Nuvalent buy delivers new cancer approval for GSK

GSK has won FDA approval for Jideytro, a drug at the heart of its $10.6 billion acquisition of Nuvalent earlier this year – as a treatment for a form of lung cancer.

ROS1 inhibitor Jideytro (zidesamtinib) has been cleared by the US regulator as a second-line or later therapy for adults with locally advanced or metastatic ROS1-positive non-small cell lung cancer (NSCLC) who have already been treated with another drug in the class.

The drug has been specifically designed to work in ROS1-positive tumours that have developed resistance mutations, reducing the effectiveness of other drugs in the class like Pfizer's first-to-market Xalkori (crizotinib), Roche's Rozlytrek (entrectinib), and Bristol Myers Squibb's Augtyro (repotrectinib).

Its closest rival is arguably Nuvation's Ibtrozi (taletrectinib), which was approved by the FDA last year for ROS1-positive NSCLC, including first-line use, and has also been billed as a next-generation drug that can tackle tumours with resistance mutations.

The FDA approval of Jideytro comes on the back of the phase 1/2 ARROS-1 trial, in which Jideytro achieved an objective response rate (ORR) of 44%, with 69% of patients still responding to the treatment after 12 months follow-up. The drug was effective in patients with ROS1 mutations, as well as those whose cancer had spread to the brain.

"Despite advances in treatment, resistance mutations, disease progression in the brain and treatment-related adverse events continue to create challenges for patients," said Alexander Drilon of Memorial Sloan Kettering Cancer Centre in the US, one of the trial investigators.

"The responses observed in ARROS-1, including in heavily pre-treated patients, represent meaningful progress for people living with this disease."

GSK's lung cancer pathfinder product

Jideytro is GSK's first lung cancer therapy, and one of three for the disease added by the UK-headquartered pharma group through the takeover of Nuvalent, which was announced in June and closed last week.

ALK inhibitor called neladalkib is also under review at the FDA for pre-treated, advanced-stage ALK-positive NSCLC, with a decision due in November, while NVL-330 is in early-stage clinical development for HER2-altered NSCLC.

Analysts at Jefferies have previously suggested that the three drugs could generate sales of $5 billion to $7 billion a year at peak, which would be a massive boost to GSK as it chases down the target of building its annual revenues to £40 billion in 2031, from a little under £33 billion last year. They have suggested Jideytro's good tolerability profile could be a differentiator in the market.

Meanwhile, GSK is also developing another lung cancer candidate – B7-H3-targeted antibody-drug conjugate (ADC) risvutatug rezetecan (ris-rez) – which is licensed from Hansoh Pharma and recently had a positive phase 3 readout in relapsed small-cell lung cancer (SCLC).

Jideytro's approval has come nearly two months ahead of the FDA's action date for the application, and the company has said it intends to launch the product within the next few weeks. Pricing information has not yet been disclosed.