FDA Approves COTELLIC™ (Cobimetinib) for use in Combination with Vemurafenib to Treat Advanced Melanoma
COTELLIC is expected to be available in the U.S. within two weeks –
--U.S. Profit Share Arrangement Will Provide Exelixis a Second Source of Product Revenue --
Genentech sponsored the COTELLIC U.S. New Drug Application (NDA), having
led the compound’s development since midway through the initial phase 1
clinical trial. Genentech filed its NDA in
“The approval of COTELLIC for use in combination with vemurafenib is an
important milestone for the melanoma community, and also for
The COTELLIC approval is based on data from the phase 3 coBRIM study, which showed COTELLIC plus vemurafenib reduced the risk of disease worsening or death (progression-free survival; PFS) by about half in people who received the combination (HR=0.56, 95 percent CI 0.45-0.70; p<0.001), with a median PFS of 12.3 months for COTELLIC plus vemurafenib compared to 7.2 months with vemurafenib alone. An interim analysis also showed the combination of COTELLIC and vemurafenib helped people live significantly longer (overall survival) than vemurafenib alone (HR=0.63, 95 percent CI 0.47-0.85; p=0.0019). The objective response rate (tumor shrinkage) was higher with COTELLIC plus vemurafenib compared to vemurafenib alone (70 vs. 50 percent; p<0.001), as was the complete response rate (complete tumor shrinkage, 16 vs. 10 percent).
Possible serious side effects with COTELLIC include risk of skin cancers, increased risk of bleeding, heart problems that can lead to inadequate pumping of the blood by the heart, rash, eye problems, abnormal liver test or liver injury, increased levels of an enzyme in the blood, and photosensitivity. The most common side effects of COTELLIC include diarrhea, sunburn or sun sensitivity, nausea, fever and vomiting. COTELLIC can also cause changes in blood test results.
The final overall survival analysis from the coBRIM trial will be
presented at the
Dr. Morrissey continued: “The approval of COTELLIC represents a major
About COTELLIC™ in Combination with Vemurafenib
COTELLIC™ (cobimetinib) is indicated for the treatment of patients with unresectable or metastatic melanoma with a BRAF V600E or V600K mutation, in combination with vemurafenib.
COTELLIC and vemurafenib are prescription medicines used in combination to treat 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. Found in approximately half of melanomas, mutated BRAF causes abnormal signaling inside cancer cells leading to tumor growth. Vemurafenib is designed to inhibit some mutated forms of BRAF and COTELLIC is designed to inhibit some forms of MEK. Both BRAF and MEK are proteins in a cell signaling pathway that help control cell growth and survival. When used in combination, COTELLIC and vemurafenib are thought to reduce cancer cell growth longer than with vemurafenib alone. A patient’s healthcare provider will perform a test to make sure COTELLIC and vemurafenib are right for the patient. It is not known if COTELLIC and vemurafenib are safe and effective in children under 18 years of age.
About Melanoma and its BRAF V600 Mutation-Positive Form
Melanoma is the less common, but more serious category of skin cancer
that starts in the skin’s pigment producing cells known as melanocytes.
According to the
COTELLIC™ Important Safety Information
Before taking COTELLIC, patients should tell their doctor if they:
- have any previous or current skin problems other than melanoma
- have any medical conditions and/or are on any medications that increase your risk of bleeding
- have any heart problems
- have any eye problems
- have any liver problems
- have any muscle problems
- have any other medical conditions
are pregnant or plan to become pregnant. COTELLIC can harm an unborn
- Patients who take COTELLIC should use effective methods of birth control during treatment, for at least two weeks after stopping COTELLIC, and for at least two months after stopping vemurafenib.
- 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 or think they are pregnant during treatment with COTELLIC.
- are breastfeeding or plan to breastfeed. It is not known if COTELLIC passes into breast milk, so patients should not breastfeed during treatment with COTELLIC and for two 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 the medicines they take, including prescription and over-the-counter medicines, vitamins and herbal supplements because some types of medicines will make COTELLIC more harmful or less effective. Patients should know the medicines they take and keep a list of them to show their healthcare provider and pharmacist when they get a new medicine.
