GenFit’s lead product candidate elafibranor snagged Breakthrough Therapy Designation from the U.S. Food and Drug Administration as a treatment for Primary Biliary Cholangitis (PBC) following strong Phase II results that demonstrated the safety and efficacy of the medication.
Dean Hum, COO of GenFit.
GenFit’s lead product candidate elafibranor snagged Breakthrough Therapy Designation from the U.S. Food and Drug Administration (FDA) as a treatment for Primary Biliary Cholangitis (PBC) following strong Phase II results that demonstrated the safety and efficacy of the medication.
At the International Liver Congress earlier this month, France-based GenFit shared data that showed positive results from both the 80 mg and 120 mg doses tested in the trial. The abstract describing Phase II PBC data was so strong and promising that it was selected as “Best of ILC 2019” at this year’s conference. Following the positive results from the Phase II trial in PBC, GenFit expects to move elafibranor into Phase III trials later this year, Dean Hum, GenFit’s chief operating officer, told BioSpace in a telephone interview.
“We hit strongly on the endpoints with both doses. These results are highly significant,” Hum said.
When elafibranor is moved into the Phase III trial, Hum said it will likely be set up for a one-year study, longer than the two-week double-blind study that generated the positive Phase II data.
PBC is a chronic disease in which bile ducts in the liver are gradually destroyed. The damage to bile ducts can inhibit the liver’s ability to rid the body of toxins, and can lead to scarring of liver tissue known as cirrhosis. Elafibranor is a first-in-class double peroxisome proliferator-activated receptor alpha and delta (PPAR alpha/delta) agonist. Not only is it showing promise in treating PBC, but the drug is also making significant headway as a potential treatment for nonalcoholic steatohepatitis (NASH). Currently, there are no approved treatments for NASH, but GenFit hopes that elafibranor will be among the first approved by regulatory agencies.
In the Phase II PBC trial, patients who were treated with both doses of elafibranor showed a significant decrease of alkaline phosphatase (ALP) levels, which was the primary endpoint. In addition to significant reductions in ALP, patients in both elafibranor-treated groups showed improvements in other PBC markers, including gamma-glutamyl transferase (GGT), lipid markers (total cholesterol, LDL and triglycerides), and anti-inflammatory markers (IgM, CRP, haptoglobin and fibrinogen), GenFit said.
Hum said the data regarding improvements in GGT, lipid and anti-inflammatory markers is consistent with what the company saw in its Phase II trial in NASH, which he said was excited to see. Based on what has been seen so far, Hum said he anticipates the Phase III NASH trial to continue confirming these results.
One surprising discovery, which Hum said could be quite important for future commercialization, is that elafibranor appears to be able to reduce concerns of pruritis, which is itching associated with patients who have chronic liver diseases such as PBC and NASH. In the Phase II trial, approximately 70 percent of the patients complained of pruritis. For the patients who were dosed with elafibranor, there was no worsening of pruritis and in some cases, there were instances where pruritis symptoms were reduced, Hum said. In placebo, there was a worsening of it, he added.
“This drug is hitting on all of the points,” Hum said. “There are (so far) no safety issues, no toxicity issues and no tolerability issues. I think that speaks very strongly for this in PBC patients.”
With Breakthrough Therapy Status in hand, as well as the strong Phase II results, the company plans to meet with the FDA later this year to develop protocols for the Phase III trial. Hum said he anticipates that the Phase III trial could begin by the end of 2019 or in the early months of 2020.
The Phase III PBC trial could begin about the same time that GenFit anticipates top-line Phase III interim data readout for elafibranor in the NASH fibrosis trial. Hum noted that elafibranor is showing significant promise in this space of unmet need. Elafibranor is showing signs that it can actually reduce or get rid of NASH in a patient. If that’s the case, Hum said the liver could then actually begin to heal itself from the fibrosis associated with NASH.
With the potential of elafibranor to be approved in multiple indications, as well as other potential commercial products in its pipeline, Hum said GenFit is scaling the company in anticipation. Part of that scaling was the decision to open an office in Massachusetts, Hum said. That Bay State office provides the company with a toehold to develop a marketing and sales team for its future products.
“We have a very well qualified team in Boston with a lot of talent there and we hope to continue to attract top talent as we move forward,” Hum said.
