- Data demonstrate statistically significant, dose-dependent and clinically meaningful reductions in disease activity
- Results support NGM282 as a potential treatment for a variety of orphan bile acid-related diseases
SOUTH SAN FRANCISCO, Calif., March 24, 2015 (GLOBE NEWSWIRE) -- NGM Biopharmaceuticals, Inc., a privately-held biotechnology company that seeks to translate powerful biology into transformative medicines, today reported positive results from a Phase 2 trial of NGM282 in patients with primary biliary cirrhosis (PBC). NGM282, an engineered protein variant of the human hormone FGF19, demonstrated statistically significant, dose-dependent and clinically meaningful reductions in alkaline phosphatase (ALP), a primary indicator of disease activity, as well as substantial reductions in 7α-Hydroxy-4-cholesten-3-one (C4), a marker of bile acid synthesis. These data suggest that NGM282 is a potent regulator of bile acid synthesis.
"This Phase 2 study demonstrated that NGM282 causes significant improvements on established markers of disease progression and could deliver meaningful clinical benefits to patients with PBC," said William Rieflin, Chief Executive Officer of NGM. "However, in light of treatment alternatives that may be available to PBC patients before our daily injectable therapeutic could gain approval, we are pursuing additional studies of NGM282 in other orphan bile acid-related diseases where the pronounced activity on bile acid synthesis as demonstrated by C4 reduction may provide benefit."
The study was a double blind, placebo-controlled trial in 45 patients randomized 1:1:1 to daily injections of 0.3 mg or 3 mg doses of NGM282 or placebo. Study subjects had a confirmed PBC diagnosis with an inadequate response to ursodeoxycholic acid (UDCA), the current standard of care, defined as an elevated ALP level greater than 1.67 times the upper limit of normal while on therapeutic doses of UDCA for at least 12 months. All subjects continued with UDCA treatment during the study. Patients with pruritus, hyperlipidemia and other comorbidities commonly seen in PBC were allowed to enroll in the study.
Data from the trial demonstrated a statistically significant and clinically meaningful percentage reduction in ALP from baseline to day 28 in both NGM282 treatment arms (0.3 mg = -15.8 percent, p-value = 0.009; 3 mg = -19.2 percent, p-value = 0.003). Significant reductions of other key markers of liver injury, such as ALT and AST, were also observed for both NGM282 treatment groups.
Importantly, NGM282 did not exacerbate pruritus, which is a symptom frequently experienced by many PBC patients that substantially impacts quality of life. More than 50 percent of study subjects had pruritus at baseline, which was balanced across the three groups. All subjects with pruritus at baseline treated with 3 mg of NGM282 had either an improvement or no worsening of their pruritus during the study. Two subjects without pruritus at baseline, one in each treatment arm, presented with mild, transient pruritus during the study period. However, the overall study assessment demonstrated that there was no significant evidence of drug-induced pruritus in any study arm.
NGM282 had a favorable safety and tolerability profile with no identified safety signals. Most adverse events were mild, with a single serious adverse event during the study period that was deemed unrelated to treatment by the investigator. The most common adverse events were mild headache and mild lower gastrointestinal (GI) symptoms (predominantly diarrhea and loose stools). The lower GI symptoms were observed in 21 percent of the 0.3 mg and 43 percent of the 3 mg cohorts, compared to 13 percent of the placebo group.Mild injection site reactions (predominantly erythema or redness) were also observed more frequently with NGM282. There was no evidence of an immunogenic response to NGM282 during or after the treatment period. All lipid parameters and triglycerides remained stable during the treatment period.
"These data demonstrate NGM282's potent impact on bile acid synthesis, as measured by reductions in serum C4, translating into improvement in markers of disease in PBC patients," said Alex DePaoli, M.D., Chief Medical Officer of NGM. "PBC is one of many bile acid-related diseases that result from dysregulated bile acid synthesis or transit. This study supports the potential utility of NGM282 in treating a variety of these orphan diseases."
About NGM Biopharmaceuticals, Inc.
NGM Biopharmaceuticals applies fundamental discoveries in human pathophysiology to create novel biologics for the treatment of a broad spectrum of life-threatening diseases. NGM's lead compound, NGM282, a wholly-owned asset, is being studied in a variety of bile acid-related diseases and nonalcoholic steatohepatitis. NGM has established collaborations with Merck, MedImmune, Daiichi Sankyo and JDRF. NGM is a privately-held company backed by investments from The Column Group, Merck, Prospect Ventures, Rho Ventures, Tichenor Ventures, Topspin Partners and other leading investors around the world. For more information, please visit www.ngmbio.com.