Oct. 18, 2024 - zolbetuximab-clzb (Vyloy) 

Astellas Pharma’s Vyloy has received FDA approval for use in combination with fluoropyrimidine- and platinum-containing chemotherapy for the first-line treatment of adults with locally advanced unresectable or metastatic human epidermal growth factor receptor 2 (HER2)-negative gastric or gastroesophageal junction adenocarcinoma whose tumors are claudin (CLDN) 18.2 positive as determined by an FDA-approved test. This claudin 18.2-directed cytolytic antibody is the first and only CLDN18.2-targeted therapy to receive FDA approval. Patients should be selected for treatment based on the presence of tumors that are CLDN18.2 positive (≥ 75% of tumor cells demonstrating moderate to strong membranous CLDN18 immunohistochemical staining). The FDA has also approved Roche Diagnostics’ Ventana CLDN18 RxDx Assay as a companion diagnostic device for identification of patients who may be eligible for treatment. Vyloy is supplied as a lyophilized powder in a single-dose vial for reconstitution and intravenous (IV) infusion. Dosing is based on body surface area (BSA) and following an initial loading dose, is given every two to three weeks until disease progression or unacceptable toxicity. Approval was based on two randomized, double-blind, placebo-controlled, phase 3 trials (SPOTLIGHT; n= 565; GLOW; n=507) that compared Vyloy plus chemotherapy to placebo plus chemotherapy; both trials demonstrated a significant reduction in the risk of disease progression or death (progression-free survival) compared with placebo (hazard ratio [HR], 0.75; p=0.0066 for SPOTLIGHT; HR, 0.69; p=0.0007 for GLOW). Vyloy was reviewed under the Priority Review pathway and received Fast Track and Orphan Drug designations; the review utilized Assessment Aid and the Real-Time Oncology Review (RTOR) pilot program. Vyloy is anticipated to be added to the National Comprehensive Cancer Network (NCCN) guidelines as a potential treatment option for the indicated patient population. Product is available with an average wholesale price (AWP) of $1,920 per single-dose vial.    

Nov. 8, 2024 - obecabtagene autoleucel (Aucatzyl)  

The FDA has approved Autolus’ cluster of differentiation (CD)19-directed genetically modified autologous T cell immunotherapy, Aucatzyl. The chimeric antigen receptor (CAR) T therapy is indicated for treatment of adults with relapsed or refractory B-cell precursor acute lymphoblastic leukemia (ALL). Aucatzyl, also known as obe-cel, is for IV use only and requires a lymphodepleting chemotherapy regimen of fludarabine/cyclophosphamide prior to infusion. The agent is approved as a cell suspension for infusion in three to five infusion bags that contain the total recommended dose of CD19 CAR-positive viable T cells. The cell suspension is given as a one-time treatment regimen consisting of a split dose infusion administered on day one and day 10 (+/- two days) with the dose administered being based on the patient’s bone marrow blast percentage (tumor burden) from a sample obtained within seven days prior to the start of lymphodepletion. Tocilizumab and emergency equipment are required to be available before the infusion and during the recovery period. Approval was based on the open-label, single-arm, phase 1b/2 FELIX clinical trial (n=112), which demonstrated that in the patients evaluable for efficacy (n=65), 63% achieved overall complete remission and 42% achieved complete remission within three months; for both of these efficacy endpoints the median duration was 14.1 months. Aucatzyl is expected to compete with other CD-19 directed genetically modified autologous T-cell immunotherapies that have similar indications: tisagenlecleucel (Kymriah) and brexucabtagene autoleucel (Tecartus). Aucatzyl was reviewed with Assessment Aid and received Orphan Drug and Regenerative Medicine Advanced Therapy designations. Although the product does not have a Risk Evaluation and Mitigation Strategy (REMS) program, boxed warnings for the agent include cytokine release syndrome, neurologic toxicities and secondary hematological malignancies. Autolus plans to communicate with current treatment centers for onboarding and initiation of scheduling of first patients for treatment. The AWP per one-time dose is $630,000. 

Nov. 13, 2024 - eladocagene exuparvovec-tneq (Kebilidi)  

PTC Therapeutics has received Accelerated Approval for eladocagene exuparvovec-tneq (Kebilidi), an adeno-associated virus (AAV) vector-based gene therapy indicated for the treatment of adult and pediatric patients with aromatic L-amino acid decarboxylase (AADC) deficiency. The Accelerated Approval is based on the change from baseline in gross motor milestones at 48 weeks post-treatment, and continued approval for this use may require demonstration of benefit in a confirmatory clinical trial. Approval marks the first FDA-approved gene therapy for treatment of AADC deficiency as well as the first gene therapy directly administered to the brain. Patients should be confirmed to have AADC deficiency due to biallelic mutations in the DOPA decarboxylase (DDC) gene. Variants in this gene lead to decreased AADC activity which results in lower production of dopamine and serotonin; this leads to decreased epinephrine and norepinephrine. Individuals with AADC deficiency experience severity disability and suffering early in life as the fatal condition results in developmental delays, movement problems, autonomic nervous system dysfunction and intellectual disabilities. Potential medical therapies for these patients include dopamine agonists, monoamine oxidase inhibitors (MAOIs), and pyridoxine. Kebilidi will be supplied as a suspension with a nominal concentration of 5.6 x10¹¹ vector genomes (vg)/mL in a single-dose vial that contains 2.8 x10¹¹ vg in an extractable volume of 0.5 mL. Kebilidi is administered via intraputaminal infusion only and requires brain imaging before the procedure for stereotactic planning and intraoperative navigation as well as surgical access through the skull bone/dura for administration. The dose is delivered as four infusions (two sites per putamen-anterior and posterior) for a total of 27 minutes per site during a single stereotactic surgery. The cannula that is used for administration should be FDA-authorized for intraparenchymal infusion, and the FDA has authorized ClearPoint Neuro’s SmartFlow Neuro Cannula for this purpose. Approval was based on an open-label, single-arm clinical study (n=13) that compared Kebilidi to a natural history cohort of untreated patients, and found Kebilidi resulted in improvements in gross motor function with eight of 12 (67%) treated patients achieving a new gross motor milestone at week 48. Intraputaminal administration of the gene therapy led to AADC enzyme expression followed by de novo dopamine synthesis. The gene therapy should be administered in a medical center specializing in stereotactic neurosurgery. Kebilidi was reviewed under Priority Review and received Orphan Drug designation. Launch preparations are underway with pricing to follow.