FDA Action Alert: Vanda, Basilea and J&J/Legend

After a hectic month, the FDA’s calendar appears to be easing up a bit. In the next two weeks, the regulator is facing just three major target action dates, including one potential CAR-T therapy approval that could push the class into earlier lines of treatment for multiple myeloma.

Read below for more.

Vanda Seeks Expansion of Fanapt into Bipolar Disorder

Vanda Pharmaceuticals is proposing its atypical antipsychotic Fanapt (iloperidone) as a treatment for bipolar I disorder. The FDA’s verdict is due on April 2.

In January, the Washington, D.C.-based biotech published Phase III data for iloperidone in the Journal of Clinical Psychiatry. The randomized, double-blinded and placebo-controlled study enrolled 414 adults with bipolar mania and demonstrated that iloperidone could induce significant symptom improvement within four weeks of treatment.

For instance, scores on the Young Mania Rating Scale, an 11-point clinical interview scale, were significantly better in the iloperidone group. The antipsychotic treatment likewise led to better scores on the Severity and Change subscores of the Clinical Global Impressions scale.

As for safety, treatment-emergent adverse events were more common in the iloperidone arm, though most were mild or moderate. Eighteen patients in the iloperidone group dropped out due to side effects, as opposed to 11 in the placebo arm. There were no deaths resulting from treatment toxicities.

Iloperidone is an atypical antipsychotic whose exact mechanism of action is still unknown, according to its label. Nevertheless, Vanda proposes that iloperidone exerts its effects by inhibiting the dopamine type 2 and serotonin type 2 pathways.

Iloperidone was approved in 2009 for the treatment of schizophrenia in adults. It comes with a boxed warning for a heightened risk of death in elderly patients suffering from dementia-related psychosis.

Basilea Awaits Approval for Antibiotic

By April 3, the FDA is expected to release its decision on Basilea Pharmaceutica’s New Drug Application (NDA) for its investigational antibiotic ceftobiprole for Staphylococcus aureus bacteremia (SAB), acute bacterial skin and skin structure infections (ABSSSI) and community-acquired bacterial pneumonia (CABP).

Designed to be administered intravenously, ceftobiprole is the active portion of the prodrug ceftobiprole medocaril. The drug candidate is a cephalosporin antibiotic that has shown rapid bacteria-killing properties with proven activity against the Gram-positive S. aureus, including methicillin-resistant strains, according to Basilea. Ceftobiprole has also shown potency against Gram-negative bacteria.

Basilea supported its NDA, which the FDA accepted in October 2023, with three Phase III studies. The first, dubbed ERADICATE, tested ceftobiprole in SAB patients.

Basilea published data from ERADICATE in September 2023, demonstrating that ceftobiprole was non-inferior to daptomycin in terms of the study’s primary endpoint of treatment success, which was a composite of survival, symptom improvement, bacteremia clearance, no new infection-related complications and no need for other antibiotics.

The NDA also included data from the Phase III TARGET study, which focused on ABSSSI, and another late-stage trial in CABP.

J&J, Legend Look to Push Carvykti into Earlier Lines of Multiple Myeloma Treatment

The FDA’s biggest decision in the coming week is for the CAR-T therapy Carvykti (ciltacabtagene autoleucel, cilta-cel), which its manufacturers Johnson & Johnson and Legend Biotech are proposing for the treatment of patients with relapsed or refractory multiple myeloma (RRMM) who have received at least one previous line of therapy.

The regulator’s decision is due on April 5, 2024.

Carvykti works by reprogramming a patient’s own T-cells, inducing the expression of a receptor that allows these immune cells to seek out and destroy cancer cells expressing the BCMA protein. Currently, Carvykti is indicated for patients who have undergone at least four prior lines of therapy, according to its label.

J&J and Legend are seeking an earlier-line approval for Carvykti on the back of their Phase III CARTITUDE-4 trial, which compared the CAR-T treatment to standard chemotherapy regimens, including pomalidomide-bortezomib-dexamethasone and daratumumab-pomalidomide-dexamethasone. The study showed that Carvykti reduced the risk of disease progression or death by 74% versus standard of care.

Earlier this month, the FDA’s Oncologic Drugs Advisory Committee voted 11–0 to back Carvykti’s approval as an earlier-line therapy. The unanimous support came despite what the FDA’s internal reviewers flagged as a “higher rate of early deaths” in patients treated with Carvykti.

The FDA has been erring on the side of caution when it comes to CAR-T therapies. In November 2023, the regulator launched a probe into the drug class, particularly regarding reports of secondary T-cell malignancies in treated patients. In January 2024, the FDA called for a class-wide boxed warning to alert prescribers and patients to such risks.

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