NGM exits Nash, in latest setback for the field

 Despite NGM Bio’s trial in Nash hitting some secondary endpoints the company has decided not to push on with the programme, saying it will not be ploughing cash into another study. The phase 2b Alpine 2/3 study, in patients with stage 2/3 fibrosis, failed to meet the primary endpoint, fibrosis improvement by at lease one stage with no worsening of Nash, versus placebo. The knockback caused the company's shares to plummet 40% in early trading. Alpine 4, in patients with very advanced fibrosis and compensated cirrhosis, will continue, and NGM has an option to jump on board with MK-3655, an insulin sensitiser out-licensed to Merck & Co; effectively, however, one of the investment communities most closely-followed Nash plays looks to have thrown in the towel in this disease. Several other companies are looking at fibroblast growth factors (see table) and will be hoping for a better outcome. But the news is another reminder that Nash is an incredibly tough target, despite a huge amount of hope, and hype, in the past few years. NGM's attention will now turn to its remaining pipeline, which includes NGM621 in phase 2 in geographic atrophy. The project is an anti-complement C3 antibody, much like Apellis’s intravitreal pegcetacoplan, which is due to report phase 3 data in the third quarter.

Phase 2 fibroblast growth factors for Nash
Product	Company	Mechanism of Action	Note
Pegbelfermin (BMS-986036)	Bristol-Myers Squibb/Ambrx	FGF21 stimulant	Falcon 1 and 2 studies had primary completion dates in Sept 2020
Aldafermin	NGM	FGF19 analog	Alpine 2/3 study failed, Alpine 4 ongoing PC June 22
Efruxifermin (AKR-001)	Amgen/Akero	FGF21 stimulant	Two parallel Ph2b in fibrosis stage 2/3 (Harmony) and F4 to start this year, data Q3 2022
MK-3655 (NGM313)	Merck/NGM	FGFR1c antibody	Ph2b (fibrosis stage 2/3) PC 2023
BIO89-100	89bio	FGF21 stimulant	Ph2b Enliven expected to start Q2 (fibrosis stage 2/3)
Source: Evaluate Pharma, clinicaltrials.gov https://www.evaluate.com/vantage/articles/news/snippets/ngm-exits-nash-latest-setback-field