FDA red and green lights: January 2025

AstraZeneca got 2025 off to a good start, with the first US approval for its anti-TROP2 ADC, Datroway, and new indications for its more established products Enhertu and Calquence. However, the company will need to overcome recent hiccups if it’s to meet its goal of making $80bn in revenues by 2030.

The four oncology FDA green lights in January also included Amgen’s KRAS G12C inhibitor Lumakras in the new use of colorectal cancer, where Bristol Myers Squibb’s rival product, Krazati, has been available since June, albeit on an accelerated basis. Amgen had originally expected a decision in October, but the review period was extended by three months.

Meanwhile, things look less rosy for Atara, whose complete response letter for Ebvallo, on third-party manufacturing issues, was followed a few days later by a clinical hold. That company had been relying on a $60m approval milestone from its partner Pierre Fabre, without which its future looks uncertain.

$5bn drugs?

Astra expects Enhertu and Datroway each to become $5bn drugs, so both will be key to its lofty 2030 aim.

Enhertu is further down this road, with combined sales from Astra and Daiichi of $2.6bn in 2023. The latest expansion came in HER2-low and ultralow second-line breast cancer; however, there are questions about toxicity and the reliability of HER2 testing, which might hold back use.

And bigger tests are coming this year in first-line and periadjuvant breast cancer.

Datroway’s future looks less certain: although Astra now has its first US approval, in second-line ER-positive, HER2-negative breast cancer, the more important use of NSCLC took a blow when Astra pulled its second-line non-squamous filing last year, to focus on EGFR-mutated disease.

Still, the big opportunity is in first-line NSCLC, where various studies are ongoing including Avanzar, due to read out this year.

Astra also got the go ahead in January for its BTK inhibitor Calquence in first-line, transplant-ineligible mantle cell lymphoma, in combination with Rituxan and bendamustine. The green light, based on the Echo trial, also confirms Calquence’s 2017 accelerated approval in second-line mantle cell.

However, mantle cell is rare, with Astra estimating around 21,000 patients in the major economies worldwide. The decision looks unlikely to make much difference to Calquence sales, which totalled $2.3bn in the first nine months of 2024.

Lumakras expansion

Amgen has so far seen fairly lacklustre revenues for Lumakras, which first received accelerated approval in 2021 for second-line KRAS G12C-mutated NSCLC.

Now the drug also has full approval in second-line KRAS G12C-mutated colorectal cancer, in combination with Vectibix, based on the Codebreak-300 trial. The study showed improved progression-free survival versus investigator’s choice with the recommended 960mg Lumakras dose; while there was no benefit on overall survival, the study wasn’t powered to show this.

Meanwhile, Bristol’s Krazati got accelerated approval last year in second-line colorectal cancer, with the confirmatory Krystal-10 trial expected to yield data this year.

The companies seem to have colorectal largely to themselves, with the other big KRAS competitors apparently not pursuing this use, apart from Roche, whose phase 1 first-line Intrinsic trial includes cohorts testing its KRAS contender, divarasib.

In the first line Amgen is well ahead though, with the Codebreak-301 trial already ongoing.

Selected January 2025 US regulatory decisions in oncology

Source: OncologyPipeline.