On 11 December, 2015 the US Food and Drug Administration (FDA) approved alectinib (Alecensa) for treatment of patients with advanced (metastatic) ALK-positive non-small cell lung cancer (NSCLC) whose disease has progressed after, or who could not tolerate treatment with, another ALK inhibitor, crizotinib (Xalkori).
An ALK (anaplastic lymphoma kinase) gene mutation can occur in several different types of cancer cells, including lung cancer. ALK gene mutations are present in about 5% of patients with NSCLC. In ALK-positive NSCLC metastatic patients, the brain is a common place for metastatic spread. Dr Richard Pazdur, director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research said: “In addition to the primary effect on tumors in the lung, Alecensa clinical trials provide evidence of an effect on tumors that had spread to the brain, which is an important effect for clinicians to understand.”
Alecensa is an oral medication; the second generation of ALK inhibitor.
The safety and efficacy of Alecensa were studied in two single-arm clinical trials of patients with metastatic ALK-positive NSCLC whose disease was no longer controlled by treatment with Xalkori. Study participants received Alecensa twice daily to measure the drug’s effect. In the first study, 38% of participants experienced a partial shrinkage of their NSCLC tumours, an effect that lasted for an average of 7.5 months. In the second study, 44% of participants experienced a partial shrinkage of their NSCLC tumours, lasting for an average of 11.2 months.
The trials also examined Alecensa’s effect on brain metastases, a common occurrence in this population. Among the participants in the two trials, who had measurable brain metastases, 61% experienced a complete or partial reduction in their brain metastases, lasting an average of 9.1 months.
The most common side effects of Alecensa are fatigue, constipation, oedema and myalgia. Alecensa may cause serious side effects, including hepatotoxicity, severe or life-threatening pneumonitis, bradycardia and severe muscle problems. Treatment with Alecensa may cause sunburn when patients are exposed to sunlight.
Alecensa was approved using the accelerated approval regulatory pathway, which allows the FDA to approve products for serious or life-threatening diseases based on evidence that the product has an effect on an outcome that is reasonably likely to predict clinical benefit. In the case of Alecensa, the tumour response to treatment, along with the duration of response, provided this evidence. Under the accelerated approval requirements, a confirmatory study is required to verify and describe the clinical benefit of Alecensa.
The FDA granted the Alecensa application breakthrough therapy designation and priority review status. These are distinct programmes intended to facilitate and expedite the development and review of certain new drugs in light of their potential to benefit patients with serious or life-threatening conditions. Alecensa also received orphan drug designation, which provides incentives such as tax credits, user fee waivers and eligibility for exclusivity to assist and encourage the development of drugs for rare diseases.
Alecensa is marketed by Genentech, based in San Francisco, California.
Xalkori is marketed by Pfizer, based in New York, New York.