FDA Approves Orkambi (lumacaftor/ivacaftor) for Cystic Fibrosis

ORKAMBI

Generic Name: ivacaftor and lumacaftor
Date of Approval: July 2, 2015
Company: Vertex Pharmaceuticals Incorporated

Treatment for: Cystic Fibrosis

July 2, 2015 — The U.S. Food and Drug Administration today approved the first drug for cystic fibrosis directed at treating the cause of the disease in people who have two copies of a specific mutation.

Orkambi (lumacaftor 200 mg/ivacaftor 125 mg) is now approved to treat cystic fibrosis (CF) in patients 12 years and older, who have the F508del mutation, which causes the production of an abnormal protein that disrupts how water and chloride are transported in the body. Having two copies of this mutation (one inherited from each parent) is the leading cause of CF.

“The FDA encourages manufacturers to develop new and innovative treatments for serious rare diseases like cystic fibrosis,” said John Jenkins, M.D., director of the Office of New Drugs, Center for Drug Evaluation and Research. “Today’s approval significantly broadens the availability of targeted treatments for the specific defects that cause cystic fibrosis.”

Orkambi received FDA’s breakthrough therapy designation because the sponsor demonstrated through preliminary clinical evidence that the drug may offer a substantial improvement over available therapies. The FDA also reviewed Orkambi under the priority review program. A priority review is conducted over six months, or less, instead of the standard 10 months, and is employed for drugs that may offer significant improvement in safety or effectiveness in treatment over available therapy in a serious disease or condition.

In addition, the FDA granted Orkambi orphan drug designation because it treats cystic fibrosis, a rare disease. Orphan drug designation provides financial incentives, like clinical trial tax credits, user fee waivers, and eligibility for market exclusivity to promote rare disease drug development.

CF is a serious genetic disorder that results in the formation of thick mucus that builds up in the lungs, digestive tract and other parts of the body leading to severe respiratory and digestive problems, as well as other complications such as infections and diabetes.

CF, which affects about 30,000 people in the United States, is the most common fatal genetic disease in Caucasians. The F508del mutation is the most common cause of CF. People who have two copies of the F508del mutation, one inherited from each parent, account for approximately half of the CF population in the U.S.

The safety and efficacy of Orkambi was studied in two double-blind, placebo-controlled clinical trials of 1,108 participants with CF who were 12 years and older with the F508del mutation. In both studies, participants with CF who took Orkambi, two pills taken every 12 hours, demonstrated improved lung function compared to those who took placebo.

The efficacy and safety of Orkambi have not been established in patients with CF other than those with the F508del mutation. If a patient’s genotype is unknown, an FDA cleared CF mutation test should be used to detect the presence of the F508del mutation on both alleles of the CFTR gene.

The most common side effects of Orkambi include shortness of breath, upper respiratory tract infection, nausea, diarrhea, and rash. Women who took Orkambi also had increased menstrual abnormalities such as increased bleeding.

PATIENT INFORMATION

Read this Patient Information before you start treatment and each time you get a refill. There may be new information. This information does not take the place of talking with your doctor about your medical condition or your treatment.

WHAT IS ORKAMBI?

Orkambi is a prescription medicine used for the treatment of cystic fibrosis (CF) in patients age 12 years and older who have two copies of the F508del mutation (F508del/F508del) in their CFTR gene. It should not be used in patients other than those who have two copies of theF508del mutation in their CFTR gene.It is not known if this medicine is safe and effective in children under 12 years of age.

WHO SHOULD NOT TAKE ORKAMBI?

Do not take Orkambi if you take certain medicines or herbal supplements such as:

• antibiotics: rifampin (Rifamate, Rifater) or rifabutin (Mycobutin)
• seizure medications: phenobarbital, carbamazepine (Tegretol, Carbatrol, and Equetro), or phenytoin (Dilantin, Phenytek)
• sedatives/anxiolytics: triazolam (Halcion) or midazolam (Dormicum, Hypnovel, and Versed)
• immunosuppressant medicines: everolimus (Zortress), sirolimus (Rapamune), or tacrolimus (Astagraf XL, Envarsus XR, Prograf, Protopic)
• St. John’s wort (Hypericum perforatum)

Talk to your doctor before you start treatment if you take any of the medicines or supplements listed above.

WHAT SHOULD I TELL MY DOCTOR?

Before you start treatment, tell your doctor if you:

• have or have had liver problems
• have kidney problems
• are using birth control (hormonal contraceptives, including oral, injectable, transdermal, or implantable forms). Hormonal contraceptives should not be used as a method of birth control when taking Orkambi. Talk to your doctor about the best birth-control method you should use.
• are pregnant or plan to become pregnant. It is not known if this medicine will harm your unborn baby. You and your doctor should decide if you will take Orkambi while you are pregnant.
• are breastfeeding or planning to breastfeed. It is not known if this medicine passes into your breast milk. You and your doctor should decide if you will take Orkambi while you are breastfeeding.

