FDA Grants Genentech’s TECENTRIQ (Atezolizumab) Accelerated Approval as Initial Treatment for Certain People with Advanced Bladder Cancer

– First and only cancer immunotherapy approved in advanced bladder cancer as initial treatment for those unable to receive cisplatin chemotherapy –

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) granted accelerated approval to TECENTRIQ^® (atezolizumab) for the treatment of people with locally advanced or metastatic urothelial carcinoma (mUC) who are not eligible for cisplatin chemotherapy. TECENTRIQ was previously approved for people with locally advanced or mUC who have disease progression during or following any platinum-containing chemotherapy, or within 12 months of receiving chemotherapy before surgery (neoadjuvant) or after surgery (adjuvant). It is not known if TECENTRIQ is safe and effective in children. Bladder cancer is the most common type of urothelial carcinoma, and up to half of all people with the advanced form of the disease are unable to receive cisplatin chemotherapy as an initial treatment and therefore have a high unmet medical need. Urothelial carcinoma also includes cancers of the urethra, ureters and renal pelvis.

“We are pleased that TECENTRIQ will now be available to more people with advanced bladder cancer, including those who are unable to receive initial treatment with cisplatin chemotherapy,” said Sandra Horning, M.D., chief medical officer and head of Global Product Development. “TECENTRIQ was the first cancer immunotherapy approved by the FDA for people with advanced bladder cancer and has become a standard of care in those whose disease has progressed after receiving other medicines, either before or after surgery, or after their disease has spread.”

“It is encouraging to see continued progress in the treatment of advanced bladder cancer, which until last year had not seen any major advancements in more than 30 years,” said Andrea Maddox Smith, chief executive officer, Bladder Cancer Advocacy Network. “We are excited that TECENTRIQ is now a treatment option for people with advanced bladder cancer who are unable to receive a cisplatin-based chemotherapy as an initial treatment.”

The FDA’s Accelerated Approval Program allows conditional approval of a medicine that fills an unmet medical need for a serious condition, based on early evidence suggesting clinical benefit. The indication for TECENTRIQ is approved under accelerated approval based on tumor response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials. Today’s approval of TECENTRIQ is based on the Phase II IMvigor210 study.

Possible serious side effects with TECENTRIQ include, but are not limited to, lung problems (pneumonitis), liver problems (hepatitis), intestinal problems (colitis), hormone gland problems (especially the pituitary, thyroid, adrenal glands and pancreas), nervous system problems (neuropathy, meningitis and encephalitis), eye problems (inflammation of the eyes), severe infections and severe infusion reactions. Additional information on these and other side effects can be found below.

For those who qualify, Genentech offers patient assistance programs for people taking TECENTRIQ through Genentech Access Solutions. Doctors can contact Genentech Access Solutions at [phone]. More information is also available at http://www.Genentech-Access.com.

This is the third approval for TECENTRIQ in under a year. TECENTRIQ is also approved for the treatment of people with metastatic non-small cell lung cancer (NSCLC) who have disease progression during or following platinum-containing chemotherapy, and have progressed on an appropriate FDA-approved targeted therapy if their tumor has EGFR or ALK gene abnormalities.

About the IMvigor210 study

IMvigor210 is an open-label, multicenter, single-arm Phase II study that evaluated the safety and efficacy of TECENTRIQ in people with locally advanced or mUC, regardless of PD-L1 expression. People in the study were enrolled into one of two cohorts. This accelerated approval is based on results from Cohort 1, which consisted of 119 people with locally advanced or mUC who were ineligible for cisplatin-containing chemotherapy and were either previously untreated or had disease progression at least 12 months after neoadjuvant or adjuvant chemotherapy. People in this cohort received a 1200-mg intravenous dose of TECENTRIQ every three weeks until either unacceptable toxicity or disease progression. The primary endpoint of the study was objective response rate (ORR).

A summary of the efficacy data from the IMvigor210 study that supports this accelerated approval is included below.

