Amgen picks up key colorectal cancer okay for KRAS drug

Amgen's first-to-market KRAS inhibitor Lumakras has so far failed to live up to once-lofty sales expectations, but a new FDA approval could lend momentum to its growth.

The US regulator has cleared Lumakras (sotorasib) in combination with Amgen's anti-EGFR antibody Vectibix (panitumumab) for adults with KRAS G12C-mutated metastatic colorectal cancer (CRC) who have been previously treated with chemotherapy.

The green light comes on the strength of data from the phase 3 CodeBreaK 300 study, which showed that Lumakras plus Vectibix was the first targeted treatment combination to show superior progression-free survival (PFS) compared to the standard-of-care for this chemorefractory CRC patient population.

It is the second approved indication for Lumakras, which has been used since 2021 as a second-line treatment for KRAS G12C-mutated non-small cell lung cancer (NSCLC), and the go-ahead after a three-month extension in the FDA's review time for the application.

Crucially, it will allow Lumakras to compete head-to-head in CRC with its main KRAS inhibitor rival – Bristol Myers Squibb's Krazati (adagrasib) – which claimed accelerated approval in combination with EGFR antibody Erbitux (cetuximab) for a similar CRC patient population last year.

It also follows disappointing results from a confirmatory trial of Krazati in its current NSCLC indication, designed to convert its earlier accelerated registration into a full approval. The FDA declined to do so in 2023, on the grounds that the CodeBreak 200 data was not strong enough to show conclusively that Lumakras improved PFS.

The study showed a 34% reduction in PFS compared to docetaxel chemotherapy in patients previously treated with at least one platinum-based chemotherapy and checkpoint inhibitor, a statistically significant difference. However, the FDA said it was unconvinced by the result as the trial was small, had problems with its design, and was prone to bias.

The regulator has asked for a new study to be completed by 2028, otherwise Lumakras could lose its NSCLC indication.

Lumakras made $280 million in sales in 2023 and another $236 million in the first nine months of last year – falling short of the upwards momentum needed to fulfil Amgen's hopes of blockbuster sales – but the new CRC indication could kickstart growth.

Amgen's head of R&D, Jay Bradner, said CRC is the third leading cause of cancer-related deaths in the US, and fewer than one in five people diagnosed with metastatic disease survive beyond five years after diagnosis. KRAS mutations are among the most common genetic alterations in CRC, with the KRAS G12C mutation present in approximately 3% to 5% of cases.

"Lumakras plus Vectibix offers a targeted, biomarker-driven combination therapy that helps delay disease progression more effectively than the investigated standard of care," continued Bradner.

"This new option validates our combination approach to improve outcomes for patients living with advanced KRAS G12C-mutated metastatic colorectal cancer."