Orkambi may affect the way other medicines work, and vice versa. Tell your doctor about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements, because the dose of Orkambi may need to be adjusted when taken with certain medications.

Ask your doctor or pharmacist for a list of these medicines if you are not sure.

Especially tell your doctor if you take:

• antifungal medications such as ketoconazole (Nizoral), itraconazole (Sporanox), posaconazole (Noxafil), or voriconazole (Vfend)
• antibiotics such as telithromycin (Ketek), clarithromycin (Biaxin), or erythromycin (Ery-Tab)

Know the medicines you take. Keep a list of them to show your doctor and pharmacist when you get a new medicine.

HOW SHOULD I TAKE ORKAMBI?

• Take Orkambi exactly as your doctor tells you to take it.
• Always the tablets with fat-containing foods such as eggs, avocados, nuts, butter, peanut butter, cheese pizza, whole-milk dairy products, (such as whole milk, cheese, and yogurt), etc.
• Take your doses twelve hours apart.
• Each box contains four weekly cartons. Each carton contains seven daily blister strips. Each blister strip contains four tablets so you can take two tablets for the morning and two tablets for the evening.
• You may cut along the dotted line to separate your morning dose from your evening dose.
• Unpeel the paper backing from a blister strip to remove two tablets and take them with fat-containing food in the morning, and repeat again in the evening, twelve hours later.
• If you miss a dose within six hours of when you usually take it, take your dose with fat-containing food as soon as possible.
• If you miss a dose and it is more than six hours after the time you usually take it, skip that dose only and take the next dose when you usually take it. Do not take two doses at the same time to make up for your missed dose.
• Tell your doctor if you stop treatment for more than one week. Your doctor may need to change your dose of Orkambi or other medicines you take.

WHAT SHOULD I AVOID WHILE TAKING ORKAMBI?

It is unknown if Orkambi causes dizziness. Do not drive a car, use machinery, or do anything that needs you to be alert until you know how it affects you.

ORKAMBI SIDE EFFECTS

Orkambi can cause serious side effects.

High liver enzymes in the blood, which can be a sign of liver injury, have been reported in patients receiving Orkambi.

Your doctor will do blood tests to check your liver:

• before you start treatment
• every three months during your first year of treatment
• every year while you are taking Orkambi

Call your doctor right away if you have any of the following symptoms of liver problems:

• pain or discomfort in the upper right stomach (abdominal) area
• yellowing of your skin or the white part of your eyes
• loss of appetite
• nausea or vomiting
• dark, amber-colored urine
• confusion

Respiratory events such as shortness of breath or chest tightness were observed in patients when starting Orkambi. If you have poor lung function your doctor may monitor you more closely when you start treatment.

Abnormality of the eye lens (cataract) has been noted in some children and adolescents receiving ivacaftor, a component of Orkambi. Your doctor should perform eye examinations prior to and during treatment to look for cataracts.

The most common side effects include:

• shortness of breath and/or chest tightness
• upper respiratory tract infection (common cold), including sore throat, stuffy or runny nose
• gastrointestinal symptoms, including nausea, diarrhea, or gas
• rash
• fatigue
• flu or flu-like symptoms
• increase in muscle enzyme levels
• irregular, missed, or abnormal periods (menses) and increase in the amount of menstrual bleeding

Tell your doctor if you have any side effect that bothers you or that does not go away.

These are not all the possible side effects. For more information, ask your doctor or pharmacist.

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

HOW SHOULD I STORE ORKAMBI?

• Store Orkambi at room temperature between 68°F to 77°F (20°C to 25°C).

Do not use Orkambi after the expiration date on the package.

Keep all medicines out of the reach of children.

GENERAL INFORMATION ABOUT THE SAFE AND EFFECTIVE USE OF ORKAMBI.

Medicines are sometimes prescribed for purposes other than those listed in a Patient Information leaflet. Do not use this medicine for a condition for which it was not prescribed. Do not give it to other people, even if they have the same symptoms you have. It may harm them.

This Patient Information summarizes only the most important information. If you would like more information, talk with your doctor. You can ask your pharmacist or doctor for information that is written for health professionals.

WHAT ARE THE INGREDIENTS IN ORKAMBI?

Active ingredients: lumacaftor and ivacaftor

Inactive ingredients: cellulose, microcrystalline; croscarmellose sodium; hypromellose acetate succinate; magnesium stearate; povidone; and sodium lauryl sulfate.

The tablet film coat contains: carmine, FD&C Blue #1, FD&C Blue #2, polyethylene glycol, polyvinyl alcohol, talc, and titanium dioxide.

The printing ink contains: ammonium hydroxide, iron oxide black, propylene glycol, and shellac.