	All Patients	PD-L1 Expression Subgroups
	N=119	PD-L1 Expression of < 5% in ICs^1 (N=87)	PD-L1 Expression of ≥ 5% in ICs^1 (N=32)
Number of IRF- assessed Confirmed Responders	28	19	9
ORR %	23.5%	21.8%	28.1%
(95% CI)	(16.2, 32.2)	(13.7, 32.0)	(13.8, 46.8)
Complete Response (CR) (%)	6.7%	6.9%	6.3%
Partial Response (PR) (%)	16.8%	14.9%	21.9%
Median DoR, months (range)	NR (3.7, 16.6+)	NR (3.7, 16.6+)	NR (8.1, 15.6+)
IRF = Independent Review Facility NR = Not reached + Denotes a censored value ^1 PD-L1 expression in tumor-infiltrating immune cells (ICs)

The most common Grade 3-4 adverse reactions (≥ 2 percent) were: fatigue (8 percent), urinary tract infection (5 percent), anemia (7 percent), diarrhea (5 percent), increase in the level of creatinine in the blood (5 percent), intestinal obstruction (partial or complete blockage of the bowel), increase of the liver enzyme alanine transaminase (4 percent), hyponatremia (low blood sodium level; 15 percent), decreased appetite (3 percent), sepsis (blood infection), back/neck pain (3 percent), renal failure and hypotension (low blood pressure). Five people (4.2 percent) experienced either sepsis, cardiac arrest, myocardial infarction, respiratory failure or respiratory distress, which led to death. One additional patient (0.8 percent) experienced inflammation of the brain due to the herpes simplex virus (herpetic meningoencephalitis) and disease progression at the time of death. TECENTRIQ was discontinued for adverse reactions in 4.2 percent (5) of the 119 patients.

Genentech is evaluating TECENTRIQ in a confirmatory Phase III study (IMvigor211), which compares TECENTRIQ to chemotherapy as initial treatment in people with a specific type of advanced bladder cancer and in people whose bladder cancer has progressed on at least one prior platinum-containing regimen.

About metastatic urothelial cancer

According to the American Cancer Society (ACS), it is estimated that more than 79,000 Americans will be diagnosed in 2017 with bladder cancer, which is the most common type of urothelial cancer. Less common forms include cancers of the urethra, ureters and renal pelvis. About 11 percent of new diagnoses of bladder cancer are made when the disease is in advanced stages. There is a dramatic difference in survival rates between early and advanced bladder cancer. Approximately 96 percent of people will live five or more years when diagnosed with the earliest stage of the disease, compared to 39 percent when diagnosed in advanced stages (stage III-IV) of the disease. Men are about three to four times more likely to get bladder cancer during their lifetime than women.

About Genentech Access Solutions

Access Solutions is part of Genentech’s commitment to helping people access the Genentech medicines they are prescribed, regardless of their ability to pay. The team of in-house specialists at Access Solutions is dedicated to helping people navigate the access and reimbursement process, and to providing assistance to eligible patients in the United States who are uninsured or cannot afford the out-of-pocket costs for their medicine. To date, the team has helped more than 1.4 million patients access the medicines they need. Please contact Access Solutions (866) 4ACCESS/[phone] or visit http://www.Genentech-Access.com for more information.

About TECENTRIQ^® (atezolizumab)

TECENTRIQ is a monoclonal antibody designed to bind with a protein called PD-L1. TECENTRIQ is designed to bind to PD-L1 expressed on tumor cells and tumor-infiltrating immune cells, blocking its interactions with both PD-1 and B7.1 receptors. By inhibiting PD-L1, TECENTRIQ may enable the activation of T cells. TECENTRIQ may also affect normal cells.

TECENTRIQ U.S. Indication (pronounced ‘tē-SEN-trik’)

TECENTRIQ is a prescription medicine used to treat:

a type of bladder and urinary tract cancer called urothelial carcinoma.

• TECENTRIQ may be used when your bladder cancer:
  • has spread or cannot be removed by surgery (advanced urothelial carcinoma), and
  • you are not able to take chemotherapy that contains a medicine called cisplatin, or
  • you have tried chemotherapy that contains platinum, and it did not work or is no longer working.
    
    The approval of TECENTRIQ in these patients is based on a study that measured response rate and duration of response. There is an ongoing study to confirm clinical benefit.

a type of lung cancer called non-small cell lung cancer (NSCLC)

• TECENTRIQ may be used when your lung cancer:
  • has spread or grown, and
  • you have tried chemotherapy that contains platinum, and it did not work or is no longer working.
    
    If your tumor has an abnormal EGFR or ALK gene, you should have also tried an FDA-approved therapy for tumors with these abnormal genes, and it did not work or is no longer working.

It is not known if TECENTRIQ is safe and effective in children.

Important Safety Information

Important Information About TECENTRIQ

TECENTRIQ can cause the immune system to attack normal organs and tissues in many areas of the body and can affect the way they work. These problems can sometimes become serious or life-threatening and can lead to death.

