On October 4, 2016 Roche (SIX: RO, ROG; OTCQX: RHHBY) reported that it has received a second Breakthrough Therapy Designation (BTD) from the United States Food and Drug Administration (FDA) for its ALK inhibitor, Alecensa (alectinib) (Press release, Hoffmann-La Roche , OCT 4, 2016, View Source [SID:SID1234515583]). The latest BTD was granted for the treatment of adult patients with advanced anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC) who have not received prior treatment with an ALK inhibitor.

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"The J-ALEX study that supports the second Breakthrough Designation for Alecensa showed superior efficacy versus the standard of care, crizotinib, in Japanese people with advanced ALK-positive disease," said Sandra Horning, MD, Chief Medical Officer and Head of Global Product Development. "The decision by the FDA to grant a second breakthrough therapy designation is recognition of the clinically meaningful improvement in efficacy and safety that Alecensa brings to the care of people with advanced ALK-positive lung cancer who have not received prior treatment with an ALK inhibitor."

This second breakthrough therapy designation is based on the results of the open-label, randomised phase III J-ALEX study, which were presented at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) 2016 Annual Meeting in June. J-ALEX compared the efficacy and safety of Alecensa with crizotinib in 207 Japanese people with ALK-positive, advanced or recurrent NSCLC who either had not been treated with chemotherapy or had received one prior line of chemotherapy. Results from the study demonstrated that Alecensa reduced the risk of disease worsening or death (progression-free survival, PFS) by 66% compared to crizotinib, whilst maintaining a favourable tolerability and safety profile consistent with that observed in previous studies.

The FDA’s Breakthrough Therapy Designation is designed to expedite the development and review of medicines intended to treat serious diseases and to help ensure patients have access to them through FDA approval as soon as possible. Alecensa received its first FDA BTD in June 2013 for people with ALK-positive NSCLC whose disease progressed on treatment with crizotinib.

Alecensa is currently available in the US and Israel to ALK-positive metastatic NSCLC patients who have progressed on or are intolerant to crizotinib, and in Japan to ALK-positive unresectable, recurrent or advanced NSCLC patients. In addition, an ongoing global, randomised phase III trial called ALEX is comparing Alecensa to Xalkori as an initial (first-line) treatment for people with advanced ALK-positive NSCLC.

About J-ALEX
The J-ALEX study conducted by Chugai is an open-label, randomised Phase III study that compared the efficacy and safety of Alecensa to crizotinib in Japanese people. The J-ALEX study enrolled 207 people with ALK-positive, advanced or recurrent NSCLC who had not been previously treated with an ALK inhibitor. People were randomised to the Alecensa group or the crizotinib group in a one-to-one ratio. Results include:

Alecensa reduced the risk of disease worsening or death (PFS) by 66 percent compared to crizotinib (HR=0.34, 99 percent CI: 0.17-0.70, p<0.0001).

Median PFS was not reached in the Alecensa arm (95 percent CI: 20.3 months-not estimated) versus 10.2 months in the crizotinib arm (95 percent CI: 8.2-12.0).

Grade 3-4 adverse events (AE) occurred with lesser frequency in the Alecensa arm compared to the crizotinib arm (27 percent vs. 51 percent).

The most common AE occurring with > 30 percent frequency with Alecensa was constipation (36 percent). The most common AEs for crizotinib were nausea (74 percent), diarrhoea (73 percent), vomiting (59 percent), visual disturbance (55 percent), alteration in taste (dysgeusia, 52 percent), constipation (46 percent), and an elevation in liver enzymes called alanine transaminase (ALT, 32 percent) and aspartate transaminase (AST, 31 percent).

About Alecensa
Alecensa (RG7853/AF-802/CH5424802) is an oral medicine created at Chugai Research Laboratories and is being developed for people with NSCLC whose tumours are identified as ALK-positive. ALK-positive NSCLC is often found in younger people who have a light or non-smoking history. It is almost always found in people with a specific type of NSCLC called adenocarcinoma. Alecensa is currently approved in the United States for the treatment of people with advanced (metastatic) ALK-positive NSCLC whose disease has worsened after, or who could not tolerate treatment with, crizotinib.

In two key phase II studies, NP28761 and NP28673, Alecensa shrank tumours in up to 44% of people with ALK-positive NSCLC who progressed on crizotinib. Alecensa also demonstrated activity in brain metastases, indicating that the drug may be taken up in the brain. The brain is protected by the Blood-Brain
Barrier, a network of tightly joined cells that line the inside of the blood vessels in the brain and spinal cord.

One of the ways the Blood-Brain Barrier prevents molecules from affecting the brain is to actively eject them from the barrier through a process known as ‘active efflux’. The active efflux system does not recognise
Alecensa, which means that it may travel into and throughout brain tissue.

The global phase III studies of Alecensa include a companion test developed by Roche Diagnostics. Alecensa is marketed in Japan by Chugai Pharmaceutical, a member of the Roche Group.

About ALK-positive non-small cell lung cancer
Lung cancer is the biggest cancer killer, causing 1.59 million deaths globally each year. NSCLC is the most common type of lung cancer, and is the leading cause of cancer-related deaths in Europe and across the world, accounting for approximately 85% of lung cancer cases. ALK-positive NSCLC occurs in approximately 5% of patients with advanced NSCLC, translating to about 75,000 patients being diagnosed with the disease annually. It is almost always found in people with a specific type of NSCLC called adenocarcinoma, and is more common in light or non-smokers.