Intercept Pharmaceuticals (NASDAQ: ICPT) said today it was on track to ask US and European regulators this year to approve what could be the first drug for an advanced liver disease that poor diet and exercise habits have turned into a quiet epidemic.
The disease is called nonalcoholic steatohepatitis, or NASH, and as the name implies, it’s similar to what happens to people who chronically abuse alcohol. The liver becomes inflamed, stiff, and scar tissue builds up; thousands of people in the US alone who have been diagnosed with NASH need liver transplants to survive. Intercept’s drug, a once-a-day pill called obeticholic acid (OCA), is meant to reverse the scarring and return some function back to the liver.
Intercept’s presentation Thursday at the International Liver Congress meeting in Vienna, Austria, reiterated findings from its key Phase 3 study REGENERATE that OCA significantly reduced the amount of scarring, or fibrosis, in livers of people confirmed with NASH. But OCA did not resolve NASH—that is, reverse of a panel of symptoms such as inflammation—in a statistically meaningful way. Intercept reported those broad outlines two months ago. Intercept and the FDA have agreed that only one of these two goals would be necessary for OCA to potentially qualify for approval.
In an interview Thursday, Intercept’s SVP of medical affairs Gail Cawkwell confirmed that Intercept will submit OCA for approval later this year.
Intercept used this week’s meeting to unveil an analysis of a subset of the REGENERATE study, about 70 percent of the 931 enrolled patients, faring better than the full set. Still, investors sent Intercept shares down nearly 13 percent, perhaps because a focus on a smaller group of patients can make observers nervous. “We believe investors are interested in the detailed analyses for the [larger] population and we will be looking for more details,” wrote RBC Capital Markets analyst Brian Abrahams in a research note.
The smaller group counted those who reached 18 months of treatment and received a follow-up liver biopsy, an important milestone for trial investigators to measure a patient’s progress. Measuring them was “per protocol”—part of the trial plan all along—Intercept said, meant to reflect how a drug “is more likely to behave in clinical practice,” said Cawkwell.
In the per-protocol group, 38 percent of patients taking the OCA 25 mg dose, which Intercept is likely to take to market, showed at least one stage of improvement in fibrosis. In the broader group, it was 23.1 percent. Those taking placebo also showed a gain in the smaller group, 23.2 percent, compared with 11.9 percent in the larger group. The per-protocol subset, the full patient set, and an even larger set of patients being evaluated for safety will all be submitted to regulators.
Getting to market isn’t the only hurdle for Intercept and its rivals, which include a long list of pharmaceutical companies large and small. NASH remains something of a mystery disease. It’s not clear why some people with early signs of NASH’s precursor, nonalcoholic fatty liver disease, progress to NASH and some don’t.
Before Intercept’s presentation, liver specialists in separate presentations highlighted two areas of uncertainty about the disease. Susceptibility to NASH varies from patient to patient, and the diagnostic tools used to determine which patients are appropriate for a NASH drug, if one is approved, are a work in progress.
This uncertainty could hang over the head of NASH developers if their products come to market. “There is significant unpredictability in determining which patients progress on the disease versus those that actually regress over time,” wrote SVB Leerink analyst Pasha Sarraf in a note to investors. “While this is not a surprise, it confirms our view that companies will have a difficult time convincing payers that all patients are in dire need of interventions.”
OCA certainly won’t be for everyone with signs of fatty liver disease. “Patients with advanced fibrosis due to NASH are in most need for treatment,” said Cawkwell. She said that REGENERATE and more studies with large data sets will help solidify the role of diagnostics. “Many doctors have these tools in their offices and are already using them,” she said. “What we need is to correlate the results with measurements over time in a clinical setting.”
Intercept also gave more information about safety. The biggest problem with OCA is itching, known medically as pruritis. It can be severe. Nine percent of people in REGENERATE taking the higher dose of OCA had to drop out because of the itching. Cawkwell noted that more than half those dropouts had no choice; their symptoms triggered a halt based on the trial design. The new data also showed that the most onset of pruritis occurred in the first three months of treatment, and that it was mild to moderate in 93 percent of patients. Beyond the confines of a regulated clinical trial, it’s unclear if more patients would agree to stick with the drug if they knew some of these results. Intercept has been asking patients to report how the pruritis is affecting their quality of life but hasn’t finished an analysis. “It’ll give us a better sense how to characterize it better and help doctors counsel their patients better,” said Cawkwell.