Getting medical treatment right away may help keep these problems from becoming more serious. A healthcare provider may treat a patient with corticosteroid or hormone replacement medicines. A healthcare provider may delay or completely stop treatment with TECENTRIQ if a patient has severe side effects.

Patients should call or see their healthcare provider right away if they get any symptoms of the following problems or these symptoms get worse.

TECENTRIQ can cause serious side effects, including:

• Lung Problems (pneumonitis) – Signs and symptoms of pneumonitis may include: new or worsening cough, shortness of breath, or chest pain
• Liver Problems (hepatitis) – Signs and symptoms of hepatitis may include: yellowing of the skin or the whites of the eyes, severe nausea or vomiting, pain on the right side of the stomach area (abdomen), drowsiness, dark urine (tea colored), bleeding or bruising more easily than normal, feeling less hungry than usual
• Intestinal Problems (colitis) – Signs and symptoms of colitis may include: diarrhea (loose stools) or more bowel movements than usual, blood in the stools or dark, tarry, sticky stools, severe stomach area (abdomen) pain or tenderness
• Hormone Gland Problems (especially the pituitary, thyroid, adrenal glands and pancreas) – Signs and symptoms that the hormone glands are not working properly may include: headaches that will not go away or unusual headaches, extreme tiredness, weight gain or weight loss, dizziness or fainting, feeling more hungry or thirsty than usual, hair loss, changes in mood or behavior (such as decreased sex drive, irritability, or forgetfulness), feeling cold, constipation, voice gets deeper, urinating more often than usual, nausea or vomiting, stomach area (abdomen) pain
• Nervous System Problems (neuropathy, meningitis, encephalitis) – Signs and symptoms of nervous system problems may include: severe muscle weakness, numbness or tingling in hands and feet, fever, confusion, changes in mood or behavior, extreme sensitivity to light, neck stiffness
• Inflammation of the Eyes – Signs and symptoms may include: blurry vision, double vision, other vision problems, eye pain or redness
• Severe Infections – Signs and symptoms of infection may include: fever, cough, frequent urination, flu-like symptoms, pain when urinating
• Severe Infusion Reactions – Signs and symptoms of infusion reactions may include: chills or shaking, itching or rash, flushing, shortness of breath or wheezing, dizziness, fever, feeling like passing out, back or neck pain, and swelling of the face or lips

Before receiving TECENTRIQ, patients should tell their healthcare provider about all of their medical conditions, including if they:

• Have immune system problems (such as Crohn’s disease, ulcerative colitis, or lupus); have had an organ transplant; have lung or breathing problems; have liver problems; have a condition that affects their nervous system (such as myasthenia gravis, or Guillain-Barre syndrome); or are being treated for an infection
• Are pregnant or plan to become pregnant
  • TECENTRIQ can harm an unborn baby
  • If patients are able to become pregnant, they should use an effective method of birth control during treatment and for at least 5 months after the last dose of TECENTRIQ
• Are breastfeeding or plan to breastfeed
  • It is not known if TECENTRIQ passes into the breast milk
  • Do not breastfeed during treatment and for at least 5 months after the last dose of TECENTRIQ

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

The most common side effects of TECENTRIQ in people with urothelial carcinoma include:

• feeling tired
• decreased appetite
• nausea
• constipation
• urinary tract infection
• diarrhea
• fever

The most common side effects of TECENTRIQ in people with non-small cell lung cancer include:

• feeling tired
• decreased appetite
• shortness of breath
• cough
• nausea
• muscle or bone pain
• constipation

TECENTRIQ may cause fertility problems in females, which may affect the ability to have children. Patients should talk to their healthcare provider if they have concerns about fertility.

These are not all the possible side effects of TECENTRIQ. Patients should ask their healthcare provider or pharmacist for more information.

Report side effects to the FDA at 1-800-FDA-1088 or http://www.fda.gov/medwatch. Report side effects to Genentech at 1-888-835-2555.

Please visit http://www.Tecentriq.com for the TECENTRIQ full Prescribing Information for additional Important Safety Information.

About Genentech in Personalized Cancer Immunotherapy

For more than 30 years, Genentech has been developing medicines with the goal to redefine treatment in oncology. Today, we’re investing more than ever to bring personalized cancer immunotherapy (PCI) to people with cancer. The goal of PCI is to provide each person with a treatment tailored to harness his or her own immune system to fight cancer. Genentech is studying more than 20 investigational medicines, 10 of which are in clinical trials. In every study we are evaluating biomarkers to identify which people may be appropriate candidates for our medicines. For more information visit http://www.gene.com/cancer-immunotherapy.

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.