The FDA on Friday granted an accelerated approval to Amgen's Lumakras (sotorasib) as the first treatment for adults with KRAS G12C-mutated, locally advanced or metastatic non-small-cell lung cancer (NSCLC) following at least one prior systemic therapy. The FDA was expected to make a decision on the priority review filing by August 16. Amgen said it will charge a US list price of $17,900 per month for the drug, with analysts projecting it could eventually bring in more than $1 billion in annual sales.
"KRAS mutations have long been considered resistant to drug therapy, representing a true unmet need for patients with certain types of cancer," commented Richard Pazdur, acting director of the Office of Oncologic Diseases in the FDA's Center for Drug Evaluation and Research. He called the approval "a significant step towards a future where more patients will have a personalised treatment approach."
Lumakras, previously known as AMG 510, is being tested in the ongoing CodeBreaK 100 study of 733 adults with advanced solid tumours. The FDA approval is based on data from a Phase II cohort of the study involving 124 patients with KRAS G12C mutation-positive NSCLC who had disease progression after receiving an immunotherapy and/or chemotherapy. Results showed that 36% of patients given a once-daily 960-mg dose of the drug achieved a response, defined as ≥30% decrease in tumour. Lumakras also helped control disease in 81% of patients, with the median duration of response being 10 months.
Lead investigator Bob Li noted that most patients with KRAS-mutated tumours are initially treated with another targeted drug, such as Merck & Co.'s Keytruda (pembrolizumab), sometimes in combination with chemotherapy, although they have few options left when first-line treatment stops working. "For 40 years, we've not been able to crack this and…suddenly patients have a pill they can take once a day and for many patients the tumour will shrink," Li said.
Amgen estimates that about 13% of patients with non-squamous NSCLC in the US carry the KRAS G12C mutation. "Our sense is this is going to become more common in oncology," said R&D chief David Reese, adding that the company is also seeking regulatory approval of the drug in Europe, Japan and several other markets. Reese noted that Amgen is studying Lumakras in combination with other drugs as an initial treatment for NSCLC patients who have the KRAS mutation, as well as for other types of cancer.
Analysts at Cowen & Co. predict Lumakras will generate sales of $19 million this year and $138 million next, growing to more than $1 billion annually in 2026. However, Cowen analyst Yaron Werber suggested that in order to achieve those expectations, Amgen will have to show that the drug also works in the first-line setting, either in combination or sequentially with other medicines. "The chance for a much longer durability of effect, and hence much higher revenues, will depend on its ability to be combined – and there, the jury's still out," Werber said.
Meanwhile, Bernstein analyst Ronny Gal recently cautioned that the long-term value of Lumakras "is far from certain," because it may turn out that the drug does not add much benefit when combined with other treatments, while potentially better KRAS-targeted drugs are in development by other companies. "This makes us somewhat more concerned about the long-term outlook for [Amgen]," Gal said. For related analysis, see ViewPoints: Tepid growth at Amgen puts onus on KRAS.
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