Roche isn’t content with Alecensa being the best-selling ALK inhibitor in metastatic lung cancer. The Swiss pharma has now secured FDA approval in the post-surgical setting as it continues to test the drug in additional patient populations.
The FDA has approved Alecensa as an adjuvant treatment following tumor resection in patients with early-stage, ALK-positive non-small cell lung cancer, Roche’s Genentech unit said on Thursday.
The approval came more than a month ahead of the agency’s original target decision date in May, a Genentech spokesperson told Fierce Pharma. The FDA conducted the review under Project Orbis, which allows the U.S. agency to collaborate with drug regulators in other countries. Authorities in Australia, Canada, Israel, Switzerland and the U.K. participated in the review of this Alecensa application.
Alecensa has shown “robust and compelling” clinical data in this indication, Genentech’s head of oncology and hematology global product development, Charlie Fuchs, M.D., said in an interview.
In the phase 3 ALINA trial conducted in patients with surgically resected stage 1b to 3a ALK-positive NSCLC, Alecensa cut the risk of disease recurrence or death by a whopping 76% compared with platinum-based chemotherapy.
In the main efficacy analysis, which focused on patients with stage 2 to 3a tumors, Alecensa’s effect size was the same at 76%. At two years, 93.8% of Alecensa takers with those stages of tumors were alive and disease-free, versus 63% in the chemotherapy group.
About half of patients with early ALK-positive NSCLC typically recur following post-operative chemo, and about 50% to 60% of patients will develop brain metastases, Fuchs said.
In ALINA, Alecensa also reduced the risk of recurrence in the central nervous system or death by 78% versus chemotherapy.
Data on whether Alecensa can extend patients’ lives in this curative-intent setting remained immature during the review. The 257-patient trial has so far only recorded six deaths, including just two in the Alecensa arm, according to results published a few days ago in the New England Journal of Medicine.
The lack of a definitive overall survival showing could translate into some reluctance among doctors toward using Alecensa in this early-stage setting, especially as ALK inhibitors are established standard treatments for metastatic disease.
This could be evidenced by the fact that AstraZeneca’s EGFR inhibitor Tagrisso has experienced some resistance as a postoperative adjuvant therapy also in a biomarker-defined NSCLC population. Despite a massive 83% recurrence-free survival benefit against placebo, Tagrisso previously couldn’t win over some doctors who would rather see an overall survival improvement.
Still, Fuchs argued it’s probably in the best interest of patients to intervene early, given Alecensa’s ability to prevent recurrence or brain metastases.
“I would hope that practitioners would be willing to consider that, because obviously, waiting for recurrence in this setting of ALK-positive disease is such a troubling issue,” Fuchs said. “But obviously, I think it’s important for practitioners to really get a chance to become comfortable with the data [and] gain experience.”
With 1.5 billion Swiss francs ($1.65 billion) in 2023 sales, Alecensa is the top-selling med in the ALK inhibitor class, which also includes Takeda’s Alunbrig and Pfizer’s next-generation ALK/ROS1 inhibitor Lorbrena.
Besides the adjuvant setting for resected tumors, Roche is also testing Alecensa in patients with locally advanced, unresectable, stage 3 NSCLC in the phase 3 HORIZON-01 trial. Another study is evaluating the drug as a neoadjuvant treatment used before surgery.
Alecensa’s ALINA win came after several setbacks for Roche’s PD-L1 inhibitor Tecentriq in various adjuvant settings. Apart from definite failures in head and neck cancer and triple-negative breast cancer, Tecentriq in the IMBrave050 trial showed a disease recurrence-free survival benefit but a preliminary negative trend in patient survival for the adjuvant treatment of liver cancer.
After detailing the results a year ago, Roche has not shared a regulatory plan for that study.
On Tecentriq, Fuchs declined to comment on Roche’s communications with the FDA but said the company expects to report more mature overall survival data this year from the IMBrave050 trial. The previous readout was based on only 7% of death events required for a final overall survival analysis.