Mapi-Pharma Ltd.

Pictured: Exterior of the FDA headquarters in Maryland/ iStock/Grandbrothers Regeneron’s Biologics License Application for its bispecific antibody odronextamab in relapsed/refractory follicular lymphoma and diffuse large B-cell lymphoma was hit with a regulatory setback Monday, as the company announced that it has been issued Complete Response Letters from the FDA. According to Regeneron, the “only approvability issue” cited by the FDA in its Complete Response Letters (CRLs) “is related to the enrollment status of the confirmatory trials.” The CRLs included one for relapsed/refractory follicular lymphoma (R/R FL) and another for relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL), each after two or more lines of systemic therapy. Regeneron also noted that the CRLs did not reveal any approval issues with odronextamab’s efficacy or safety, trial design, labeling or manufacturing. The company has been enrolling patients in multiple Phase III trials for the drug as it looks to treat lymphoma patients in earlier lines of treatment. However, the FDA required that the trials include both dose-finding and confirmatory portions. Enrollment in dose-finding had already started but the CRLs show that the confirmatory aspects of these trials should have already begun and that the timelines to completion should have been agreed upon prior to resubmission. “Regeneron is committed to working closely with the FDA and investigators to bring odronextamab to patients with R/R FL and R/R DLBCL as quickly as possible. Regeneron plans on sharing updates on enrollment and regulatory timelines later this year,” the company said in a statement. The drug was given priority review by the FDA last year and was also showing positive results. Of 128 patients assessed in a Phase II trial, 80% achieved an objective response while 73% had a complete response. Odronextamab in Phase II also showed the median duration of a response was 23 months, with the median time for a full response at 24 months. The average time for progression-free survival was 28 months. In August 2023, the European Medicines Agency started a regulatory review of the drug, which is still ongoing. The European Union has also given odronextamab orphan drug designation. Regeneron is not the only company to be slapped with CRLs recently. Earlier this month, the FDA rejected Viatris and Mapi Pharma’s formulation of glatiramer acetate—called GA Depot 40—for treating relapsing forms of multiple sclerosis. However, no details were provided as to why the letter was handed down. On the positive side of the regulatory ledger, the FDA last month accepted Regeneron and Sanofi’s supplemental BLA to expand Dupixent into chronic obstructive pulmonary disease. Tyler Patchen is a staff writer at BioSpace. You can reach him at tyler.patchen@biospace.com. Follow him on LinkedIn.

Mirum Pharmaceuticals’s LIVMARLI (maralixibat) oral solution is now available in the US for cholestatic pruritus in patients with PFIC. Credit: Mirum Pharmaceuticals / Business Wire. The US Food and Drug Administration (FDA) has approved Mirum Pharmaceuticals ’s LIVMARLI (maralixibat) oral solution to treat cholestatic pruritus. The medication is intended for patients aged five years and above with progressive familial intrahepatic cholestasis (PFIC). A once-daily, orally administered ileal bile acid transporter inhibitor, LIVMARLI is the sole FDA-approved treatment for PFIC. The approval is based on findings from the Phase III MARCH clinical trial in 93 PFIC patients. The randomised trial enrolled people with PFIC genetic types PFIC1, PFIC2, PFIC3, PFIC4 and PFIC6, along with people with unidentified mutational status. See Also: Terns scores FDA orphan designation for CML therapy FDA issues CRL to Mapi Pharma for GA Depot to treat RMS The FDA, the European Commission and Health Canada have also granted approval for LIVMARLI for the treatment of cholestatic pruritus in patients with Alagille syndrome in their respective regions. In addition to its current approvals, Mirum has filed a supplemental new drug application to the FDA. The aim is to introduce a higher concentration formulation of LIVMARLI, which was utilised in the Phase III MARCH study. This could expand the treatment’s label for younger PFIC patients later in 2024. A rare genetic disorder, PFIC results in progressive liver disease that can go on to cause liver failure. Mirum Pharmaceuticals CEO Chris Peetz stated: “LIVMARLI has the potential to have a transformational impact for patients with cholestatic pruritus associated with PFIC, and importantly, offers an option for those patients with the rarest of subtypes. “Thank you to the patients, families and clinicians whose study participation made this approval possible.” In September 2023, the company concluded the acquisition of the bile acid product portfolio of Travere Therapeutics . Mirum gained the rights and assets related to Cholbam (cholic acid) and Chenodal (chenodiol). Travere secured $210m from Mirum, with the potential to receive $235m in sales-based milestone payments.

Aside from Viatris’ approved Copaxone copycats, Sandoz markets its own MS generic dubbed Glatopa. Viatris likely just lost one of its top product debuts for 2024, thanks to an FDA rejection of its partner Mapi Pharma’s application for a new version of Teva’s multiple sclerosis (MS) drug Copaxone. Nevertheless, Viatris said the snub shouldn’t weigh on its revenue guidance—and it still expects to net upwards of $550 million from new drug launches this year. The FDA has issued a Complete Response Letter (CRL) slapping down Mapi’s approval bid for glatiramer acetate depot 40mg—a long-acting version of Viatris’ approved glatiramer acetate injection that can be taken just once a month, rather than multiple times a week or even daily. Viatris (by way of Mylan) originally scored a green light for two doses of its Copaxone generic back in Oct. 2017. The FDA approved a 40mg dose that needs to be administered three times a week, plus a 20mg version designed for daily use. Now, the company is working with Israel’s Mapi Pharma to try to get the long-acting product over the regulatory finish line. Mapi is a clinical-stage drugmaker focused on developing extended-release versions of branded drugs. Viatris and Mapi's long-acting glatiramer acetate depot 40, also known as GA Depot 40, isn't strictly a generic. Mapi claims to make "improved" versions of existing drugs. In its release, Viatris didn’t say why the FDA had rejected the long-acting version of the drug. The company is reviewing the FDA’s complete response with its partner to “determine next steps.” Viatris and Mapi voiced continued confidence in the potential viability of their once-a-month injection. The CRL won’t trigger a change in Viatris’ 2024 financial guidance or its new product revenue range of $450 million to $550 million, the company explained in a press release. In a recent earnings presentation, Viatris listed the new glatiramer acetate injection among its key new product launches in North America for 2024. The company is also banking on rollouts of copycats of drugs like the asthma medication Symbicort and the Type 2 diabetes therapy Victoza. Copaxone earned Teva around $320 million in North America last year, a 17% decline from the $387 million it generated in 2022. The drug hauled in another $231 million in Europe and $39 million in other international markets in 2023. For 2024, Teva expects Copaxone to bring home around $400 million globally. Aside from Viatris’ approved Copaxone copycats, Sandoz markets its own MS generic dubbed Glatopa, which launched in the summer of 2015 and boasts the distinction of being the first Copaxone generic approved in the U.S. While being eaten away by Sandoz and Mylan’s generics, Copaxone was still a key sales contributor for Teva back when the long-acting, 40mg version of the drug was denied new patent protections by the U.S. Court of Appeals in 2018. At the time, the court ruled that the once-a-month version of the branded drug wasn’t enough of an advance to warrant a slate of new intellectual property protections. As of late, Teva—now undergoing a revamp under new CEO Richard Francis—has largely been able to recover from its Copaxone revenue woes, thanks in large part to its steady roster of generics, plus newer brand-name medications like the Huntington’s disease drug Austedo and migraine med Ajovy. The new drugs generated $1.2 billion and $435 million last year respectively.