Monday, Jun 5, 2017

Phase III Study Showed Genentech’s Alecensa (Alectinib) Reduced the Risk of Disease Progression or Death by More Than Half Versus Crizotinib as First-Line Treatment in a Specific Type of Lung Cancer

Second positive Phase III head-to-head study to show Alecensa was superior to crizotinib in people with ALK-positive lung cancer

Alecensa lowered the risk of tumor spread or growth in the brain or central nervous system

Data will be simultaneously published in the New England Journal of Medicine and featured in the official ASCO press program

Chicago -- June 5, 2017 --

Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY), today announced that the Phase III ALEX study showed Alecensa® (alectinib) significantly reduced the risk of disease worsening or death (progression-free survival, PFS) by more than half (53 percent) compared to crizotinib when given as initial (first-line) treatment for people with anaplastic lymphoma kinase (ALK)-positive advanced non-small cell lung cancer (NSCLC) (hazard ratio [HR]=0.47, 95 percent CI: 0.34-0.65, p<0.0001). Median PFS reported by the investigators, the primary endpoint of the study, was not yet reached in people who received Alecensa (95 percent CI: 17.7-not reached) versus 11.1 months (95 percent CI: 9.1-13.1 months) in those who received crizotinib. Median PFS assessed by an independent review committee (IRC), a secondary endpoint, was 25.7 months (95 percent CI: 19.9-not reached) for people who received Alecensa versus 10.4 months (95 percent CI: 7.7-14.6 months) for people who received crizotinib (HR=0.50, 95 percent CI: 0.36-0.70, p<0.0001). The safety profile of Alecensa was consistent with that observed in previous studies.

“Alecensa reduced the risk of disease progression by more than half and reduced the risk of cancer spreading to or growing in the brain, which can have devastating effects for patients,” said Sandra Horning, M.D., chief medical officer and head of Global Product Development. “These results significantly improve upon the standard of care for this disease, extending the average time that people lived without their disease worsening from less than a year to more than two years. We are submitting these data to regulatory authorities around the world.”

The global, randomized Phase III ALEX study also demonstrated that Alecensa reduced the risk of disease progression in the central nervous system (CNS) by 84 percent (HR=0.16, 95 percent CI: 0.10-0.28, p<0.0001). The 12-month cumulative rate of CNS progression for people with or without existing CNS metastases at baseline was 9.4 percent (95 percent CI: 5.4-14.7 percent) for people treated with Alecensa and 41.4 percent (95 percent CI: 33.2-49.4 percent) for people treated with crizotinib.

The official ALEX data presentation at the American Society of Clinical Oncology (ASCO) annual meeting will be on Tuesday, June 6, 2017, at 12:09 – 12:21 p.m. CST (Abstract #9008). The data will be simultaneously published in the New England Journal of Medicine and will be featured in the official ASCO press program on Monday, June 5, 2017, at 8:00 a.m. CST.

Data from the ALEX study will be submitted to global health authorities, including the U.S. Food and Drug Administration (FDA), which in September 2016 granted Alecensa Breakthrough Therapy Designation (BTD) for the treatment of people with advanced ALK-positive NSCLC who have not received prior treatment with an ALK inhibitor.

Alecensa was granted accelerated approval by the FDA in December 2015 for the treatment of people with ALK-positive NSCLC who have progressed on or are intolerant to crizotinib. The ALEX study is part of the company’s commitment in the U.S. to convert the current accelerated approval of Alecensa in people with ALK-positive, metastatic NSCLC who have progressed on or are intolerant to crizotinib to a full approval as an initial treatment.

About the ALEX Study

ALEX (NCT02075840/B028984) is a randomized, multicenter, open-label Phase III study evaluating the efficacy and safety of Alecensa versus crizotinib in treatment-naïve people with ALK-positive NSCLC whose tumors were characterized as ALK-positive by the VENTANA ALK (D5F3) CDx Assay, a companion immunohistochemistry (IHC) test developed by Roche Tissue Diagnostics. People were randomized (1:1) to receive either Alecensa or crizotinib. The primary endpoint of the ALEX study is PFS as assessed by the investigator and secondary endpoints include: IRC-assessed PFS, time to CNS progression, objective response rate (as defined by RECIST criteria), duration of response, overall survival, health-related quality of life and safety. The multicenter study was conducted in 303 people across 161 sites in 31 countries. Results include:

  • Alecensa reduced the risk of disease worsening or death (PFS) by 53 percent compared to crizotinib (HR=0.47, 95 percent CI: 0.34-0.65, p<0.0001).
  • Investigator-reported median PFS (the primary endpoint) was not yet reached in the Alecensa arm (95 percent CI: 17.7-not reached) versus 11.1 months (95 percent CI: 9.1-13.1 months) in the crizotinib arm.
  • IRC-reported median PFS (a secondary endpoint) was 25.7 months (95 percent CI: 19.9-not reached) in the Alecensa arm versus 10.4 months (95 percent CI: 7.7-14.6 months) in the crizotinib arm (HR=0.50, 95 percent CI: 0.36-0.70, p<0.0001).
  • Alecensa reduced the risk of progression in the CNS by 84 percent (HR=0.16, 95 percent CI: 0.10-0.28, p<0.0001).
  • The 12-month cumulative rate of CNS progression for people with or without existing CNS metastases at baseline was 9.4 percent (95 percent CI: 5.4-14.7 percent) for people treated with Alecensa and 41.4 percent (95 percent CI: 33.2-49.4 percent) for people treated with crizotinib.
  • Overall survival (OS) data are currently considered immature with only about a quarter of events being reported.
  • Grade 3-5 adverse events (AEs) were less frequent in the Alecensa arm (41 percent) compared to the crizotinib arm (50 percent). In the Alecensa arm, the most common Grade 3-5 AEs (≥5 percent) were increased liver enzymes (alanine transferase and aspartate transferase; 5 percent) and decreased red blood cells (anemia; 5 percent). AEs leading to discontinuation (11 percent vs. 13 percent), dose reduction (16 percent vs. 21 percent) and dose interruption (19 percent vs. 25 percent) were all lower in the Alecensa arm compared to the crizotinib arm.

