FDA Approves Major Safety and Indication Updates for Sarepta’s ELEVIDYS Gene Therapy
Sarepta Therapeutics announced that the U.S. Food and Drug Administration (FDA) has approved significant updates to the prescribing information for its Duchenne muscular dystrophy (DMD) gene therapy, ELEVIDYS (delandistrogene moxeparvovec-rokl). This regulatory action follows reports of serious adverse events, including fatal cases of acute liver failure in non-ambulatory patients treated with the therapy. The updated label now includes a Boxed Warning, the FDA’s most prominent safety alert, detailing the risk of acute serious liver injury and acute liver failure.
Crucially, the approved indication for ELEVIDYS has been revised and is now restricted to ambulatory patients four years of age and older with a confirmed DMD gene mutation, removing the previous allowance for non-ambulatory patients. Furthermore, the label introduces a new contraindication for patients with deletions in exon 8 and/or exon 9 of the DMD gene. To mitigate safety risks, the FDA approved expanded prescriber guidance, which includes a modified pre- and post-infusion systemic corticosteroid regimen and enhanced safety monitoring, specifically requiring weekly liver function tests for three months post-infusion.
A new warning also addresses the potential for increased susceptibility to severe infections due to necessary immunosuppression. Sarepta has stated its intention to immediately initiate a study of an enhanced sirolimus immunosuppressive regimen to address the risk of liver injury, to potentially resume dosing for non-ambulatory patients pending FDA approval.
Merck to Acquire Cidara Therapeutics for $9.2 Billion to Secure Late-Phase, Long-Acting Flu Antiviral CD388
Merck has announced a definitive agreement to acquire Cidara Therapeutics, Inc., in a significant all-cash transaction valued at approximately $9.2 billion. The deal, which will see Merck pay $221.50 per share for all of Cidara’s outstanding stock, is a key component of Merck’s strategy to strengthen its respiratory pipeline and offset future patent expirations of key products, such as KEYTRUDA. The centerpiece of the acquisition is CD388, a potentially first-in-class, long-acting antiviral agent currently in a Phase 3 study (ANCHOR trial) for the prevention of symptomatic influenza A and B.
CD388 is a novel drug-Fc conjugate (DFC) designed to provide season-long, single-dose protection against influenza, particularly targeting high-risk individuals, such as the elderly and immunocompromised, whose immune response to traditional vaccines may be suboptimal. The drug, which functions as a direct viral inhibitor rather than a vaccine, previously received FDA Breakthrough Therapy designation based on strong Phase 2b data that showed up to 76% prevention efficacy over 24 weeks. Merck CEO Robert M. Davis emphasized that CD388 is expected to be a significant growth driver for the company throughout the next decade. The transaction, approved by the boards of both companies, is structured as a tender offer and is projected to close in the first quarter of 2026.
BMS and Johnson and Johnson Discontinue Phase 3 Trial for FXIa Inhibitor Milvexian in Acute Coronary Syndrome
Bristol Myers Squibb (BMS) and Johnson & Johnson (J&J) have announced the discontinuation of the Phase 3 Librexia ACS trial, which was evaluating their investigational oral Factor XIa (FXIa) inhibitor, milvexian, for patients who recently experienced an Acute Coronary Syndrome (ACS) event. This decision follows a pre-planned interim analysis conducted by the Independent Data Monitoring Committee (IDMC). The study concluded that the trial was unlikely to meet its primary efficacy endpoint when milvexian was added to the standard antiplatelet therapy.
Milvexian is a crucial asset within the broader FXIa inhibitor class, which is being developed as a next-generation antithrombotic therapy hypothesized to provide the benefits of reduced thrombotic events with a lower risk of bleeding compared to current Factor Xa inhibitors, such as ELIQUIS and XARELTO. While the trial failed on its primary efficacy objective, the companies noted that no new safety concerns were identified, and the safety profile remained consistent with previous studies.
Crucially, the IDMC recommended that the two other pivotal Phase 3 studies in the comprehensive Librexia program, Librexia AF (for atrial fibrillation) and Librexia STROKE (for secondary stroke prevention), should proceed as planned. Topline results for these remaining high-stakes trials are still expected in 2026. Despite this significant setback in the ACS indication, the collaboration partners maintain their commitment to the overall Librexia program and the potential of milvexian in other high-risk thrombotic conditions.
KOMZIFTI (ziftomenib) Gains FDA Approval as First Once-Daily Targeted Oral Therapy for R/R NPM1-Mutated AML
Kura Oncology and Kyowa Kirin have announced that the U.S. Food and Drug Administration (FDA) has granted full approval for KOMZIFTI (ziftomenib). This landmark approval establishes KOMZIFTI as the first and only once-daily, oral, targeted therapy for adult patients with relapsed or refractory (R/R) acute myeloid leukemia (AML) harboring a susceptible NPM1 mutation, a genetic alteration present in approximately 30% of all AML cases and associated with a historically poor prognosis upon relapse.
KOMZIFTI is a selective menin inhibitor that works by disrupting the oncogenic interaction between the menin protein and mutant NPM1, thereby promoting the differentiation of leukemic blasts back into healthy cells. The approval was granted ahead of the PDUFA target action date and is based on robust data from the pivotal Phase 2 KOMET-001 trial. In this study of heavily pretreated patients, KOMZIFTI demonstrated clinically meaningful efficacy, achieving a complete remission (CR) plus CR with partial hematologic recovery (CRh) rate of 21.4%. Notably, the therapy’s profile is highlighted by its once-daily oral administration and a manageable safety profile, including no Boxed Warning for QTc prolongation, a significant advantage for this vulnerable patient population often receiving multiple concurrent medications.
This approval addresses a critical unmet need for R/R NPM1-mutated AML, particularly for older patients who may be ineligible for intensive chemotherapy or transplant. Kura Oncology and Kyowa Kirin are now prepared for the U.S. launch, marking a major advancement in moving AML treatment toward precise, mutation-specific targeted therapies.
Novartis’s KLU156 (GanLum) Meets Phase III Goal, Posing Major New Threat to Drug-Resistant Malaria
Novartis, in collaboration with Medicines for Malaria Venture (MMV), has announced positive topline results from the Phase III KALUMA trial evaluating its investigational next-generation malaria treatment, KLU156 (GanLum). The study successfully met its primary endpoint, demonstrating non-inferiority to the current standard of care, Coartem (artemether-lumefantrine), for treating acute, uncomplicated Plasmodium falciparum malaria.
GanLum, a combination of the novel non-artemisinin compound ganaplacide and a new formulation of lumefantrine, achieved a high PCR-corrected cure rate of 97.4% at Day 29 (using the conservative estimand framework), compared to 94.0% for the standard of care. Under conventional per-protocol analysis, GanLum’s cure rate reached 99.2%. The trial, which enrolled over 1,600 adults and children across 12 African countries, confirmed the drug’s efficacy in a high-burden setting where antimalarial drug resistance is a growing threat.
Crucially, GanLum is positioned as a critical new tool in the fight against the escalating resistance to antimalarials. Its key component, ganaplacide, has an entirely new mechanism of action, targeting the parasite’s internal protein transport systems—a method distinct from the current gold standard, ACTs. Additional analyses confirmed that GanLum remains highly effective against mutant malaria parasites linked to partial drug resistance. Furthermore, the treatment demonstrated rapid activity against mature gametocytes, the sexual stage of the parasite responsible for human-to-mosquito transmission, offering the potential to reduce disease spread. If approved, GanLum would represent the first major innovation in malaria treatment since the introduction of ACTs more than 25 years ago.
