Vertex: The FDA Advisory Committee Recommended Approval for Orkambi

AS WE AND PREDICTED, the FDA Pulmonary-Allergy Drugs Advisory Committee (PADAC), voted in favor of approving Vertex’s (VRTX) drug Orkambi™ (lumacaftor/ivacaftor) for people with Cystic Fibrosis (CF) ages 12 and older who have two copies of the F508del mutation in the CFTR gene. The FDA is expected to make a decision on the approval of Orkambi by July 5, 2015 under the Prescription Drug User Fee Act (PDUFA).  

If approved, Orcambi will be the second treatment in Vertex’s cystic fibrosis program to reach the market, expanding it. Orkambi will also be the only drug to treat the underlying cause of CF for eligible people with CF ages 12 and older with two copies of the F508del mutation in the CFTR gene. Vertex is now testing the drug in children as young as 6.

Orcambi will also be the second cystic fibrosis drug for Vertex that aims at repairing a gene’s defective proteins, which is at the origin of CF, rather than only treating the symptoms, which arise from the complications of the disease. The first product to act on the root-cause of CF is Kalydeco, which is also designed and developed by Vertex and the Cystic Fibrosis Foundation Therapeutics, Inc. (CFFT).

Vertex initiated its CF research program in 1998 as part of a collaboration with Cystic Fibrosis Foundation Therapeutics (CFFT), the nonprofit drug discovery and development affiliate of the Cystic Fibrosis Foundation. This collaboration was expanded to support the accelerated discovery and development of Vertex’s CFTR modulators.

The market for Kalydeco is small with 2000 patients and that of Orkambi is much larger estimated at 8,500 people.

In our article posted yesterday under Today’s Highlights at we mentioned that the FDA informed the advisory committee that Orkambi has shown to improve lung function by a maximum of 3 percentage points only compared to placebo. We felt confident, though, that, although the members of the advisory committee might consider this fact in their discussions, the drug will be approved based on the trial results that were considered statistically significant for CF.

The debate of the advisory committee’s members was fierce and demanded several hours before the committee finally votes in favor of approval. The discussions revolved around the FDA suggestion that Orkambi’s effect on lung function might not be much greater than that of ivacaftor alone for the patients with the two copies of the F508del mutation in the CFTR gene. This suggestion raised questions about whether the second drug lumacaftor is really adding efficacy to that offered by Kalydeco. During the meeting, Vertex reminded that the FDA had agreed to trials that would not compare Orkambi to its components, only to a placebo, as earlier studies had demonstrated that neither drug alone worked.

After the long debate, during which time the committee was split on whether lumacaftor really added to the efficacy, they finally decided that it did not really matter as long as the combination did the job without safety concerns from the combination.

What about following the FDA approval, which is expected?

Regarding the price: We believe that it will be less than that of Kalydeco’s price tag. We do not see any challenge by the third party payers, as CF is a rare, life-threatening genetic disease where the median predicted age of survival is between 34 and 47 years, but the median age of death remains in the mid-20s.

Regarding Orcambi’s sales: We do not believe that the people ages 12 and older with two copies of the F508del mutation in the CFTR gene represent all the 8,500 people in this category. Children age 6 to 12 are still being tested for safety and efficacy and are not yet considered eligible for taking Orcambi until the ongoing trial results are announced. Additionally, not all the patients with the two copies of the F508del mutation will continue taking Orcambi in case the drug fails to help them breathe.

Around 75,000 people in North America, Europe and Australia suffer from CF and are threatened to die at a young age. There are more than 1,900 known mutations in the CFTR gene. Some of these mutations lead to CF by creating malfunctioned or few CFTR proteins at the cell surface. The defective or missing CFTR protein results in poor flow of salt and water into and out of the cell in a number of organs, including the lungs. This leads to the buildup of abnormally thick, sticky mucus that can cause chronic lung infections and progressive lung damage, eventually leading to death.

We believe Vertex is in a unique position to reverse the bad prognosis of CF. The firm has unique technology and expertise to advance its CF treatment, which works at the root-cause of the disease. It has already an approved drug, Kalydeco for a mutation that affects a small number of patients and another drug, Orkambi, which is on its way to be marketed soon for a mutation that affects much larger population. Vertex will continue its research and development to save more and more, if not most of the 130,000 patients who suffer CF around the world.

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