Company: NGM Biopharmaceuticals
Drug name: Aldafermin
Mechanism: FGF19 analog
Stage: Phase 2b
Next readout: Preliminary data from phase 2b ALPINE 2/3 study by the end of 2020
NGM Bio’s aldafermin is an engineered version of the hormone FGF19, which modulates two receptors: FGFR4, which regulates bile acid synthesis in the liver, and FGFR1c, a signaling receptor in body fat that regulates the creation of new fats, glucose management and body weight.
In October, NGM reported interim data showing that aldafermin beat placebo at reducing liver fat in 78 patients with stage 2 or stage 3 fibrosis after 24 weeks of treatment. Nearly three-quarters (72%) of the patients treated with a daily 1-mg dose of aldafermin had a 5% or greater absolute reduction in liver fat compared with 17% of those on placebo. And of the aldafermin patients, 28% achieved a normal liver fat content after 24 weeks, versus none in the placebo arm. The data come from the fourth cohort of the study.
The results were consistent with 12-week results announced in 2018, where the same dose of aldafermin led to improvements in liver enzymes, liver fat and other measures of NASH in a trial without a placebo arm. But, wrote Jefferies analysts at the time, “on a numerical basis the results today appear slightly worse.” Treating the patients for longer didn’t lead to “marked improvement” in liver fat or other measures, they wrote.
“Regardless, NGM's aldafermin remains one of the more interesting drugs for NASH, demonstrating both resolution in NASH and improvement/reversal of fibrosis. However, we think commercially, a daily injectable will more likely be a niche product based on our doctor checks and more focus will be on orals like ICPT's OCA, which is under FDA review and is set to launch next year,” the analysts wrote.
NGM expects to post topline results for cohort 4 in the first quarter of 2020 and plans to report preliminary data from ALPINE 2/3, its phase 2b study of aldafermin, by the end of 2020. It hopes to move the program into phase 3 on the strength of those data.