Here is information on the latest US FDA approvals, the week of March 11 – March 15, 2024
Liso-cel for CLL/SLL, Tislelizumab for Esophageal SCC, Resmetirom for NASH, Maralixibat for Cholestatic Pruritus, Guselkumab for UC
Liso-cel for CLL/SLL
The FDA has approved lisocabtagene maraleucel (liso-cel; Breyanzi) for the treatment of adult patients with relapsed or refractory chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) who have previously received at least two prior lines of therapy, including a BTK inhibitor and a BCL-2 inhibitor. Liso-cel is a CAR T-cell therapy, which involves genetically modifying a patient’s T cells to express chimeric antigen receptors (CARs) that specifically target tumor antigens. The approval of lisocabtagene maraleucel was based on results from the phase 1/2 TRANSCEND CLL 004 study, which demonstrated a complete response rate of 20% among participants, with a median duration of response (DOR) that had not been reached at the time of the data cutoff. The study found that 100% of those achieving a complete response maintained their response at 12 months, with an 87.5% maintenance rate at 18 months. The overall response rate observed in the study was 45%, with a median DOR of 35.3 months.
The approval of lisocabtagene maraleucel was granted to Bristol Myers Squibb.
https://packageinserts.bms.com/pi/pi_breyanzi.pdf
Tislelizumab for Esophageal SCC
The FDA has approved tislelizumab-jsgr (Tevimbra) monotherapy for patients with unresectable or metastatic esophageal squamous cell carcinoma (ESCC) following prior systemic chemotherapy not including a PD-L1 inhibitor. ESCC, the most common histologic subtype of esophageal cancer, is aggressive in nature and options for those who have failed first-line treatments are limited. The approval was based on the phase 3 RATIONALE 302 trial, which enrolled 512 patients across 132 research sites in Europe, Asia, and North America. The trial demonstrated a significant improvement in overall survival for patients treated with tislelizumab compared to those receiving chemotherapy, with an overall survival of 8.6 months versus 6.3 months in the chemotherapy arm. This approval of tislelizumab-jsgr was granted to BeiGene.
Resmetirom for NASH
The FDA has approved resmetirom (Rezdiffra) for adults with noncirrhotic non-alcoholic steatohepatitis (NASH) with moderate to advanced fibrosis, alongside diet and exercise. This marks the first time a medication has been approved to directly address liver damage in patients with NASH who also have notable liver scarring. Resmetirom acts as a partial activator of a thyroid hormone receptor, reducing liver fat accumulation by activating this receptor in the liver. An estimated 6-8 million people in the US are affected by NASH with moderate-to-advanced liver scarring, and the disorder is often associated with comorbidities, such as high blood pressure and type 2 diabetes. The approval was based on the findings from a 54-month, randomized, double-blind placebo-controlled trial evaluating the safety and efficacy of resmetirom. The trial utilized a surrogate endpoint at month 12 to measure the extent of liver inflammation and scarring. At 12 months, liver biopsies revealed that a greater proportion of subjects treated with resmetirom achieved NASH resolution or an improvement in liver scarring compared to those receiving placebo. Resmetirom was granted approval under the FDA’s accelerated approval pathway, which requires a postapproval study to confirm the drug’s clinical benefit. The FDA granted the approval of resmetirom to Madrigal Pharmaceuticals.
Maralixibat for Cholestatic Pruritus
The FDA has approved maralixibat (Livmarli) oral solution for cholestatic pruritus in patients aged 5 years and above with progressive familial intrahepatic cholestasis (PFIC). Maralixibat is a once-daily, orally administered ileal bile acid transporter inhibitor. Maralixibat is already indicated for cholestatic pruritus in patients with Alagille syndrome. PFIC is a rare genetic disorder that leads to progressive liver disease and potentially liver failure. The approval of maralixibat was based on the outcomes of the Phase 3 MARCH clinical trial, which enrolled 93 patients with various genetic types of PFIC, demonstrating its efficacy in a broad range of PFIC patients. Additionally, the manufacturer Mirum Pharmaceuticals has submitted a supplemental new drug application for a higher concentration formulation of maralixibat, evaluated in the MARCH study, aiming to extend its use to younger PFIC patients.
https://files.mirumpharma.com/livmarli/livmarli-prescribinginformation.pdf
Guselkumab for UC
A supplemental biologics license application (sBLA) has been accepted for guselkumab (Tremfya) for the treatment of adults with moderate-to-severely active ulcerative colitis (UC). This submission is based on the results from the Phase 3 QUASAR program, which demonstrated a significantly greater percentage of patients achieving clinical remission at Week 44 with guselkumab compared to placebo. This program evaluated the efficacy and safety of guselkumab in individuals with moderately to severely active UC who had an inadequate response or intolerance to conventional therapy, prior biologics, and/or JAK inhibitors. Guselkumab is a dual-acting IL-23 inhibitor that not only blocks IL-23 but also binds to CD64, a receptor on cells that produce IL-23, making it a novel agent in the treatment of UC. Guselkumab was first approved in the U.S. in July 2017 for the treatment of adult patients with moderate-to-severe plaque psoriasis and also, in July 2020, for adults with active psoriatic arthritis. The approval of guselkumab was granted to Johnson & Johnson.