Lilly's Cyramza, after split decision from FDA advisers, wins first-line lung cancer nod

Eli Lilly has won FDA approval for Cyramza in combination with Roche’s Tarceva as a first-line treatment for EGFR-mutated non-small cell lung cancer. (Eli Lilly/LinkedIn)

When an FDA advisory panel narrowly backed Eli Lilly’s Cyramza for use in newly diagnosed non-small cell lung cancer (NSCLC), a final approval didn’t seem so certain. Now, the company can breathe a sigh of relief, as the agency has decided to follow the experts’ recommendation.

Friday, the FDA greenlighted Cyramza in combination with Roche’s Tarceva for previously untreated NSCLC with EGFR mutations.

The decision was based on the phase 3 Relay trial, which showed the pairing could cut the risk of disease progression or death by 40% over Tarceva alone. Patients on the combo lived a median 19.4 months without disease progressing, compared with 12.4 months for those on Tarceva plus placebo.

That kind of showing is by itself encouraging. But during an FDA oncology advisory committee meeting in February, experts pointed to AstraZeneca’s rival drug Tagrisso and the fact that the blockbuster med already had data demonstrating it could extend patients’ lives, the gold standard for judging an oncology drug’s efficacy.

A relatively high number of grade 3 or above treatment-related side effects, such as hypertension, infections and bleeding, raised concerns among the experts, leading to a final vote of 6 to 5 in favor of Cyramza’s approval.

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In its own clinical trial, Tagrisso helped newly diagnosed EGFR-mutated NSCLC patients lived a median 38.6 months, nearly seven months longer than patients lived on either one of first-generation EGFR TKIs, namely Tarceva and AZ’s own Iressa. That translated into a 20% reduction in the risk of death. As for tumor progression, Tagrisso cut that risk by 54% with median progression-free survival of 18.9 months, versus 10.2 months for the older drugs.

To hear Lilly Oncology’s late-phase development chief Maura Dickler tell it, the approval for Cyramza-Tarceva is about offering another choice for treatment. “We believe doctors should have options when they’re discussing therapy with patients,” she recently told FiercePharma, adding that the seven-month progression-free advantage the regimen has delivered is “clinically meaningful.”

Dickler also pointed to the advisory committee’s discussion around the option for sequencing, noting that patients who start with Cyramza-Tarceva in the first line can go on to get Tagrisso if needed.

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To be fair, Tagrisso also won its FDA clearance with data on disease progression but not on life extension. And if Tagrisso is any indication, overall survival data could take years to arrive. “Patients in that front-line setting who get an EGFR-targeted therapy do exceptionally well,” Dickler said.

At the point of the data cutoff, only 26% of patients had died in the treatment arm, far from the 300 deaths necessary for a planned survival analysis, according to Lilly. But Dickler acknowledged the consensus at the FDA advisory meeting was that the Relay study, which enrolled 449 patients altogether, is likely not large enough to yield a clear overall survival benefit.

Now, it’s up to Lilly to go after Tagrisso, which has established itself as the leader in the EGFR arena. As the top-selling drug in AZ’s portfolio, Tagrisso grew sales by 71% in 2019 to $3.19 billion, mainly thanks to continued demand in the front-line NSCLC setting. In comparison, sales of Cyramza, which is also approved in other cancer types, increased by 13% year over year to $925 million.