Novartis has gained FDA approval for its PI3K inhibitor Piqray for advanced breast cancer, bucking the trend for the drug class in solid tumour therapy.
The new drug is one of a clutch of 25 potential blockbusters Novartis hopes to launch in the next few years, and the first and only treatment to be approved by the FDA for patients with hormone receptor-positive, HER2- negative breast cancer with a PIK3CA mutation.
The approval is for Piqray (alpelisib formerly BYL719) alongside fulvestrant, a combination that almost doubled progression-free survival (PFS) compared to fulvestrant alone in the SOLAR-1 study. The duo improved median PFS to 11 months compared to 5.7 months with fulvestrant alone in this patient group, and more doubled the overall response rate to 38% versus 16%.
Its approval came on the same day as the FDA okay for Novartis’ gene therapy for rare disease spinal muscular atrophy (SMA) – Zolgensma – which is also predicted to be a future blockbuster.
After the SOLAR-1 data was announced last year, analysts at Jefferies said the drug could become a $1.5bn blockbuster, as it is the first drug in the PI3K inhibitor class whose benefits have outweighed its toxicities in breast cancer.
Three PI3K inhibitors have been approved for blood cancers – namely Gilead Sciences’ Zydelig (idelalisib), Bayer’s Aliqopa (copanlisib) and Verastem’s Copiktra (duvelisib) – but so far they have been unable to make the transition to solid tumour treatment.
Rival Swiss pharma Roche was also developing a PI3K inhibitor for breast cancer – called taselisib – but abandoned the project last year after disappointing results in the phase 3 SANDPIPER trial. It’s still working on drug candidates in this area, however.
PIK3CA is the most commonly mutated gene in HR+/HER2- breast cancer, seen in approximately 40% of patients, and tends to make them less responsive to standard treatment with hormone-based therapies.
In another milestone, the new drug application for the PI3K inhibitor is the first to be approved via the FDA’s new Real-Time Oncology Review (RTOT) pilot programme, which aims to bring promising new drugs to patients as quickly as possible allowing the FDA to review data earlier.
“Today’s approval is expected to change the way we practice medicine in advanced breast cancer,” said Fabrice André of the Institut Gustave Roussy in France, who led the SOLAR-1 trial.
“For the first time, physicians can test for PIK3CA biomarkers and develop a treatment plan based on the genomic profile of a patient’s cancer,” he added. A companion diagnostic developed by Qiagen to test for the mutation has also been approved by the FDA.
Trials are also in play comparing alpelisib and fulvestrant to chemotherapy as maintenance therapy in PIK3CA-mutated breast cancer, as well as oropharyngeal and head and neck cancer.