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Takeda's Alunbrig Gets First-Line FDA Approval With Abbott CDx in ALK-Positive Lung Cancer

This story has been updated with additional details on the FDA approved companion test for Alunbrig and about how patients were genetically tested in the ALTA 1L study. 

NEW YORK – The US Food and Drug Administration on Friday approved Takeda Pharmaceutical's brigatinib (Alunbrig) as a treatment for ALK-positive, metastatic non-small cell lung cancer.

The agency simultaneoulsy approved Abbott Molecular's Vysis ALK Break Apart FISH Probe Kit to identify patients with ALK rearrangements who are likely to benefit from brigatinib.

The latest approval makes brigatinib a first-line option in this setting. Brigatinib was first approved in the US in 2017 as a treatment for ALK-positive, metastatic NSCLC patients who had progressed on or were intolerant to crizotinib (Pfizer's Xalkori). Between 3 percent and 5 percent of metastatic NSCLC patients harbor ALK rearrangements.

The FDA approved the latest indication based on the Phase III ALTA 1L trial, which compared the safety and efficacy of brigatinib against crizotinib in patients with ALK-positive advanced or metastatic NSCLC who had never before received an ALK inhibitor. 

In the study, 137 patients received brigatinib and 138 received crizotinib. Around 30 percent of patients in each arm had brain metastasis and more than a quarter of patients in both arms had received prior chemotherapy. After more than two years of follow up, half as many patients in the brigatinib-treated arm experienced progression or death compared to those in the crizotinib arm, and the median progression-free survival was 24 months versus 11 months, respectively.

In the brigatinib arm, 74 percent of the patients saw their tumors shrink compared to 62 percent in crizotinib arm. The confirmed intracranial overall response rate was 78 percent for those with brain metastasis at baseline and on brigatinib, compared to 26 percent on crizotinib.

The trial allowed patients to receive local ALK testing, and did not require confirmation at a centralized lab. In announcing the approval of this latest indicaiton, the FDA noted that a subset of the clinical samples in ALTA 1L was retrospectively tested with the Vysis ALK Break Apart FISH Probe Kit. Among the enrolled patients, 239 had positive results using Abbott's test, central lab test results were negative for 20 and unavailable for 16 patients. 

"Results from the ALTA 1L trial add brigatinib to the very short list of first-line treatment options for ALK-positive lung cancer patients that have proven to be superior to crizotinib," Ross Camidge from the University of Colorado Cancer Center, who led the study, said in a statement. "Compared to crizotinib, brigatinib demonstrated superior efficacy, especially among those with brain metastases at baseline, and a low pill burden, at one pill a day, which is an important factor when we could be controlling disease for years."

Brigatinib's label includes warnings about the risk of interstitial lung disease, hypertension, bradycardia, and visual disturbances. In ALTA 1L, 33 percent of patients on brigatinib experienced serious adverse events, with the most common being pneumonia, interstitial lung disease, and pyrexia.

The European Commission approved this same indication for brigatinib earlier this year.

In 2018, Thermo Fisher Scientific inked a companion diagnostic deal with Takeda to expand the indications on its Oncomine Dx Target Test next-generaiton sequencing test to include evaluation of the ALK gene. 

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