FDA Action Alert: Mirum and Kite/Gilead



The U.S. Food and Drug Administration (FDA) is wrapping up the end of September and beginning October with two PDUFA dates. Here’s a look.

Mirum Pharma’s Maralixibat for Cholestatic Pruritus in Alagille Syndrome

Mirum Pharmaceuticals has a target action date of September 29, 2021, for its New Drug Application (NDA) for maralixibat to treat cholestatic pruritus in patients with Alagille syndrome. The drug is an oral apical sodium-dependent bile acid transporter inhibitor. The NDA is being evaluated under a Priority Review pathway.

Alagille syndrome (ALGS) is a rare genetic disorder. In it, bile ducts are abnormally narrow, malformed and fewer in number. This leads to bile accumulating in the liver, which leads to progressive liver disease. ALGS occurs in about one in every 30,000 people.

To date, more than 1,600 people have received maralixibat, including more than 120 children. It is being developed for Alagille syndrome, progressive familial intrahepatic cholestasis (PFIC), and biliary atresia. In the ICONIC Phase IIb ALGS trial, the drug demonstrated significant decreases in bile acids and pruritus (severe itching) compared to placebo, as well as a decrease in xanthomas and accelerated growth long-term. In a Phase II PFIC study, a genetically defined subgroup of BSEP deficient (PFIC2) patients responded to the drug with an increase in transplant-free survival.

Mirum has inked several licensing deals with companies to develop and commercialize maralixibat in several parts of the world. On September 21, 2021, Mirum and Takeda Pharmaceutical entered into an exclusive licensing agreement to develop and commercialize maralixibat in Japan for ALGS, PFIC, and biliary atresia. On July 26, Mirum and GC Pharma inked a deal to develop and commercialize the drug in South Korea for the same three indications. And on April 29, the company and CANbridge Pharmaceuticals signed a deal to develop and sell the drug in Greater China.

On September 13, 2021, Mirum announced it had submitted a Marketing Authorization Application (MAA) for cholestatic liver disease for ALGS to the European Medicines Agency (EMA). At the same time, it indicated that its MAA for PFIC2 was withdrawn with plans to re-submit after data from the ongoing MARCH-PFIC Phase III trial was available.

Gilead/Kite’s Tecartus for R/R B-Cell Precursor ALL

Kite, a Gilead Sciences Company, has a target action date of October 1 for its supplemental Biologics License Application (sBLA) for Tecartus (brexucabtagene autoleucel) in adults with relapsed or refractory B-cell precursor acute lymphoblastic leukemia (ALL). Tecartus is a chimeric antigen receptor (CAR) T-cell therapy. The sBLA is under Priority Review.

The submission was based on primary analysis of the ZUMA-3 Phase I/II study. In the pivotal Phase II part of the trial, 71 patients with relapsed or refractory disease were enrollees. In treated patients, 47% had three or more previous therapies. At a median follow-up of 16.4 months, 71% of patients receiving the therapy had a complete response (CR) or CR with incomplete hematological recovery (CRi), with 31% in ongoing response at the data cut-off. Of those responding, 97% had deep molecular remission, with undetectable minimal residual disease (MRD). They also had a median overall survival (OS) that was not reached at the time of cut-off.

As is common with CAR-T therapies, there were side effects — 95% of patients reported Grade 3 or greater adverse events, with anemia (49%) and pyrexia (36%) the most common. Grade 3 or greater cytokine release syndrome (CRS) and neurologic events were observed in 24% and 25% of patients, respectively, and were typically reversed with treatment.

“Outcomes in adults with acute lymphoblastic leukemia are poor relative to what is observed in children, with less than half of people over 20 years of age expected to survive the illness,” said Bijal Shah, ZUMA-3 investigator and medical oncologist, Moffitt Cancer Center, Tampa, Florida, in a June statement. “It is on this background that CAR T-cell therapy with brexucabtagene autoleucel was tested in adults with relapsed B-ALL in ZUMA-3. In this international, multicenter study, we observed a response rate of 71%. Importantly, the majority of these responses were associated with undetectable minimal residual disease.”

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