About Lung Cancer

According to the American Cancer Society, it is estimated that more than 222,000 Americans will be diagnosed with lung cancer in 2017, and NSCLC accounts for 85 percent of all lung cancers. It is estimated that approximately 60 percent of lung cancer diagnoses in the United States are made when the disease is in the advanced stages.

About Alecensa

Alecensa is a kinase inhibitor approved for the treatment of people with anaplastic lymphoma kinase (ALK)-positive, metastatic non-small cell lung cancer (NSCLC) who have progressed on or are intolerant to crizotinib. This indication is approved under accelerated approval based on tumor response rate and duration of response (DOR). Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

Important Safety Information

Everyone reacts differently to treatment with Alecensa. It’s important to know the most serious and most common side effects with Alecensa.

A doctor may lower the dose or stop treatment with Alecensa if any serious side effects occur. Patients taking Alecensa should contact their doctor right away if they have any of the following side effects.

Alecensa may cause serious side effects, including:

Liver problems (hepatotoxicity). Alecensa may cause liver injury. A doctor will do blood tests at least every 2 weeks for the first 3 months and as needed during treatment with Alecensa. Patients taking Alecensa should tell their doctor right away if they experience any of the following signs and symptoms:

  • Feeling tired
  • Feeling less hungry than usual
  • Yellowing of the skin or whites of the eyes
  • Dark urine
  • Itchy skin
  • Nausea or vomiting
  • Pain on the right side of stomach area
  • Bleeding or bruising more easily than normal

Lung problems. Alecensa may cause severe or life-threatening swelling (inflammation) of the lungs during treatment.

Symptoms may be similar to those symptoms from lung cancer. Patients taking Alecensa should tell their doctor right away if they have any new or worsening symptoms, including:

  • Trouble breathing
  • Shortness of breath
  • Fever
  • Cough

Slow heartbeat (bradycardia). Alecensa may cause very slow heartbeats that can be severe. A doctor will check a patient’s heart rate and blood pressure during treatment with Alecensa. Patients taking Alecensa should tell their doctor right away if they feel dizzy, lightheaded, or faint during treatment with Alecensa. Patients taking Alecensa should tell their doctor if they take any heart or blood pressure medicines.

Muscle pain, tenderness, and weakness (myalgia). Muscle problems are common with Alecensa and can be severe. A doctor will do blood tests at least every 2 weeks for the first month and as needed during treatment with Alecensa. Patients taking Alecensa should tell their doctor right away if they have any new or worsening signs and symptoms of muscle problems, including unexplained muscle pain or muscle pain that does not go away, tenderness, or weakness.

Before taking Alecensa, patients should tell their doctor about all medical conditions, including if they:

  • Have liver problems
  • Have lung or breathing problems
  • Have a slow heartbeat
  • Are pregnant or plan to become pregnant. Alecensa can harm an unborn baby. Patients taking Alecensa should tell their doctor right away if they become pregnant during treatment with Alecensa or think they may be pregnant
    • Women who are able to become pregnant should use effective birth control during treatment with Alecensa and for one week after the final dose of Alecensa
    • Men who have female partners that are able to become pregnant should use effective birth control during treatment with Alecensa and for three months after the final dose of Alecensa
  • Are breastfeeding or plan to breastfeed. It is not known if Alecensa passes into breast milk. A patient should not breastfeed during treatment with Alecensa and for one week after the final dose of Alecensa. Patients should talk with their doctor about the best way to feed their baby during this time.

Patients taking Alecensa should tell their doctor about all the medicines they take, including prescription medicines, over-the-counter medicines, vitamins, and herbal supplements.

Patients taking Alecensa should avoid spending time in the sunlight during treatment with Alecensa and for seven days after the final dose of Alecensa. Patients taking Alecensa may burn more easily and get severe sunburns. Patients taking Alecensa should use sunscreen and lip balm with a SPF 50 or greater to help protect against sunburn.

The most common side effects of Alecensa include:

  • Tiredness
  • Constipation
  • Swelling in hands, feet, ankles, and eyelids

These are not all of the possible side effects of Alecensa. For more information, patients should ask their doctor or pharmacist. Patients should call their doctor for medical advice about side effects.

Report side effects to the FDA at (800) FDA-1088 or http://www.fda.gov/medwatch . Patients and caregivers may also report side effects to Genentech at (888) 835-2555.

Please see additional Important Safety Information in full Prescribing Information , including Patient Information .

About Genentech in Lung Cancer

Lung cancer is a major area of focus and investment for Genentech, 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 10 medicines being developed to target the most common genetic drivers of lung cancer or to boost the immune system to combat the disease.

About Genentech

Founded more than 40 years ago, Genentech is a leading biotechnology company that discovers, develops, manufactures and commercializes medicines to treat patients with serious or life-threatening medical conditions. The company, a member of the Roche Group, has headquarters in South San Francisco, California. For additional information about the company, please visit http://www.gene.com.

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