Orkambi (Lumacaftor/Ivacaftor) Film-coated Tablets

Orkambi is a combination therapy containing Lumacaftor and Ivacaftor, two drugs used to treat cystic fibrosis (CF) in patients aged two years and older who have two copies of the F508del mutation in their CFTR (cystic fibrosis transmembrane conductance regulator) gene. This mutation is the most common cause of cystic fibrosis, a hereditary condition that affects the lungs and digestive system due to the production of thick, sticky mucus. The therapy works by improving the function of the defective CFTR protein, helping to regulate the flow of salt and fluids in and out of cells, which in turn helps to thin the mucus. Orkambi helps manage the symptoms of cystic fibrosis, particularly targeting lung function and reducing the number of pulmonary exacerbations. Each Orkambi film-coated tablet contains:

• Lumacaftor (200 mg)
• Ivacaftor (125 mg)

How It Works

Orkambi works by addressing the underlying cause of cystic fibrosis in patients with the F508del mutation. This is a breakthrough approach compared to traditional treatments, which mainly manage symptoms without targeting the root cause.

Mechanism of Action:

1. Lumacaftor: Acts as a CFTR corrector. It helps correct the misfolding of the CFTR protein caused by the F508del mutation, allowing more of the CFTR protein to reach the cell surface where it can function properly.
2. Ivacaftor: A CFTR potentiator. Ivacaftor works by increasing the activity of the defective CFTR protein that has reached the cell surface. It keeps the protein’s channels open for longer, allowing chloride ions to flow through, which helps hydrate and thin the mucus in the lungs.

By working together, Lumacaftor and Ivacaftor help improve lung function and reduce mucus buildup, leading to fewer lung infections and better overall health for CF patients with the F508del mutation.

Side Effects

While Orkambi can improve the quality of life for cystic fibrosis patients, it may also cause side effects. Some side effects are mild, while others can be more serious and require medical attention.

Common Side Effects:

• Nausea: Feeling of discomfort in the stomach.
• Diarrhea: Frequent bowel movements or loose stools.
• Fatigue: General tiredness or lack of energy.
• Headache: Mild to moderate headaches are common.
• Shortness of Breath: Patients may experience difficulty breathing.
• Upper Respiratory Tract Infections: Increased susceptibility to infections.
• Chest Tightness: A sensation of pressure or discomfort in the chest.
• Rash: Some patients may develop skin reactions.

Serious Side Effects:

• Elevated Liver Enzymes: Orkambi may cause liver damage, especially in patients with pre-existing liver conditions.
• Serious Breathing Problems: Worsening of breathing difficulties may occur in some patients, particularly in the early stages of treatment.
• Increased Blood Pressure: Some patients may develop hypertension while on Orkambi.
• Abnormal Menstrual Cycles: In females, irregular periods or heavier menstrual bleeding may occur.

Patients are advised to undergo regular liver function tests while on Orkambi to monitor for potential liver toxicity.

Indications

Orkambi is specifically indicated for the treatment of cystic fibrosis in patients aged two years and older who have two copies of the F508del mutation in the CFTR gene. It is a targeted therapy designed to address the underlying genetic cause of cystic fibrosis in this particular population.

Approved Indications:

1. Cystic Fibrosis with F508del Mutation: Orkambi is used to treat patients who have the specific F508del mutation, as the combination of Lumacaftor and Ivacaftor works best in this genetic group.

Contraindications

Certain conditions or factors may preclude the use of Orkambi, or require careful monitoring.

Contraindications:

1. Severe Liver Impairment: Orkambi is contraindicated in patients with severe hepatic impairment, as it can exacerbate liver problems.
2. Hypersensitivity to Lumacaftor or Ivacaftor: Any patient with a known allergy or hypersensitivity to the active ingredients or excipients in Orkambi should avoid the medication.
3. CYP3A Inhibitors: The use of strong CYP3A inhibitors is contraindicated, as they can affect the metabolism of Ivacaftor, potentially leading to increased drug levels and adverse effects.

Price in Different Countries

The cost of Orkambi varies widely depending on the country and healthcare system. Below is a table showing the estimated price range for Orkambi in different regions. Please note that these prices are estimates and may change based on insurance coverage and pharmacy markups.

Country	Price (Per Month Supply)	Reference
United States	$25,000 – $30,000	GoodRx
United Kingdom	£10,000 – £12,000	NHS
Canada	CAD $20,000 – $25,000	Canada Pharmacy
Australia	AUD $20,000	PBS Australia
India	INR ₹18,00,000 – ₹22,00,000	1mg

Top 5 Global Brands

Orkambi is produced by Vertex Pharmaceuticals, a leader in the development of therapies for cystic fibrosis. Below are the top global pharmaceutical brands involved in the development of CF treatments and other respiratory therapies:

1. Vertex Pharmaceuticals

• The primary manufacturer of Orkambi and other breakthrough cystic fibrosis therapies, Vertex Pharmaceuticals is a pioneer in addressing genetic diseases.

2. Roche

• Roche is a global leader in developing respiratory therapies and has contributed to the development of diagnostic tools and treatments for cystic fibrosis.

3. Novartis

• Novartis has a strong presence in the respiratory field, offering treatments for lung-related conditions and other chronic diseases.

4. GlaxoSmithKline (GSK)

• GSK focuses on respiratory and immune-related diseases, developing inhalers and other treatments for cystic fibrosis and asthma.

5. Sanofi

• Sanofi is involved in the development of treatments for rare diseases, including genetic disorders like cystic fibrosis, and works on innovative drug therapies for chronic conditions.