The Road to Orkambi

You may have heard that there is a new medication for people with a certain gene mutation of Cystic Fibrosis.

The FDA has approved a new drug that treats patients with two copies of the most common gene mutation, Delta f508. Forty-five percent of CF patients fit this profile.

The Basics of the Cystic Fibrosis Gene Mutation

Each of the more than 1,500 known mutations affects protein responsible for the proper transport of salt and water through each cell, creating a thick, sticky mucus that clogs the lungs and digestive system. Each of those mutations in the CFTR (transmembrane conductance regulator) protein has a different faulty mechanism.

Think of the protein as an electronic garage door. Consider some ways in which the door can malfunction:

  • The door doesn’t open or open all the way to allow the car to drive through.
  • The door doesn’t close or close all the way when the car is inside the garage.
  • The door folds or crumples while the car is driving into the garage.
  • The door opens erratically and unexpectedly.
  • The door is too narrow for the car to pass through.
  • The door is too weak or thin to protect the car inside the garage.
  • The signal from the remote control doesn’t work.
  • The door doesn’t exist at all.

What’s Different about Orkambi?

Historically, treatments focus on managing the symptoms of CF, especially lung infections and digestive problems. While these treatments can slow down the progression of the disease, it does not treat the root cause. The Delta f508 mutation occurs because of the deletion of one of the building blocks of the protein.

Orkambi, created by Boston-based Vertex pharmaceuticals, basically fixes the malfunction.

Orkambi is a combination of two medications:

  1. Lumacaftor – corrects the protein malfunction, also known as VX-809.
  2. Ivacaftor – goes by the trade name Kalydeco and also known as VX-770. Increases the sensitivity of the protein to enhancement. Kalydeco was originally developed to help treat a less-frequent mutation G551D, which affects about 4% of CF patients.

Patients who participated in all phases of the FDA trials continue to have access to Orkambi, and is now available the rest of the double Delta f508 population in the United States. Seventy percent of US patients have at least one copy of Delta f508.

Official and Anecdotal Results

There is much excitement around the approval of Orkambi.

The Facts

Hard evidence such as the FDA studies have only shown an average 4% in the increase of Lung Function (specifically, the measurement of FEV1, the amount of air that a patient can exhale in one second), but boasted a 30-39% decrease in the number of lung infections and need for antibiotic therapy.

Given that the biggest burden for many CF patients is the frequency and severity of lung infections, requiring strong antibiotic courses (often via IV and requiring hospitalization), and the ultimate destruction of healthy lung tissue, even a minor improvement in length, severity and frequency of flareups is still something.

Side effects led to 7% of participants to leave studies and discontinue taking the medication. Some patients reported lung tightness and shortness of breath, respiratory infections, GI issues such as diarrhea, gas and nausea, fatigue, and other symptoms.

Additional Benefits

Anecdotal information suggests that Orkambi can improve appetite, therapeutic weight gain (many CF patients are clinically underweight and suffer from malnutrition), decreased need for supplemental digestive enzymes (85% of CF patients are pancreatic insufficient), and lessening of severity of CF related diabetes.

The Bottom Line

Orkambi is a pill taken twice a day, and must be taken with high-fat food. It is approved for patients 12 and over in the United States. I’ve observed the first influx of patients filling their prescriptions with great enthusiasm. Countless others are in the process of meeting with their doctors, obtaining prescriptions, and seeking insurance coverage.

Which brings me to the most provocative of issues. The cost of one year of Orkambi is $259,000 a year. CF patients and specialty physicians have publicly decried the prohibitive cost of Orkambi.

CF patients aren’t new to the high cost prescription game. The annual cost of several of my medications is in the range of $30,000 each. Thankfully, we have health insurance, and some manufacturers provide patient assistance programs. Still, we spend considerable amount on medication, doctor, and hospital insurance fees, deductibles and copays.

However, I’ve read accounts of a number of patients whose insurance plans specifically exclude coverage of Orkambi, haven’t made coverage decisions yet (which may delay official decisions by months or even years), or are dragging patients through the rejection and appeals processes.

Here is Vertex’s statement on the cost assistance programs for Orkambi:

Vertex also offers a co-pay assistance program for patients with commercial insurance coverage and a free medicine program for qualifying patients who are uninsured and who meet certain income criteria and other eligibility criteria. More information is available by visiting or calling 1-877-752-5933.

I have done a lot of research on Orkambi, and plan to discuss it with my doctor at my next visit. I admit that I am already dreading the insurance process, as I have been fighting with my insurance provider over several of my necessary maintenance medications that cost much less than Orkambi. I worry that the amount of work it may take, the potential for side effects, and the cost to my insurance company will outweigh the benefits to my taking Orkambi.

As I am in the middle of a lung flareup and feel pretty awful, however, I’ve warmed up to the idea of trying Orkambi to perhaps deliver the most mild benefits. Fewer exacerbations and hospitalizations would be a huge blessing. I usually get (newly) sick every 6-8 weeks, and in the past 12 months have had 4 hospitalizations. I love the idea of not getting sick so often, as well as the possibility of improvement of my GI issues.

My next step is talking to my Cystic Fibrosis doctors. I’ll update you after that happens.


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