FDA Drug Approval Decisions Expected in April 2024

The Prescription Drug User Fee Act (PDUFA) date refers to the deadline set by the US Food and Drug Administration (FDA) for reviewing a New Drug Application (NDA) or Biologics License Application (BLA) and making a final decision on marketing approval. The typical period for review is 10 months after the drug application has been accepted by the Agency. For drugs that have Priority Review, the review period is reduced to 6 months from the time of application acceptance.

Ceftobiprole for the Treatment of Serious Bacterial Infections

PDUFA date: April 3, 2024

Ceftobiprole is a broad spectrum cephalosporin antibiotic for intravenous administration. The drug has been shown to have rapid bactericidal activity against Gram positive bacteria such as Staphylococcus aureus, including methicillin-resistant strains (MRSA), and Gram negative bacteria. Basilea is seeking approval for 3 indications: S. aureus bacteremia (SAB), including right-sided infective endocarditis, acute bacterial skin and skin structure infections (ABSSSI) and community-acquired bacterial pneumonia (CABP). The application is supported by data from three phase 3 studies: ERADICATE (ClinicalTrials.gov Identifier: NCT03138733), TARGET (ClinicalTrials.gov Identifier: NCT03137173), and a phase 3 study in CABP (ClinicalTrials.gov Identifier: NCT00326287). Findings from these trials supported the effectiveness of ceftobiprole in the treatment of SAB, ABSSSI, and CABP vs a comparator antibiotic.

SPN-830 for Continuous Treatment of Motor Fluctuations in Parkinson Disease

PDUFA date: April 5, 2024

SPN-830 is an apomorphine infusion device that provides continuous treatment of motor fluctuations (off episodes) in adults with Parkinson disease. The drug/device combo had originally been submitted to the FDA for review in September 2020. The application included data from the phase 3 TOLEDO study (ClinicalTrials.gov Identifier: NCT02006121) and a supportive open-label study (ClinicalTrials.gov Identifier: NCT02339064). Results from TOLEDO showed that SPN-830 was associated with a statistically significant reduction in mean daily off time compared with placebo. The FDA subsequently issued a Refuse to File letter, and then a Complete Response Letter, which required Supernus to provide additional analysis for review. Apomorphine, a non-ergoline dopamine agonist, is currently available as a solution for subcutaneous injection and as a sublingual film.

N-803 plus BCG for High-Risk Non-Muscle-Invasive Bladder Cancer

PDUFA date: April 23, 2024

N-803 (Anktiva^®) is an interleukin-15 (IL-15) superagonist complex consisting of an IL-15 mutant (IL-15N72D) bound to an IL-15 receptor α/IgG1 Fc fusion protein. The investigational agent is being reviewed in combination with Bacillus Calmette-Guérin (BCG) for the treatment of BCG-unresponsive non-muscle-invasive bladder cancer (NMIBC) carcinoma in situ (CIS) with or without Ta or T1 disease. The BLA is supported by data from the phase 2/3, open-label QUILT-3.032 study (ClinicalTrials.gov Identifier: NCT03022825). Findings showed 71% of patients with BCG-unresponsive NMIBC CIS and papillary disease treated with intravesical BCG plus N-803 achieved a complete response (primary endpoint), with median duration of response of 26.6 months. Among patients with CR, the Kaplan-Meier-estimated probability of avoiding cystectomy and of bladder cancer-specific survival was 89.2% and 100%, respectively, at 24 months. 

Tovorafenib for Relapsed or Progressive Pediatric Low-Grade Glioma

PDUFA date: April 30, 2024

Tovorafenib is an oral, brain-penetrant, highly-selective type II RAF kinase inhibitor designed to target a key enzyme in the MAPK signaling pathway. It is being reviewed for the treatment of relapsed or progressive pediatric low-grade glioma (pLGG). The NDA includes efficacy and safety data from the open-label, phase 2 FIREFLY-1 study (ClinicalTrials.gov Identifier: NCT04775485), which included 77 patients 6 months to 25 years of age with relapsed or progressive pLGG. Findings showed that among the 69 evaluable patients, the overall response rate (by Response Assessment for Neuro-Oncology High Grade Glioma criteria) was 67%, with median duration of response of 16.6 months. Tovorafenib was granted Rare Pediatric Disease Designation for relapsed or progressive pLGG.

Mavorixafor for the Treatment of WHIM Syndrome

PDUFA date: April 30, 2024

Mavorixafor is an investigational oral small-molecule antagonist of the CXCR4 receptor. It is being reviewed for the treatment of patients 12 years of age and older with WHIM (warts, hypogammaglobulinemia, infections, and myelokathexis) syndrome, a rare, primary immunodeficiency. The application includes data from the phase 3, double-blind, placebo-controlled 4WHIM study (ClinicalTrials.gov Identifier: NCT03995108), which evaluated oral, once-daily mavorixafor vs placebo in patients with genetically confirmed WHIM syndrome (N=31). Findings showed mavorixafor was associated with statistically significant and clinically relevant longer times above threshold levels for both absolute neutrophil (P <.0001) and absolute lymphocyte counts (P <.0001) compared with placebo. Treatment with mavorixafor also resulted in reductions in the rate, severity, and duration of infections vs placebo.