CHMP recommends against Mirati’s KRAS rival, in favor of Pfizer’s RSV vaccine, other drugs

The European Medicines Agency’s human medicines committee (CHMP) recommended against conditional authorization for Mirati’s KRAS G12C inhibitor Krazati in non-small cell lung cancer this week, while giving the thumbs-up to 14 other drugs, including Pfizer’s RSV vaccine.

CHMP said on Friday that there were uncertainties about how well Krazati (adagrasib) worked, adding that “comprehensive data for this medicine were not yet available” and criteria for a conditional marketing authorization were unmet.

“The company could not show that Krazati fulfils an unmet need and could not justify making the medicine immediately available to patients while further data were still awaited,” the committee announced.

The target, KRAS, is a protein that regulates how cells grow and divide. Mutations can cause the protein to get stuck in the “on” position, triggering uncontrolled malignant cell growth. Krazati targets a mutation called G12C to lock the protein in “off” mode.

The drug won accelerated approval in the US in December to treat second-line patients with KRAS G12C-mutated locally advanced or metastatic NSCLC, becoming the second FDA-approved KRAS inhibitor behind Amgen’s rival Lumakras. That drug, also known as sotorasib, won conditional authorization in Europe last year, where it’s marketed as Lumykras.

Alan Sandler

Mirati’s CMO Alan Sandler defended Krazati’s benefit-risk profile in an email to Endpoints News on Friday, adding that CHMP’s decision was “based on the fact that an existing conditionally approved KRAS inhibitor is available.” Sandler said the company remains committed to its pursuit of conditional marketing authorization and intends to file a formal request for re-examination.

“Mirati disagrees with CHMP’s decision on the CMA and believes that there is an unmet need for patients living with cancer that Krazati can address,” Sandler said. “Differentiating characteristics of adagrasib, which are important considerations, include Krazati’s CNS mets activity, combinability with other agents including IO and unmatched efficacy.”

Positive recommendations 

Meanwhile, CHMP handed out positive recommendations to a handful of candidates, including Pfizer’s FDA-approved RSV vaccine Abrysvo. The shot was approved in the US in May to prevent lower respiratory tract disease caused by RSV in older adults 60 years and up, just a few weeks after GSK’s Arexvy won the FDA’s first approval for an RSV vaccine. CHMP’s recommendation covers older adults as well as infants in their first six months of life when administered to mothers during pregnancy.

CHMP referred to RSV as a “major public health interest,” adding that it’s a leading cause of pediatric hospitalization in Europe.

The committee also recommended an OK for BeiGene’s Novartis-partnered tislelizumab in unresectable, locally advanced or metastatic esophageal squamous cell carcinoma (ESCC) after chemotherapy. An approval here would mark the first ex-China indication for tislelizumab, approved for a number of cancers in China.

The FDA delayed its decision on tislelizumab in ESCC indefinitely last July, at which time BeiGene and Novartis disclosed that regulators were unable to complete an inspection due to Covid-related travel restrictions. Earlier this week, the partners said the FDA has completed its manufacturing inspection and the application is moving forward. If approved, the drug would be marketed as Tevimbra in Europe.

Among CHMP’s positive recommendations were ViiV’s Apretude (cabotegravir) for HIV-1 pre-exposure prophylaxis (PrEP), Merck’s Lyfnua (gefapixant) for refractory or unexplained chronic cough, and label expansions for a handful of drugs, including: a Keytruda combo in certain patients with gastric or a rare type of esophageal cancer; Bristol Myers Squibb’s Opdivo in certain melanoma patients; and Roche’s Evrysdi for certain infants under two months old with spinal muscular atrophy.

CHMP recommended updates to Moderna’s bivalent Covid-19 vaccine label which would extend its use to children 6 months and older, and to the general public regardless of their vaccination status.

While CHMP handed a positive recommendation to Ipsen’s Bylvay (odevixibat) to treat cholestatic pruritus in patients six months and older with Alagille syndrome, the company announced that a separate scientific committee of the EMA called the Committee for Orphan Medicinal Products (COMP) handed down a concurrent decision stripping the candidate of its orphan drug status, which may delay an approval decision.

“Ipsen plans to submit an appeal in respect of the COMP opinion,” the company said in a news release.

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