CHMP recommends EU conditional approval of Roche’s Alecensa (alectinib) for people with previously treated ALK-positive NSCLC

Roche (SIX: RO, ROG; OTCQX: RHHBY) announced today 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 percent 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.^3,1  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. ^2-5  

About the NP28673 study

• 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).

About the NP28761 study

• 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. 

About Alecensa

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.

About Roche in lung cancer

Lung cancer is a major area of focus and investment for Roche, and we are committed to developing new approaches, medicines and tests that can help people with this deadly disease. Our goal is to provide an effective treatment option for every person diagnosed with lung cancer. We currently have four approved medicines to treat certain kinds of lung cancer and more than ten medicines being developed to target the most common genetic drivers of lung cancer or to boost the immune system to combat the disease.

About Roche

Roche is a global pioneer in pharmaceuticals and diagnostics focused on advancing science to improve people’s lives.

Roche is the world’s largest biotech company, with truly differentiated medicines in oncology, immunology, infectious diseases, ophthalmology and diseases of the central nervous system. Roche is also the world leader in in vitro diagnostics and tissue-based cancer diagnostics, and a frontrunner in diabetes management. The combined strengths of pharmaceuticals and diagnostics under one roof have made Roche the leader in personalised healthcare – a strategy that aims to fit the right treatment to each patient in the best way possible.

Founded in 1896, Roche continues to search for better ways to prevent, diagnose and treat diseases and make a sustainable contribution to society. Twenty-nine medicines developed by Roche are included in the World Health Organization Model Lists of Essential Medicines, among them life-saving antibiotics, antimalarials and cancer medicines. Roche has been recognised as the Group Leader in sustainability within the Pharmaceuticals, Biotechnology & Life Sciences Industry eight years in a row by the Dow Jones Sustainability Indices.

The Roche Group, headquartered in Basel, Switzerland, is active in over 100 countries and in 2015 employed more than 91,700 people worldwide. In 2015, Roche invested CHF 9.3 billion in R&D and posted sales of CHF 48.1 billion. Genentech, in the United States, is a wholly owned member of the Roche Group. Roche is the majority shareholder in Chugai Pharmaceutical, Japan. For more information, please visit www.roche.com.

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References
¹ Very Well. ALK Positive Lung Cancer Definition and Treatment. Last accessed July 2016 at https://www.verywell.com/what-is-alk-positive-lung-cancer-2248944.

² European Cancer Observatory 2012. Estimated cancer incidence and mortality in European Union. Last accessed July 2016 at http://eco.iarc.fr/eucan/Country.aspx?ISOCountryCd=930.

³ GLOBOCAN 2012. Estimated cancer incidence, mortality and prevalence worldwide in 2012. Last accessed July 2016 at http://globocan.iarc.fr/Pages/fact_sheets_population.aspx.

⁴ Barzi A and Pennell NA, European J Clin Med Oncol. 2010; 2: 31-42.

⁵ Torre L, et al. CA: Cancer J Clin 2015; 65: 87-108.