Monday, Aug 7, 2017

FDA Grants Priority Review and Breakthrough Therapy Designation for Zelboraf (vemurafenib) in Erdheim-Chester Disease with BRAF V600 Mutation

There are currently no FDA-approved treatments for Erdheim-Chester disease (ECD), a rare blood disease

VE-BASKET study enrolled participants across multiple diseases, based predominantly on genetic profile

South San Francisco, CA -- August 7, 2017 --

Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY), today announced that the U.S. Food and Drug Administration (FDA) has accepted the company’s supplemental New Drug Application (sNDA) and granted Priority Review for Zelboraf^® (vemurafenib) for Erdheim-Chester disease (ECD) with BRAF V600 mutation. ECD is a rare, serious blood disease characterized by the abnormal multiplication of certain white blood cells called histiocytes. Zelboraf was also granted Breakthrough Therapy Designation (BTD) by the FDA for this indication. The FDA is expected to make a decision on approval by December 7, 2017.

The sNDA includes data from the open-label, Phase II VE-BASKET study. Basket studies use an innovative clinical trial design that helps collect data faster and may accelerate the development of medicines for diseases with high unmet need. Instead of enrolling people based primarily on their disease or its location, basket studies match a disease’s underlying genetic profile to the mechanism of action of the medicine. This allows researchers to evaluate multiple diseases simultaneously. This is particularly important for diseases that are extremely rare, making it difficult to fully enroll a disease- or tumor-specific trial.

“This first potential treatment submitted to the FDA for this rare disease was identified by an innovative trial studying Zelboraf across different diseases with the same genetic mutation,” said Sandra Horning, M.D., chief medical officer and head of Global Product Development. “We are committed to bringing new treatment options to people with rare diseases and hope to see Zelboraf approved for Erdheim-Chester disease as soon as possible.”

A Priority Review designation is granted to medicines that the FDA has determined to have the potential to provide significant improvements in the treatment, prevention or diagnosis of a disease. 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. This is the sixteenth Breakthrough Therapy Designation granted to Genentech medicines since 2013 – the most of any company in the industry.

About the VE-BASKET Study

VE-BASKET is a Phase II, non-randomized, basket study investigating the use of Zelboraf for people with BRAF V600 mutation-positive cancers and other diseases, including ECD. Final results for the 22 people with ECD showed a best overall response rate of 54.5 percent by RECIST v1.1. The median duration of response, progression-free survival and overall survival were not reached at a median follow-up time of 26.6 months. The most common adverse events were joint pain, rash, hair loss, change in heart rhythm, fatigue, skin tags, diarrhea and thickening of the skin. The most common Grade 3 or higher adverse events were new skin cancers, high blood pressure, rash and joint pain. Initial study results were published in the New England Journal of Medicine in August 2015.

About Erdheim-Chester Disease

Erdheim-Chester disease (ECD) is an extremely rare non-Langerhans cell histiocytosis. The exact prevalence and incidence of ECD are difficult to ascertain given the disease is so rare. Based on available published data, it’s estimated there are fewer than 500 cases of ECD in the United States. More than 50 percent of people with ECD have BRAF V600 mutation-positive disease. No large studies have been performed and there are currently no approved treatments for ECD.

About Zelboraf

Zelboraf is designed to inhibit some mutated forms of BRAF, which cause abnormal signaling inside cancer cells leading to tumor growth. BRAF is a protein in a cell signaling pathway that helps control cell growth and survival. Zelboraf was the first approved product in its class. Zelboraf was co-developed under a 2006 license and collaboration agreement between Roche and Plexxikon, now a member of the Daiichi Sankyo Group.

Zelboraf Indication

Zelboraf is a prescription medicine used to treat a type of skin cancer called melanoma that has spread to other parts of the body or cannot be removed by surgery, and that has a certain type of abnormal “BRAF” gene.

A patient’s healthcare provider will perform a test to make sure that Zelboraf is right for them.

Zelboraf is not used to treat melanoma with a normal BRAF gene. It is not known if Zelboraf is safe and effective in children under 18 years of age.

Important Safety Information

What is the most important information patients should know about Zelboraf?

Zelboraf can cause serious side effects, including:

• Risk of cancers. Zelboraf may cause a type of skin cancer called cutaneous squamous cell carcinoma (cuSCC). New melanoma lesions have occurred in people who take Zelboraf. Zelboraf may also cause another type of cancer called non-cutaneous squamous cell carcinoma (SCC). Patients should talk with their healthcare provider about their risk for these cancers.

