sales based milestone payments of up to $97 million per product resulting from the collaboration. Bristol-Myers Squibb will receive worldwide rights to develop and commercialize products resulting from the collaboration, and Ambrx is eligible to receive royalties on net sales. Additional terms were not disclosed. “Bristol-Myers Squibb is a global biopharmaceutical leader with expertise developing and commercializing novel medicines for the treatment of cancer and other diseases, and we are pleased to enter into a third collaboration with the company to include another aspect of our technology platform,” said Lawson Macartney, Ph.D., chief executive officer of Ambrx. “We look forward to working together to further utilize Ambrx’s technology to discover and advance these antibody drug conjugates for oncology indications.” Ambrx and Bristol-Myers Squibb entered into two separate agreements in September 2011 to research, develop and commercialize biologics created with Ambrx’s protein medicinal chemistry technology. These therapeutic candidates, which target the Fibroblast Growth Factor 21 (FGF-21) protein for the potential treatment of type 2 diabetes, and the Relaxin hormone for the potential treatment of heart failure, are being developed by Bristol-Myers Squibb.

Disease: NASH (non-alcoholic steatohepatitis)

Therapeutic area: Hepatic diseases - Liver diseases

Country: USA

Trial details:

• The purpose of the MB130-045 study is to determine whether BMS-986036 is effective in the treatment of subjects with Non-alcoholic Steatohepatitis (NASH). MB130-045  was a multicenter, randomized (1:1:1), double-blind, placebo-controlled study in adults with body mass index ?25 kg/m2, biopsy-confirmed NASH (F1-F3), and hepatic fat fraction ?10%, assessed by magnetic resonance imaging-proton density fat fraction (MRI-PDFF), a noninvasive measurement of liver fat. Randomization was stratified by diabetes status.
• Patients received subcutaneous injections of BMS-986036 10 mg daily (n=25), BMS-986036 20 mg weekly (n=23), or placebo (n=26) daily for 16 weeks. The primary efficacy endpoint was absolute change in MRI-PDFF at Week 16. Exploratory endpoints included serum Pro-C3 (N-terminal type III collagen propeptide, a fibrosis biomarker), enzymes alanine aminotransferase (ALT) and aspartate aminotransferase (AST), and, in a subset of patients, liver stiffness, assessed by MR elastography (MRE). (NCT02413372)

Latest news:

• • On April  22, 2017, BMS announced data from a Phase 2 study of BMS-986036, an investigational pegylated analogue of human fibroblast growth factor 21 (FGF21) in patients with biopsy-confirmed nonalcoholic steatohepatitis (NASH) (F1-F3). The study achieved its primary endpoint of significant reduction in liver fat versus placebo. Statistically significant improvements were also seen in prespecified exploratory endpoints including biomarkers of fibrosis, metabolic parameters and markers of liver injury. These data were presented at a late-breaking oral presentation at EASL: The International Liver Congress in Amsterdam.
• Among the 74 patients treated, 68 were assessed by MRI-PDFF at both Baseline and Week 16. Liver biopsy was conducted to confirm NASH at Baseline. At Week 16, both dosing regimens of BMS-986036 (10 mg daily or 20 mg weekly) significantly reduced liver fat as measured by MRI-PDFF versus placebo (6.8% and 5.2%, respectively, vs. 1.3%, p=0.0004 and p=0.008). The 10 mg daily dose resulted in 57% of patients (13/23) reaching ?30% relative risk reduction. The 20 mg weekly dose resulted in 52% of patients (11/21) reaching ?30% relative risk reduction. Both dosing regimens also improved Pro-C3 (a serum biomarker of fibrosis), magnetic resonance elastography (MRE, a measure of liver stiffness), as well as adiponectin, ALT and AST (markers of liver injury). Improvements in triglycerides, low density lipoprotein (LDL), and high density lipoprotein (HDL) were also observed in the treatment groups.
• Overall, BMS-986036 had a favorable safety profile, with no deaths or serious adverse events related to treatment, and no discontinuations due to adverse events. The most frequent adverse events were diarrhea (13% and 22%, respectively, vs. 8% in placebo), nausea (16% and 13%, respectively, vs. 8%), and frequent bowel movements (20% and 0%, respectively, vs. 0%), none of which were severe.

 

Is general: Yes