SOUTH SAN FRANCISCO, Calif.--(BUSINESS WIRE)--Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY), today announced that the U.S. Food and Drug Administration (FDA) approved the supplemental New Drug Application (sNDA) for Alecensa® (alectinib) for the treatment of people with anaplastic lymphoma kinase (ALK)-positive metastatic non-small cell lung cancer (NSCLC) as detected by an FDA-approved test. The approval is based on results from the Phase III ALEX study, which showed Alecensa significantly reduced the risk of disease worsening or death (progression-free survival, PFS) by 47 percent (HR=0.53, 95 percent CI: 0.38, 0.73, p<0.0001) compared to crizotinib as assessed by independent review committee (IRC). Median PFS was 25.7 months (95 percent CI: 19.9, not estimable) for people who received Alecensa compared with 10.4 months (95 percent CI: 7.7, 14.6) for people who received crizotinib. The safety profile of Alecensa was consistent with that observed in previous studies.
The study also showed that Alecensa significantly reduced the risk of the cancer spreading to or growing in the brain or central nervous system (CNS) compared to crizotinib by 84 percent (HR=0.16, 95 percent CI: 0.10, 0.28, p<0.0001). This was based on a time to CNS progression analysis in which there was a lower risk of progression in the CNS as the first site of disease progression for people who received Alecensa (12 percent) compared to people who received crizotinib (45 percent).
“Our goal is to develop medicines that have the potential to significantly improve upon the standard of care,” said Sandra Horning, M.D., chief medical officer and head of Global Product Development. “In our pivotal study, Alecensa significantly extended the time that people lived without their disease worsening compared to crizotinib and also showed a marked reduction in the risk of their cancer spreading to the brain.”
“ALK-positive lung cancer is often found in younger people, who tend to have more advanced disease at the time of diagnosis, and comes with a unique set of challenges," said Bonnie J. Addario, a lung cancer survivor and founder of the Bonnie J. Addario Lung Cancer Foundation (ALCF). “We applaud advancements in care, like the approval of Alecensa, which provides a new initial treatment option for people with this type of lung cancer.”
Alecensa received Breakthrough Therapy Designation from the FDA in September 2016 for the treatment of adults with advanced ALK-positive NSCLC who have not received prior treatment with an ALK inhibitor. Breakthrough Therapy Designation is designed to expedite the development and review of medicines intended to treat serious or life-threatening diseases and to help ensure people have access to them through FDA approval as soon as possible. Results from the Phase III ALEX study were simultaneously presented at the 2017 American Society of Clinical Oncology (ASCO) Annual Meeting and published in The New England Journal of Medicine. Subsequently, Alecensa was recommended in the National Comprehensive Cancer Network (NCCN) guidelines as a treatment option for first-line ALK-positive metastatic NSCLC (Category 1, Preferred).
In addition to today’s approval, the FDA also converted Alecensa’s initial accelerated approval in December 2015 for the treatment of people with ALK-positive, metastatic NSCLC who have progressed on or are intolerant to crizotinib (second-line) to a full approval.
About the ALEX study
ALEX (NCT02075840/B028984) is an open-label, randomized, active-controlled, multicenter, Phase III study evaluating the efficacy and safety of Alecensa versus crizotinib in people with ALK-positive NSCLC who had not received prior systemic therapy for metastatic disease and whose tumors were characterized as ALK-positive by the VENTANA ALK (D5F3) CDx Assay, an immunohistochemistry (IHC) test developed by Roche Tissue Diagnostics. People were randomized (1:1) to receive either Alecensa or crizotinib. The major efficacy outcome measure of the ALEX study is PFS according to RECIST v1.1 as determined by investigator assessment. Additional efficacy outcome measures include: PFS as determined by IRC, time to CNS progression by IRC based on RECIST v1.1, objective response rate (ORR) and duration of response (DOR), and overall survival (OS). Additional exploratory outcome measures were CNS-ORR and CNS-DOR by IRC in people with measurable CNS metastases at baseline. The multicenter study was conducted in 303 people across 161 sites in 31 countries. OS data are currently considered immature with only about a quarter of events being reported. Results include:
Summary of ALEX Study Key Efficacy Endpoints Per IRC Assessment
|Progression-Free Survival (PFS)|
|Number of Events (%)||63 (41)||92 (61)|
Progressive Disease (%)
|51 (34)||82 (54)|
|Death (%)||12 (8)||10 (7)|
Median in months (95% CI) PFS
|25.7 (19.9, NE)||10.4 (7.7, 14.6)|
Hazard Ratio (HR) (95% CI)a
|0.53 (0.38, 0.73)|
|Overall Response Rate (ORR)|
ORR (%) (95% CI)c
|79 (72, 85)||72 (64, 79)|
|Complete Response (%)||13||6|
|Partial Response (%)||66||66|
|Duration of Response (DOR)|
|Number of Responders||n=120||n=109|
|Response Duration ≥ 6 months (%)||82||57|
|Response Duration ≥ 12 months (%)||64||36|
|Response Duration ≥ 18 months (%)||37||14|
a, b, d Stratified by race (Asian vs. non-Asian) and CNS metastases at baseline (yes v. no) for Cox model, log-rank test and Cochran Mantel-Haenszel test, respectively.
|c Clopper and Pearson exact binomial 95 percent confidence interval.|
|CNS: central nervous system, ORR: overall response rate, IRC: independent review committee, CI: confidence interval, NE: not estimable|
|IRC-Assessed CNS Responses in People with Measurable CNS Lesions at Baseline|
|CNS Tumor Response Assessment||n=21||n=22|
CNS ORR (%) (95% CI)a
|81 (58, 95)||50 (28, 72)|
|Complete Response (%)||38||5|
|Duration of CNS Response|
|Number of Responders||17||11|
|CNS Response Duration ≥ 12 months (%)||59||36|
|a Clopper and Pearson exact binomial 95 percent confidence interval.|
IRC: independent review committee; CI: confidence interval; NE: not estimable
Grade ≥ 3 adverse reactions were reported for 41 percent of people treated with Alecensa. The most common Grade 3-4 adverse reactions (≥ 3 percent) were evidence of kidney dysfunction (increased creatinine; 4.1 percent), evidence of liver dysfunction (hyperbilirubinemia; 5 percent), low levels of sodium (hyponatremia; 6 percent), increased liver enzymes (aspartate transaminase; 6 percent, and alanine transaminase; 6 percent), and decreased red blood cells (anemia; 7 percent). Serious adverse reactions reported in ≥ 2 percent of people treated with Alecensa were pneumonia (4.6 percent) and renal impairment (3.9 percent).
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. Approximately 5 percent of people with NSCLC in the United States are ALK-positive. ALK-positive NSCLC is often found in younger people who have a light or non-smoking history.
About Genentech Access Solutions
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Alecensa is a kinase inhibitor approved for the treatment of people with anaplastic lymphoma kinase (ALK)-positive metastatic non-small cell lung cancer (NSCLC) as detected by an FDA-approved test.
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
Kidney problems. Alecensa may cause severe or life-threatening kidney problems. Tell your healthcare provider right away if you have a change in the amount or color of your urine, or if you get new or worsening swelling in your legs or feet.
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
- 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:
- Swelling in hands, feet, ankles, and eyelids
- Low red blood cell count
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.
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.