Patients should check their skin and tell their healthcare provider right away about any skin changes, including a:

• new wart
• skin sore or reddish bump that bleeds or does not heal
• change in size or color of a mole

A patient’s healthcare provider should check their skin before they start taking Zelboraf, and every 2 months while they are taking Zelboraf, to look for any new skin cancers. A patient’s healthcare provider may continue to check their skin for 6 months after they stop taking Zelboraf.

A patient’s healthcare provider should also check for cancers that may not occur on the skin. Patients should tell their healthcare provider about any new symptoms that they get while taking Zelboraf.

What should patients tell their healthcare provider before taking Zelboraf?

Before patients take Zelboraf, they should tell their healthcare provider if they:

• Have any heart problems, including a condition called long QT syndrome
• Have liver or kidney problems
• Have had or are planning to receive radiation therapy
• Have been told that they have low blood levels of potassium, calcium, or magnesium
• Have any other medical conditions
• Are pregnant or plan to become pregnant. Zelboraf can harm an unborn baby.
  • Females who are able to become pregnant should use effective birth control during Zelboraf treatment and for 2 weeks after the final dose 
  • Patients should talk to their healthcare provider about birth control methods that may be right for them
  • Patients should tell their healthcare provider right away if they become pregnant during treatment with Zelboraf

• Are breastfeeding or plan to breastfeed. It is not known if Zelboraf passes into breast milk. Patients should not breastfeed during treatment with Zelboraf and for 2 weeks after the final dose. Patients should talk to their healthcare provider about the best way to feed their baby during this time.

Patients should tell their healthcare provider about all of the medicines they take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. Patients should know the medicines they take. Patients should keep a list of them to show their healthcare provider and pharmacist when they get a new medicine.

What should patients avoid while taking Zelboraf?

Patients should avoid sunlight while they are taking Zelboraf. Zelboraf can make a patient’s skin sensitive to sunlight. Patients may burn more easily and get severe sunburns. To help protect against sunburn:

• When patients go outside, they should wear clothes that protect their skin, including their head, face, hands, arms, and legs.
• Patients should use lip balm and a broad-spectrum sunscreen with SPF 30 or higher.

What are the possible side effects of Zelboraf?

• Allergic reactions can happen while taking Zelboraf, and can be severe. Patients should stop taking Zelboraf and get medical help right away if they get any of these symptoms of an allergic reaction:
  • Rash or redness all over their body
  • Trouble breathing or swallowing
  • Swelling of the face, lips, or tongue
  • Throat tightness or hoarseness
  • Feel faint
  • Fast heartbeat
• Severe skin reactions. Patients should stop taking Zelboraf and call their healthcare provider right away if they get a skin rash with any of the following symptoms, because they may have a severe skin reaction:
  • Blisters on their skin
  • Blisters or sores in their mouth
  • Peeling of their skin
  • Fever
  • Redness or swelling of their face, hands, or soles of their feet
• Changes in the electrical activity of the heart called QT prolongation. QT prolongation can cause irregular heartbeats that can be life-threatening. A patient’s healthcare provider should do tests before they start taking Zelboraf and during treatment with Zelboraf to check the electrical activity of their heart. Patients should tell their healthcare provider right away if they feel faint, lightheaded, dizzy, or feel their heart beating irregularly or fast while taking Zelboraf. These may be symptoms related to QT prolongation.
• Liver injury. A patient’s healthcare provider should do blood tests to check their liver function before they start taking Zelboraf and during treatment. Patients should tell their healthcare provider right away if they get any of these symptoms of a liver problem during treatment:
  • Yellowing of their skin or the white part of their eyes
  • Dark or brown (tea color) urine
  • Nausea or vomiting
  • Loss of appetite
  • Pain on the right side of their stomach
• Eye problems. Patients should tell their healthcare provider right away if they get any of these symptoms during treatment with Zelboraf:
  • Eye pain, swelling, or redness
  • Blurred vision or other vision changes
• Worsening side effects from radiation treatment. Patients should tell their healthcare provider if they have had or are planning to receive radiation therapy.
• Kidney injury. A patient’s healthcare provider should do blood tests to check their kidney function before they start taking Zelboraf and during treatment.

The most common side effects include:

• Joint pain
• Rash
• Hair loss
• Tiredness
• Sunburn or sun sensitivity
• Nausea
• Itching
• Warts

Patients should tell their healthcare provider if they have any side effect that bothers them or does not go away. These are not all of the possible side effects of Zelboraf. For more information about side effects, patients should ask their healthcare provider or pharmacist. Patients should call their doctor for medical advice about side effects.

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

Please see Full Prescribing Information and Medication Guide for additional Important Safety Information at http://www.zelboraf.com .

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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