Chugai Pharmaceutical Co., Ltd., one of Japan’s leading research-based pharmaceutical companies, announced that Genentech Inc., a member of the Roche Group, obtained approval from the US Food and Drug Administration (FDA), for the anti-cancer agent, alectinib hydrochloride (Alecensa) for the indication of “anaplastic lymphoma kinase (ALK) positive, metastatic non-small cell lung cancer (NSCLC) who have progressed on or those intolerant to crizotinib.”

“Alecensa was created by Chugai and in July 2014, Japan became the first country in the World to receive approval. We believe that the FDA’s priority review of Alecensa will bring fresh hope for patients in the US living with this disease,” said Chugai’s director and executive vice president, Dr. Yutaka Tanaka.

“We are extremely pleased that Alecensa can contribute to the treatment of patients with ALK positive NSCLC.”

Alecensa was granted Breakthrough Therapy designation by FDA in June 2013 for patients with ALK positive NSCLC who have progressed on crizotinib. And FDA also granted priority review for Alecensa in September 2015.

The FDA’s Accelerated Approval Programme allows conditional approval of a medicine that fills an unmet medical need for a serious condition based on early evidence suggesting clinical benefit. The indication for Alecensa is approved under accelerated approval based on tumour response rate and duration of response (DOR). Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.

ALEX is a global, randomized phase III study comparing Alecensa to crizotinib as an initial treatment for people with advanced ALK-positive NSCLC. This study is part of the company’s commitment to convert the current accelerated approval in people with ALK-positive, metastatic NSCLC who have progressed on or are intolerant to crizotinib to a full approval as an initial treatment.

Alecensa is a highly selective ALK inhibitor created by Chugai. It has been reported that 2 to 5 per cent of patients with NSCLC express a chromosomal rearrangement which leads to fusion of the ALK gene with another gene. ALK kinase signaling is constantly active in cells with such fusion genes, resulting in uncontrolled growth of tumor cells and transforming the cells into tumour cells. Alecensa exerts its anti-tumour effect by selectively inhibiting ALK kinase activity to inhibit tumour cell proliferation and induce cell death4. In addition, Alecensa is not recognized by the transporter proteins in the blood brain barrier that actively pump molecules out of the brain. Alectinib is active in the central nervous system and has proven activity against brain metastases.

In Europe, Roche filed the NDA to the European Medicines Agency for the approval of “ALK fusion gene positive unresectable, recurrent/advanced NSCLC” in September 2015. Chugai has out-licensed the rights of Alecensa to Roche in overseas countries including Europe and the US.

In Japan, Alecensa capsule 20mg, 40mg and 150mg is available to patients with “ALK fusion gene positive unresectable, recurrent/advanced NSCLC” and is marketed by Chugai.

Overview of two pivotal clinical phase I/II trials is based on the US approval.

The NP28761 study is a phase I/II North American, single arm, open-label, multicentre trial evaluating the safety and efficacy of Alecensa in 87 people with ALK positive NSCLC whose disease progressed on crizotinib. (Data cut-off: October 24, 2014).

The NP28673 study is a phase I/II global, single arm, open-label, multicentre trial evaluating the safety and efficacy of Alecensa in 138 people with ALK positive NSCLC whose disease progressed on crizotinib. (Data cut-off: primary data cut-off including safety: August 18, 2014, updated IRC data cut-off: January 8, 2015).

People in the phase II studies received 600 mg of Alecensa orally twice daily. In both trials, the primary endpoint was ORR according to Response Evaluation Criteria in Solid Tumours (RECIST v1.1), and evaluated by an Independent Review Committee (IRC). Secondary endpoints included DOR and efficacy against disease that had spread to the CNS (CNS ORR and CNS DOR).

18 patients in study 1 and 16 patients in study 2 did not have measurable disease at baseline as per IRC assessment.

Of 51 people in the subgroup, 35 (69 per cent) had received prior brain radiation, including 25 (49 per cent) who completed radiation treatment at least six months before starting treatment with Alecensa.

The most common Grade 3 or higher adverse events in the pooled analysis of both studies were an increase in muscle enzymes (creatine phosphokinase; 4.6 per cent), shortness of breath (dyspnea; 3.6 per cent), increased liver enzymes (aspartate transaminase; 3.6 per cent, and alanine transaminase; 4.8 per cent), evidence of liver dysfunction (hyperbilirubinemia; 2.4 percent), increased blood glucose (hyperglycemia; 2 per cent), decreased levels of minerals (hypokalemia; 4 per cent, hypophosphatemia; 2.8 per cent, and hyponatremia; 2 per cent), decreased red blood cells (anemia; 2 per cent) and decreased white blood cells (lymphopenia; 4.6 per cent).