Roche announced that the European Medicines Agency (EMA) for Medicinal Products for Human Use (CHMP) has adopted a positive opinion for the use of Alecensa (alectinib) for the treatment of adult patients with advanced anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC) whose disease has progressed following treatment with crizotinib. ALK-positive NSCLC occurs in approximately five per cent of people with advanced NSCLC, translating to about 75,000 people globally being diagnosed with the disease per year. ALK-positive disease is more common in light or non-smokers. Based on this positive CHMP recommendation, a final decision regarding the conditional marketing authorisation is expected from the European Commission in the coming months.
“Most people living with ALK-positive NSCLC develop resistance to the current standard of care, and nearly half see their tumours spread to the central nervous system within one year of treatment,” said Sandra Horning, MD, chief medical officer and head of global product development. “Today’s positive CHMP opinion is great news for people living with ALK-positive NSCLC and brings us one step closer to providing a much needed new treatment option for people and physicians in Europe.”
The EMA’s recommendation is based primarily on data from the pivotal studies NP28673 and NP28761. The studies showed that Alecensa shrank tumours in people with advanced ALK-positive NSCLC whose disease had progressed following treatment with crizotinib, overall response rate; ORR: 50.8 percent, (95% CI: 41.6%, 59.9%) and 52.2 percent (95% CI 39.7%, 64.6%) in NP28673 and NP28761, respectively. Alecensa extended the time that people lived without their disease worsening or death (progression-free survival, PFS) by 8.9 months, [5.6, 12.8] in the NP28673 study and 8.2 months, [6.3, 12.6] in the NP28761 study. In a pooled analysis of Central Nervous System (CNS) endpoints from studies NP28673 and NP28761 Alecensa shrank CNS tumours that were measurable in 64.0 percent of people [95% CI: 49.2%, 77.1%]. In addition, the people whose CNS tumours shrank in response to Alecensa continued to respond for a median of 11.1 months, CNS duration of response (DOR) [95% CI: 7.6, NE]. Twenty two percent (n=11) of people achieved a complete response of their measurable CNS tumours.
Alecensa as monotherapy is indicated for the treatment of adult patients with anaplastic lymphoma kinase (ALK) positive advanced non-small cell lung cancer (NSCLC) previously treated with crizotinib
Alecensa is approved in the United States, Kuwait, Israel, Canada, Hong Kong and South Korea for the treatment of ALK-positive metastatic NSCLC patients who have progressed on or are intolerant to crizotinib. Alecensa is also approved for use in Japan. In addition, Alecensa is being explored as a first-line treatment option with the phase III ALEX and J-ALEX studies comparing Alecensa to crizotinib, the current standard of care. Results from the J-ALEX study were presented at the 2016 American Society of Clinical Oncology (ASCO) annual meeting and showed that Alecensa reduced the risk of disease worsening or death (progression-free survival, PFS) by 66 percent (hazard ratio [HR]=0.34, 99% CI: 0.17-0.70, p<0.0001) compared to crizotinib in this specific form of lung cancer.
Lung cancer is the leading cause of cancer death globally. Each year 1.59 million people die as a result of the disease; this translates into more than 4,350 deaths worldwide every day. Lung cancer can be broadly divided into two major types: NSCLC and small cell lung cancer. NSCLC is the most prevalent type, accounting for around 85% of all cases.
NP28673 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.
The study showed by assessment of an independent review committee (IRC) an ORR of 50.8 percent (95% CI: 41.6%, 60.0%), as measured by RECIST criteria.
An investigator assessment also showed tumours shrank in 51.4 percent of people who received Alecensa.
In addition, the people whose tumours shrank in response to Alecensa continued to respond for a median of 15.2 months (95% CI: 11.2, 24.9) (duration of response; DOR).
The median PFS for people who received Alecensa was 8.9 months (95% CI: 5.6, 12.8). Alecensa demonstrated a safety profile consistent with that observed in previous studies.
The most common (occurring in at least two percent of people) Grade 3 or higher adverse event was shortness of breath (dyspnoea; four percent).
NP28761 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.
The study showed by assessment of an independent review committee (IRC) an ORR of 52.2 percent (95% CI: 39.7%, 64.6%) as measured by RECIST criteria.
An investigator assessment showed tumours shrank in 52.9 percent of people who received Alecensa (95% CI: 41.9%, 63.7%). In addition, the people whose tumours shrank in response to Alecensa continued to respond for a median of 14.9 months (95% CI: 6.9, NE) (DOR). The median PFS for people who received Alecensa was 8.2 months (95% CI: 6.3, 12.6). Alecensa demonstrated a safety profile consistent with that observed in previous studies.
The most common (occurring in at least two percent of people) Grade 3 or higher adverse events were an increase in muscle enzymes (increased blood levels of creatine phosphokinase; eight percent), increased liver enzymes (alanine aminotransferase; six percent, and aspartate aminotransferase; five percent) and shortness of breath (dyspnoea; three percent), elevated levels of triglyceride (hypertriglyceridaemia), increased potassium level (hypokalaemia) and low levels of phosphate in the blood (hypophosphatemia; three percent). Partial blood thickening (thromboplastin; two percent) time prolonged.
Alecensa (RG7853/AF-802/RO5424802/CH5424802) is an oral medicine created at Chugai Kamakura.
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, Japan, Kuwait, Israel, Hong Kong, Canada and South Korea for the treatment of advanced (metastatic) ALK-positive NSCLC whose disease has worsened after, or who could not tolerate treatment with, crizotinib.
In a pooled analysis of Central Nervous System (CNS) endpoints from studies NP28673 and NP28761 Alecensa 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 ALEX study of Alecensa includes a companion test developed by Roche Diagnostics. Alecensa is marketed in Japan by Chugai Pharmaceutical, a member of the Roche Group.