Eiger chalks up one win, one loss in rare disease pipeline

The north face of the Eiger
Ubenimex is cut, but avexitide hits the mark in post-bariatric hypoglycemia (Terra3 - CC BY-SA 3.0)

Eiger BioPharma has given up on one of its rare disease candidates after a second negative trial, but a midstage win for another drug has more than softened the blow.

The failed phase 2 trial with ubenimex in primary and secondary lymphedema of the lower limb—or swelling in the arms and legs due to a blockage—comes after the competitive protease inhibitor failed to hit the mark in pulmonary arterial hypertension earlier this year.

Eiger now says it has dropped the drug from internal development but will continue to support some investigator-led studies.

While disappointing, ubenimex’s demise was more than offset by Eiger’s other news, which was positive data in the phase 2 PREVENT study of avexitide (formerly exendin 9-39) in post-bariatric hypoglycemia (PBH), according to analysts at Jefferies.

With investors’ attention mostly focused on Eiger’s hepatitis delta drug lonafarnib as it starts phase 3, the PBH program has been “mostly under the radar” but could be “a key value driver, which could grow faster than expected,” they wrote in a research note.

There are around 150,000-200,000 gastric bypass or "bariatric" procedures for obesity each year in the U.S., and some of these patients develop PBH characterized by low blood sugars that occur two to three hours after a meal. It is thought to be caused by excessive insulin secretion after eating, resulting from elevated levels of the hormone GLP-1. For some patients the effects are devastating, leading to loss of consciousness and seizures in severe episodes.

In the 18-patient PREVENT trial, GLP-1 antagonist avexitide swept the board on primary and secondary endpoints when given as a subcutaneous injection once- or twice-daily after a test meal, with statistically significant reduction in after-meal blood glucose declines, as well as the need for rescue therapies to bring levels back up to normal ranges and after-meal insulin peaks.

The drug’s effects on study endpoints were also reinforced by positive data from continuous glucose monitoring on hypoglycemia episodes and glucose-related symptoms recorded using patient diaries.

While patients with mild PBH can manage the condition with dietary restrictions, those with more severe effects are treated with drugs octreotide, diazoxide, and acarbose, which have poor efficacy and tolerability, according to Jefferies.

“EIGR noted that many pts in ph.II PREVENT were refractory to these medications,” wrote the analysts, who suggested the clinical profile of avexitide could translate to an attractive price point if phase 3 testing goes to plan.

They think avexitide could reach the market as early as 2021 and could produce peak global revenues of around $361 million by 2026.

“We are very pleased by the results from PREVENT, our first outpatient study of avexitide in patients suffering from PBH,” said Lisa Porter, M.D., Eiger’s chief medical officer of metabolic diseases. “We look forward to meeting with regulatory authorities, both FDA and EMA, to discuss next steps.”