Pfizer's Xalkori follow-up, which smoked the older drug in 1st-line patients, scores double win at the FDA
Despite being the first to market in ALK-positive non-small cell lung cancer, Pfizer’s Xalkori languished on the shelf as other competitors outpaced it. Now, after Pfizer’s follow-up drug absolutely smoked Xalkori in first-line patients, the FDA is taking notice.
In one fell swoop, the agency approved Lorbrena as a first-line treatment for patients with anaplastic lymphoma kinase (ALK)-positive NSCLC and extended the drug’s 2018 accelerated approval to a full approval, Pfizer announced on Wednesday.
The pharma’s stock $PFE jumped about 2.6% from Tuesday to Wednesday, hovering around $34.56 per share on Thursday morning.
Lorbrena got an accelerated OK three years ago as a second-line treatment for ALK-positive NSCLC. Specifically, patients must have tried Xalkori and at least one other ALK-inhibitor — either Roche’s Alecensa or Novartis’ Zykadia — before being prescribed Lorbrena. If those medications didn’t stop disease progression, they could give Lorbrena a try.
The FDA’s decision to extend the approval was based on results from the open-label Phase III CROWN trial, in which Lorbrena lowered the relative risk of disease progression by 72% in a head-to-head matchup with Xalkori in NSCLC patients who had received no prior treatment — the primary endpoint, according to Pfizer.
In total, 296 volunteers with untreated ALK-positive NSCLC were randomized 1:1 to receive either Lorbrena or Xalkori. Progression-free survival was evaluated based on a blinded independent central review. Of 149 patients in the Lorbrena arm, 17 had measurable brain metastases at baseline — a frequent site for disease progression in ALK-positive NSCLC. Up to 40% of patients with the disease are found to have brain metastases at initial diagnosis, according to Pfizer. In the Xalkori arm, 13 of 147 patients had brain metastases at baseline.
Among those patients, Pfizer boasted an 89% intracranial objective response rate in the Lorbrena arm, versus 23% in the Xalkori arm. The intracranial duration of response was 12 months or longer in 79% of the Lorbrena patients, compared to none of the Xalkori patients, according to the data.
“The CROWN data have shown LORBRENA can significantly improve outcomes in the first-line treatment of ALK-positive non-small cell lung cancer, including those that present with brain metastases,” said Benjamin Solomon, a medical oncologist at the Peter MacCallum Cancer Center in Melbourne, Australia, in a statement.
While Merck’s Keytruda largely dominates the NSCLC market, ALK-positive cases occur in about 3% to 5% of patients. In this area, Lorbrena is up against treatments from Roche and Novartis, which have given Xalkori a run for its money.
Xalkori received conditional approval for ALK-rearranged NSCLC in 2011, beating competitors to market. But Roche’s Alecensa, which was first approved in 2015, netted $334.6 million in Q4 of 2020, while Xalkori brought in only $135 million.