FDA delays colorectal cancer decision for Amgen’s Lumakras, a setback in race with Bristol Myers

The FDA has pushed back its de­ci­sion dead­line to move Am­gen’s KRAS in­hibitor Lumakras in­to metasta­t­ic col­orec­tal can­cer to Jan­u­ary, the com­pa­ny told End­points News.

The reg­u­la­tor was sup­posed to de­cide Thurs­day whether to ap­prove the drug in com­bi­na­tion with Am­gen’s EGFR drug Vectibix for chemore­frac­to­ry metasta­t­ic col­orec­tal can­cer pa­tients who have a KRAS G12C mu­ta­tion.

Af­ter End­points sent Am­gen ques­tions about the sta­tus of the re­view, the com­pa­ny said the new dead­line for ac­tion is three months from now, on Jan. 17, 2025. Am­gen said the de­lay was to “al­low ad­di­tion­al time for re­view of sup­ple­men­tal da­ta re­cent­ly sub­mit­ted to the agency.”

Lumakras is cur­rent­ly ap­proved un­der the ac­cel­er­at­ed path­way for non-small cell lung can­cer. An­oth­er KRAS in­hibitor, Bris­tol My­ers Squibb’s Kraza­ti, is al­so ap­proved un­der the ac­cel­er­at­ed path­way in both lung can­cer and col­orec­tal can­cer.

The col­orec­tal mar­ket is a large one, though KRAS G12C mu­ta­tions make up just 3% to 4% of metasta­t­ic cas­es. Can­cers of the colon and rec­tum are pro­ject­ed to make up 8% of all new can­cer di­ag­noses in 2024, ac­cord­ing to the Na­tion­al Can­cer In­sti­tute. That places those can­cers just be­hind breast, prostate and lung can­cers.

The FDA cleared Bris­tol My­ers’ Kraza­ti for use with Eli Lil­ly’s Er­bitux in June for pre­vi­ous­ly treat­ed lo­cal­ly ad­vanced or metasta­t­ic col­orec­tal can­cer pa­tients.

Am­gen ap­plied for ap­proval in metasta­t­ic col­orec­tal can­cer with re­sults from the Code­BreaK 300 study, which showed that a 960 mg dose of the drug re­sult­ed in a 30.2% re­sponse rate. How­ev­er, it didn’t im­prove over­all sur­vival, ac­cord­ing to da­ta pre­sent­ed in June, though Am­gen said the study wasn’t pow­ered to show a sta­tis­ti­cal­ly sig­nif­i­cant im­prove­ment in sur­vival.

Lumakras was the first KRAS in­hibitor to win reg­u­la­to­ry ap­proval in 2021. It marked a ma­jor med­ical break­through. Re­searchers have long known that KRAS mu­ta­tions dri­ve can­cer, but hadn’t been able to treat them in a tar­get­ed fash­ion. The ef­fi­ca­cy of the drugs, though, has been mod­est.

In lung can­cer, the FDA de­clined to con­vert Lumakras’ ac­cel­er­at­ed ap­proval to a full one in De­cem­ber, cit­ing con­cerns around the re­li­a­bil­i­ty of the piv­otal tri­al da­ta and not­ing that the me­di­an pro­gres­sion-free sur­vival ben­e­fit could be less than what Am­gen claimed — and po­ten­tial­ly as lit­tle as five days.

Com­mer­cial­ly, sales of Lumakras have been tepid, gen­er­at­ing $167 mil­lion for the first half of the year.

Roche is de­vel­op­ing its own KRAS in­hibitor di­vara­sib, which it is study­ing in a Phase 3 tri­al head-to-head against Kraza­ti and Lumakras in sec­ond-line lung can­cer and Phase 1/1b for col­orec­tal can­cer. Oth­er com­pa­nies, in­clud­ing Rev­o­lu­tion Med­i­cines, are de­vel­op­ing RAS in­hibitors that they hope can be more ef­fec­tive and go be­yond the sin­gle mu­ta­tion G12C, which could help treat more pa­tients.