Patients should avoid sunlight while taking COTELLIC. COTELLIC can make patients’ skin sensitive to sunlight and cause them to 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.
COTELLIC may cause serious side effects, including:
- Risk of skin cancers. COTELLIC may cause skin cancers (cutaneous squamous cell carcinoma, keratoacanthoma or basal cell carcinoma).
Patients must check their skin and tell their doctor right away about any skin changes, including:
- 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 COTELLIC and every two months while taking COTELLIC. A patient’s healthcare provider may continue to check their skin for six months after they stop taking COTELLIC.
Increased risk of bleeding. COTELLIC may cause bleeding,
including blood in the urine, rectal bleeding, unusual or excessive
vaginal bleeding, bleeding of the gums and bleeding within the brain
A patient should tell their healthcare provider right away if they experience any of these symptoms:
- red or black stools that look like tar
- blood in the urine
- headache, dizziness or feeling weak
- abdominal pain
- unusual vaginal bleeding
Heart problems that can lead to inadequate pumping of the
blood by the heart. A patient’s healthcare provider should perform
tests before the patient starts taking COTELLIC and during a patient’s
treatment with COTELLIC to check the ability of the heart to pump
blood. Signs and symptoms of a decrease in the amount of blood pumped
- persistent coughing or wheezing
- shortness of breath
- swelling of their ankles and feet
- increased heart rate
Rash. Patients should tell their healthcare provider right away
if they experience any of these symptoms:
- a rash that covers a large area of their body, blisters or peeling skin
Eye problems. Patients should tell their healthcare provider
right away if they experience any of these symptoms during treatment
- blurred vision
- distorted vision
- partly missing vision
any other vision changes
Some of these eye problems may be a result of something called “serous retinopathy” (a build-up of fluid under the retina of the eye). A patient’s healthcare provider should check their eyes if they notice any of the symptoms above.
Abnormal liver test or liver injury. A patient’s healthcare
provider should perform blood tests before the start taking COTELLIC,
and during treatment. A patient should tell their healthcare provider
right away if you experience any of these symptoms:
- yellowing of their skin or the white of their eyes
- dark or brown (tea color) urine
- nausea or vomiting
- feeling tired or weak
- loss of appetite
Increased levels of an enzyme in the blood. Creatine
phosphokinase (CPK) is an enzyme that is primarily found in the
muscle, heart and brain. Treatment with COTELLIC may increase the
level of this enzyme in your blood and be a sign of muscle damage. A
patient’s healthcare provider should perform a blood test before and
during treatment. Increased blood levels of CPK can also be an
indication of a serious condition caused by injury to the muscles
(rhabdomyolysis). A patient should tell their healthcare provider
right away if they experience any of these symptoms:
- muscle aches
- muscle spasms and weakness
- dark, reddish urine
Photosensitivity. A patient’s skin may become more sensitive to
sunlight while taking COTELLIC. A patient should tell their healthcare
provider if they notice any of the following symptoms:
- red, painful, itchy skin that is hot to touch
- sun rash
- skin irritation bumps or tiny papules
- thicken, dry, wrinkled skin
The most common side effects of COTELLIC include:
- sunburn or sun sensitivity
A patient’s healthcare provider will take blood tests while they are taking COTELLIC. The most common changes to blood tests include:
- increased blood levels of liver enzymes (GGT, ALT or AST)
- increased blood level of enzyme from muscle (creatine phosphokinase)
- decreased blood level of phosphate, sodium or potassium
- increased blood level of liver or bone enzyme (alkaline phosphatase)
- decreased blood level of a type of white blood cell (lymphocyte)
Patients should tell their healthcare provider if they have any side effect that bothers them or that does not go away.
These are not all the possible side effects of COTELLIC. 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 should talk to their doctor for medical advice about side
effects. Report side effects to
Please see full COTELLIC Prescribing Information and Patient Information for additional important safety information.
Forward-Looking Statement Disclaimer
This press release contains forward-looking statements, including,
without limitation, statements related to: the potential for regulatory
approval for cobimetinib by the
Susan Hubbard, 650-837-8194
Investor Relations and Corporate Communications
For Exelixis, Inc.
Hal Mackins, 415-994-0040