South San Francisco, CA May 18, 2016 Genentech Press Release 
First investigational head-to-head study of Alecensa versus crizotinib in people with advanced ALK-positive non-small cell lung cancer (NSCLC)
SOUTH SAN FRANCISCO, CA — 2016-05-18 00:00:00
Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY), today announced that Alecensa® (alectinib), an oral anaplastic lymphoma kinase (ALK) inhibitor, reduced the risk of disease worsening or death (progression-free survival, PFS) by 66 percent compared to crizotinib in Japanese people with advanced or recurrent, ALK-positive non-small cell lung cancer (NSCLC) (hazard ratio [HR]=0.34, 99 percent CI: 0.17-0.70, p<0.0001). Median PFS was not reached in people who received Alecensa (95 percent CI: 20.3 months-not reached) versus 10.2 months median PFS (95 percent CI: 8.2-12.0) in people who received crizotinib. The results were from a pre-specified interim analysis from the Phase III J-ALEX study in people who had not received prior treatment with an ALK inhibitor. There were fewer adverse events (AEs) in the Alecensa arm versus the crizotinib arm. Alecensa demonstrated a safety profile consistent with that observed in previous studies with no new or unexpected AEs.
“This is the first investigational study to show Alecensa helped people live longer without their disease getting worse compared to crizotinib,” said Sandra Horning, M.D., chief medical officer and head of Global Product Development. “We believe these efficacy and safety results represent a clinically meaningful advancement for people with ALK-positive lung cancer, and we plan to discuss these data with health authorities, including the FDA.”
The official data presentation at the American Society of Clinical Oncology (ASCO) annual meeting will be on Monday, June 6, from 12:09 – 12:21 P.M. CDT (Abstract #9008).
Alecensa was granted accelerated approval by the U.S. Food and Drug Administration (FDA) in December 2015 for the treatment of people with ALK-positive NSCLC who have progressed on or are intolerant to crizotinib. ALEX, a global, randomized Phase III study, is ongoing, comparing Alecensa to crizotinib as an initial (first-line) treatment for people with advanced NSCLC whose tumors were characterized as ALK-positive by a companion VENTANA ALK (D5F3) CDx Assay immunohistochemistry (IHC) test developed by Roche Tissue Diagnostics. 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.
About J-ALEX
The J-ALEX study conducted by Chugai is an open-label, randomized 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 randomized 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 AEs occurred with greater frequency in the crizotinib arm compared to the Alecensa arm (51 percent vs. 27 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), diarrhea (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 Lung Cancer
According to the American Cancer Society, it is estimated that more than 224,000 Americans will be diagnosed with lung cancer in 2016, 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 2 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 three 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 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.