FDA Gears Up for Key Approval Decisions in Q4 2024
核心洞察
The FDA is set to decide on dasiglucagon for congenital hyperinsulinism (搜索), with a PDUFA date of October 8, potentially benefiting pediatric patients.
Nivolumab-based regimens for resectable NSCLC (搜索) are under review, supported by Phase 3 data showing a 42% reduction in disease recurrence, with a PDUFA date of October 8.
Acoramidis for transthyretin amyloid cardiomyopathy (搜索) shows promise, with Phase 3 results indicating statistically significant improvements and a PDUFA date of November 29.
The final quarter of 2024 promises several significant FDA approval decisions that could reshape treatment paradigms across a range of conditions, from rare metabolic disorders to prevalent cancers and cardiovascular diseases. Here's a closer look at some of the key drugs and biologics under review.
Dasiglucagon for Congenital Hyperinsulinism
With a PDUFA date of October 8, dasiglucagon, a ready-to-use glucagon analog, is being evaluated for the prevention and treatment of hypoglycemia in pediatric patients (7 days and older) with congenital hyperinsulinism (搜索) (CHI). CHI is a rare genetic disease characterized by persistent hypoglycemia due to insulin overproduction. The NDA is supported by data from two Phase 3 trials and an ongoing long-term extension study.
The FDA is conducting its review in two parts, with the initial decision focusing on use for up to 3 weeks of dosing. This approval could provide a much-needed option for managing hypoglycemia in this vulnerable population.
Nivolumab-Based Regimen for Resectable NSCLC
Also with an October 8 PDUFA date, the FDA is considering a supplemental Biologics License Application (sBLA) for neoadjuvant nivolumab with chemotherapy, followed by surgery and adjuvant nivolumab, for perioperative treatment of resectable stage IIA to IIIB non-small cell lung cancer (NSCLC (搜索)). The application is backed by data from the Phase 3 CheckMate-77T trial, a randomized, double-blind, placebo-controlled study.
At a median follow-up of 25.4 months, nivolumab-based treatment reduced the risk of disease recurrence, progression, or death by 42% (event-free survival hazard ratio, 0.58; 97.36% CI, 0.42-0.81; P = .00025). This regimen could represent a significant advancement in the treatment of resectable NSCLC (搜索).
Oclaiz (CAM2029) for Acromegaly
With a PDUFA date of October 21, Oclaiz™ (CAM2029), an investigational once-monthly octreotide subcutaneous depot, is under review for the treatment of patients with acromegaly (搜索). The NDA is supported by data from seven clinical studies, including two Phase 3 studies (ACROINNOVA 1 and ACROINNOVA 2).
The ACROINNOVA 1 trial, a 24-week, randomized, double-blind, placebo-controlled study, included 72 adult patients with acromegaly (搜索) on stable treatment with standard of care. Findings showed 72.2% of patients treated with Oclaiz had a biochemical response compared with 37.5% of those who received placebo (primary endpoint; mean insulin-like growth factor [IGF-1] ≤upper limit of normal [ULN] at week 22 and 24; P =.0018).
Sulopenem Etzadroxil/Probenecid for Uncomplicated UTI
The FDA is reviewing the resubmitted NDA for sulopenem etzadroxil/probenecid for the treatment of uncomplicated urinary tract infections (搜索) (UTIs) in adult women, with a PDUFA date of October 25. Sulopenem etzadroxil is an investigational oral penem anti-infective combined with probenecid in a bilayer tablet. The resubmission includes data from the Phase 3 REASSURE trial.
Findings showed treatment with sulopenem/probenecid was statistically superior to amoxicillin/clavulanate. Overall success, defined as clinical and microbiologic success, was achieved by 61.7% of the sulopenem/probenecid group and 55% of the amoxicillin/clavulanate group.
DFD-29 for Rosacea
DFD-29, an investigational formulation of minocycline hydrochloride in a modified-release capsule, is under review for treating inflammatory lesions and erythema associated with rosacea (搜索). The NDA includes data from two Phase 3 trials (MVOR-1 and MVOR-2), assessing its efficacy and safety against doxycycline 40mg and placebo in adults with moderate to severe papulopustular rosacea. The PDUFA date is November 4, 2024.
Results indicated DFD-29's superiority over doxycycline 40mg and placebo, based on the proportion of patients achieving Investigator’s Global Assessment treatment success and total inflammatory lesion count reduction.
Eladocagene Exuparvovec for AADC Deficiency
With a PDUFA date of November 13, eladocagene exuparvovec, a one-time gene replacement therapy, is under review for aromatic L-amino acid decarboxylase (AADC) deficiency, a rare genetic disorder. The therapy is designed to restore dopamine production by delivering the AADC enzyme directly into the putamen.
The FDA granted Priority Review of the BLA, which includes efficacy and safety data from clinical trials and compassionate use programs. Findings showed neurological improvements in patients with AADC, with long-term data demonstrating sustained improvements in motor and cognitive function over five years.
Inavolisib for PIK3CA-Mutated HR-Positive Breast Cancer
The FDA is reviewing inavolisib in combination with palbociclib and fulvestrant for PIK3CA-mutated, hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2 (搜索))-negative, locally advanced or metastatic breast cancer (搜索), following recurrence on or within 12 months of completing adjuvant endocrine treatment. The PDUFA date is November 27, 2024.
Inavolisib is a selective inhibitor of the PI3K alpha isoform. Phase 3 INAVO120 study results showed the inavolisib-based regimen reduced the risk of disease progression or death by 57% compared with palbociclib and fulvestrant alone (hazard ratio, 0.43; 95% CI, 0.32-0.59; P < .0001).
Acoramidis for Transthyretin Amyloid Cardiomyopathy
Acoramidis, an orally-administered small molecule designed to stabilize tetrameric transthyretin, has a PDUFA date of November 29. The NDA submission includes data from the Phase 3 ATTRibute-CM trial, which evaluated the efficacy and safety of acoramidis in 632 adults with symptomatic transthyretin amyloid cardiomyopathy (搜索).
Results showed a statistically significant improvement with acoramidis compared with placebo, corresponding to a win ratio of 1.8 (95% CI, 1.4-2.2; P < .0001).
Zanidatamab for HER2-Amplified Biliary Tract Cancer
The FDA is reviewing the BLA for zanidatamab, a bispecific antibody that binds to two non-overlapping extracellular epitopes of the HER2 (搜索) receptor, in patients with previously treated, unresectable, locally advanced, or metastatic HER2-positive biliary tract cancer (搜索) (BTC). The PDUFA date is November 29, 2024.
The BLA is supported by data from cohort 1 of the Phase 2b HERIZON-BTC-01 trial, which evaluated zanidatamab monotherapy in 87 patients with HER2 (搜索)-amplified BTC with disease progression on previous gemcitabine-based therapy. Results showed an objective response rate of 41.3% (95% CI, 30.4-52.8).