FDA Updates for the Week of Nov. 20, 2023

FDA Approves First-in-Class Therapy for HR Positive Breast Cancer

The FDA has approved Truqap (capivasertib), along with Faslodex (fulvestrant), to treat patients with hormone receptor (HR)-positive, HER2-negative locally advanced or metastatic breast cancer. It is indicated for patients with one or more biomarker alterations, including PIK3CA, AKT1 or PTEN.

HR-positive breast cancer is the most common subtype, with more than 65% of tumors considered HR-positive and HER2-low or HER2-negative. The PI3K/AKT/PTEN signaling pathway participates in the regulation of cell growth, and alterations in these biomarkers closely related to tumor progression and resistance to standard therapies. Inhibiting the pathway has the potential to overcome resistance to anti-hormonal therapy and chemotherapy. Collectively, mutations in PIK3CA and AKT1 and alterations in PTEN occur frequently, affecting up to 50% of patients with advanced HR-positive breast cancer.

Developed by Astek Pharmaceuticals and partner AstraZeneca, Truqap is an AKT kinase inhibitor. An AstraZeneca spokesperson said Truqap will be available as soon as possible. A price is not available yet, but the spokesperson indicated that the price will reflects the clinical innovation and therapeutic benefit for patients and that patient assistance will be available.

The approval was based on results from the phase 3 CAPItello-291, which showed this combination reduced the risk of disease progression or death by 50% compared with Faslodex alone. Results were published earlier this year in The New England Journal of Medicine. Median progression-free survival was 7.3 months for the combination versus 3.1 months for Faslodex alone.

FDA to Hold Advisory Meeting for Abecma in Earlier Treatment of Multiple Myeloma

The FDA plans to hold a meeting of the Oncologic Drugs Advisory Committee to review data supporting Bristol Myers Squibb’s supplemental biologics license application (sBLA) for Abecma (idecabtagene vicleucel). BMS and partner 2seventy bio are seeking approval of Abecma to treat earlier lines of relapsed or refractory multiple myeloma (RRMM). The date of the ODAC meeting has not yet been set. As a result, a decision will not be made by the Prescription Drug User Fee Act (PDUFA) target action date of Dec. 16, 2023.

The companies said in a press release that they expect the advisory committee will review data related to the secondary endpoint of overall survival from the phase 3 KarMMa-3 study, which met its primary endpoint of improvement in progression-free survival (PFS) compared with standard regimens and reducing the risk of disease progression or death.

Abecma is currently approved for adult patients with triple-class exposed relapsed or refractory multiple myeloma after four or more prior lines of therapy. It is a B-cell maturation antigen (BCMA)-directed CAR-T cell immunotherapy. It binds to BCMA, a protein that is expressed on cancer cells in multiple myeloma.

The supplemental application was based on the phase 3 KarMMa-3 study, which enrolled 254 patients treated with Abecma and 132 patients treated with standard regimens; results were published earlier this year in The New England Journal of Medicine. At a median follow up of 18.6 months, treatment with Abecma results in a median progression-free survival of 13.3 months compared with 4.4 months for patients on standard care. This represents a 51% reduction in risk of disease progression or death with Abecma.

Janssen Submits Supplemental Application for Rybrevant in NSCLC

Janssen has submitted to the FDA a supplemental biologics license application (sBLA) for the approval of Rybrevant (amivantamab-vmjw) in combination with chemotherapy to treat patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) exon 19 deletions (ex19del) or L858R substitution. If approved, it would be indicated to treat patients after disease progression on or after Tagrisso (osimertinib).

Rybrevant is a fully-human bispecific antibody targeting EGFR and MET with immune cell-directing activity. It received accelerated approval by the FDA in May 2021 to treat adult patients with locally advanced or metastatic NSCLC with EGFR exon 20 insertion mutations. In August 2023, Janssen submitted an application for Rybrevant to be used as a first-line treatment with locally advanced or metastatic NSCLC with EGFR exon 20 insertion mutations.

The supplemental application for use after Tagrisso is based on data from the phase 3 MARIPOSA-2, which was recently presented at the European Society of Medical Oncology (ESMO) 2023 Congress in October 2023 and published in the Annals of Oncology. MARIPOSA-2 enrolled 657 patients in an open-label study that assessed Rybrevant (with and without lazertinib) and chemotherapy.