Genfit goes to China with a deal worth up to $228M for NASH drug
Fresh off the high of its Nasdaq IPO debut, and the low of comparisons to Cymabay — whose NASH drug recently stumbled — Genfit on Monday unveiled an up to $228 million deal with transpacific biotech Terns Pharmaceuticals to develop its flagship experimental liver drug — elafibranor — in Greater China.
The deal comes weeks after Genfit $GNFT issued a fiery defense of its dual PPAR agonist elafibranor, when competitor Cymabay’s PPARδ agonist, seladelpar, fizzled in a snapshot of data from an ongoing mid-stage trial. The main goal at the end of 12 weeks was for seladelpar to induce a statistically significant improvement in liver fat content, but data showed that patients on the placebo actually performed better.
The two treatments belong to a family of drugs that activate proteins called peroxisome proliferator-activated receptors (PPARs), which regulate gene expression. Existing evidence suggests that in the liver, PPAR agonists play a role in bile acid synthesis, inflammation, fibrosis and lipid metabolism.
NASH is an untreated fatty liver disease that has ravaged the developed world, creating a lucrative target that has sparked a flurry of drug development from biopharma firms big and small. It is characterized by a buildup of excess fat in the liver that induces chronic inflammation and eventually culminates in scarring that can lead to cirrhosis, liver failure, cancer and death.
Dubbed the silent disease, it is hard to diagnose in the early stages, making it difficult to estimate its prevalence, but studies show that it afflicts up to 12% of the adult population in developed countries. Although there are no approved drugs for the disease, the size of the NASH market is expected to cross $20 billion by 2025.
While other major NASH contenders — Gilead $GILD (fail in Phase III) and Intercept $ICPT (mixed win in Phase III) — have disclosed the top-line numbers of their late-stage trials, Genfit is expected to come out with its Phase III interim results by the end of 2019, or early 2020.
Late-stage data on Intercept’s drug — obeticholic acid (OCA) — showed it induced a statistically significant improvement in fibrosis, but not NASH resolution, and a higher-than-expected number of patients dropped out due to the pesky side-effect of itching. In contrast to Intercept, Genfit has emphasized that elafibranor’s potential in NASH resolution and reducing CV risk along with a benign safety and tolerability profile have set it apart.
“We think we’re going to be the first drug on the market that can resolve NASH,” Genfit’s COO Dean Hum stressed in an interview with Endpoints News.
He suggested that Cymabay had “made a mistake” to focus on liver fat, when they should have concentrated on inflammation and fibrosis — the factors that constitute NASH resolution.
But some analysts are not quite as convinced.
In the aftermath of the Cymabay data, Baird’s Brian Skorney suggested seladelpar and elafibranor are beginning to appear more similar than different.
“Though the two medications were thought to have differentiated mechanisms of action, it seems that this may not be the case, as seladelpar’s data suggest that the medication does not reduce liver fat, which is similar to what we have seen from earlier trials of elafibranor. This leads us to believe that these two PPARs look much more similar than different. Hence, CymaBay may be at a significant disadvantage moving forward as we believe that even if PPAR agonism is successful in Genfit‘s Phase 3 trial, without any clear signs of differentiation, CymaBay may have an uphill battle as they work to catch up to Genfit in NASH. If elafibranor fails in NASH, it would probably be predictive of the outcome of seladelpar in NASH. Either way, we think this makes the PPAR class, as a whole, look like a less significant competitive threat to OCA.”
While the bulk of obesity and related diseases have traditionally been the wheelhouse of the Western world, rapid urbanization in parts of Asia has normalized sedentary lifestyles and overnutrition, setting the stage for obesity in epidemic proportions. A study published in 2017 suggests the incidence of obesity has been increasing at an alarming rate, particularly in China, Japan and India. “The number of obese Chinese people was below 0.1 million in 1975, rising to 43.2 million in 2014 and accounting for 16.3% of global obesity,” researchers found.
Genfit’s new partner Terns is well versed in NASH. Last year, it joined forces with Eli Lilly to develop the US drugmaker’s early-stage NASH assets, in addition to its own.
Under the deal, Terns — which has operations in California, as well as a setup in China — will hand over $35 million upfront, in addition to up to $193 million in potential milestone payments to develop Genfit’s late-stage asset elafibranor for use in NASH and primary biliary cholangitis (PBC).
A key reason behind the deal was that since elafibranor’s existing late-stage study does not include Chinese patients, another Phase III study including such patients would be required for Chinese approval, Pascal Prigent, Genfit’s executive VP of marketing and commercial development, told Endpoints News.