NGM Bio unveils positive PhII NASH results to some unimpressed investors
NGM Bio got up early this morning in South San Francisco ready to proclaim an interim win of its lead NASH drug, aldafermin, in the fourth and final leg of a lengthy Phase II program. The results of comparing drug to placebo were positive, the company said, setting up some expectations for a final readout in early 2020.
But investors weren’t quite buying it. The stock $NGM has slid around 18%.
So what’s wrong?
It may be helpful to remember, first of all, that NASH is a blockbuster sized market that’s enticed multiple biotech players from Intercept and Madrigal to Genfit and Viking, and any signs of early hope or doom — especially as compared to other rivals, despite the dangers of cross-trial comparisons — could cast different lights on the data.
With that, here’s what NGM has reported about the 38-patient trial: A 24-week treatment with once-daily 1 mg aldafermin, or NGM282, met the primary endpoint regarding changes in absolute liver fat content achieving a drop of 7.9% versus 2.0% on placebo as measured by MRI-estimated proton density fat fraction (p<0.05).The change in relative LFC came in at a dramatic -39.6% over -5.9% in the placebo arm.
The company also noted that 72% of the aldafermin group achieved 5% or more absolute reduction in LFC, compared to 17% of those taking placebo.
That’s indeed positive, and roughly in line with the Phase II data Madrigal previously reported for their MGL-3196 (-36.3% relative reduction on drug vs 9.6% on placebo). But it fell short of the 57-60% median relative change and 77-91% responder rate that Viking posted last year, sparking a surge in share price.
Something else might also be driving the concern: a spike in cholesterol levels (LDL-C to be specific) at week 2 of treatment. While NGM contends it’s nothing they didn’t know from previous Phase II cohorts, that it’s a direct effect of FGF19’s inhibition of the classical bile acid synthesis pathway and that it was quickly resolved by statin treatment, a mean increase of 47.6 mg/dL in LDL-C relative to a 103.5 mg/dL baseline could be alarming to a patient population that already has heightened cardiovascular risks.
CEO David Woodhouse maintained they are pleased with the interim findings, part of an expansive clinical campaign funded by a $200 million-plus partnership with Merck and a $107 million IPO a few months ago.
“Aldafermin continues to be differentiated with what we believe is an industry-leading profile as a monotherapy for the potential treatment of NASH, as few drugs in development for this disease have shown meaningful metabolic, anti-inflammatory and anti-fibrotic activity,” CMO Hsiao Lieu added in a statement. “Throughout our Phase 2 program, we’ve seen a relationship between aldafermin’s impact on biomarkers of disease and subsequent histology results. To that end, we look forward to the biopsy data readout for Cohort 4, which will further inform planning activities for our Phase 3 study.”