CymaBay PBC Drug Hits Phase 3 Goals With Signs of Side Effect Advantage

Xconomy San Francisco — 

CymaBay Therapeutics’ investigational drug seladelpar succeeded in a late-stage trial in patients with primary biliary cholangitis (PBC), producing results that suggest it could have a key side effect advantage compared to a drug currently used to treat the rare liver disease.

Patients with PBC, which damages the bile ducts of the liver, are initially treated with ursodeoxycholic acid (UDCA). When UCDA isn’t an option or doesn’t work well enough, Intercept Pharmaceuticals (NASDAQ: ICPT) drug obeticholic acid (Ocaliva) is the next option.

However, one of the most common side effects of the Intercept drug is pruritis, or itching—a common PBC symptom that can affect patients’ quality of life. Newark, CA-based CymaBay (NASDAQ: CBAY) aims to show that seladelpar should be the go-to second-line treatment based on its efficacy and, potentially, its ability to address pruritis associated with the buildup of bile acids that characterizes PBC.

On Monday the company reported that 78.2 percent of patients who received 10 mg of its experimental drug in a Phase 3 trial met its main goal, which was to show efficacy according to the overall response rate, defined as those whose levels of alkaline phosphatase, an enzyme linked to PBC, and bilirubin reached certain predefined levels at three months. Of patients who received a 5 mg dose, 57.1 percent met that goal; 12.5 percent of patients who received a placebo did so. For more than a quarter of patients in the 10 mg group, their alkaline phosphatase levels normalized after three months compared to 0 percent of those who received a placebo.

Shares of CymaBay closed up 37 percent Monday at $4.88 per share, up from $3.55 per share on Friday.

CymaBay’s prelimary results come less than two weeks after the FDA lifted a hold on clinical trials for seldepar, which the company was also testing in patients with nonalcoholic steatohepatitis (NASH) and the rare liver disease primary sclerosing cholangitis (PSC). The decision ended the PBC trial early. In the wake of the agency’s decision to remove the hold, the company said it would focus its efforts on advancing the drug for that condition.

Patients in the 10 mg group with pruritis considered moderate to severe saw an average reduction of 3.2 points from baseline on a scale measuring the symptom of the intensity compared to patients who received a placebo, whose saw an average 1.6 point reduction.

The label for the Intercept treatment warns of the potential for severe pruritis, and lists pruritis among the most common adverse reactions associated with the drug.

SVB Leerink analysts, in a research note, wrote that CymaBay could establish “a key point of differentiation” from the Intercept offering if it demonstrates an improvement in the symptom.

“With pruritus a key symptom for PBC patients, we believe agents that show an improvement in pruritus would likely be used preferentially to those that exacerbate this symptom,” the analysts wrote.

The drug appeared to be well tolerated by patients; adverse events that occurred were similar across the groups who received the drug and the placebo group.

CymaBay plans to start enrollment of PBC patients in a new Phase 3 trial of seladelpar, this one intended to produce data to submit to the FDA for its review, in the first quarter of 2021, president and CEO Sujal Shah said on a conference call Monday. Charles McWherter, the company’s chief scientific officer, said results from that trial would guide whether the company would look to claim the drug could relieve that symptom in an FDA submission.

“I would think that across the seldepar development program, both with these results, as well as the results that we’ve also presented on pruritis in the open-label study, if we were to hit it again I think that really strengthens the reproducibility of the effect,” he said on the call. “It makes it a much stronger case that we would for sure seek to put that into the label.”