Blog | Tuesday, March 27, 2012

Notes on Kalydeco, the new cystic fibrosis drug

I thought it worthwhile to learn a bit about Kalydeco, the new drug for cystic fibrosis. It's the first "smart" medication approved by the FDA for some patients with this condition. According to BusinessWeek and other sources, the annual cost of this oral treatment, manufactured by Vertex Pharmaceuticals, will be nearly $300,000.

Cystic fibrosis is an inherited disease that affects the lungs, sweat glands and, in males, the vas deferens, the tube that carries sperm from the testes. Patients are prone to infection (especially pneumonia), overheating, infertility and other problems.

Most symptoms arise from defects in transport of ions, like chloride, through membranes. Cystic fibrosis is often disabling and, typically, life-shortening. In 1989, Francis Collins and Lap-Chee Tsu reported in Science they'd discovered the gene responsible.

Now, there's a wealth of information about the Cystic Fibrosis Transmembrane Regulator (CFTR) gene. It's located on human chromosome 7 at q (long arm) 31.2, and encodes an ABC (ATP-binding cassette) type ion transporter protein. According to an analysis in Nature this week, scientists have identified over 1,500 CFTR mutations.

Kalydeco goes by the generic name ivacaftor and has been tested published reports as VX08-770–102. This compound targets the defect caused by one mutation, termed G551D. Only 4% of cystic fibrosis patients have this genetic variant. Over 90% have a different mutation, F508del. These distinct mutations alter the protein distinctly.

From Nature News: "... In patients with the G551D mutation, the channel fails to open properly, so ions are unable to pass through. About 90% of people with cystic fibrosis have a different mutation, called F508del, which results in proteins that do not fold into their proper shape and so get targeted for degradation, reducing the number of channels ..."

Drugs in the pipeline will target the more common F508del mutation. Meanwhile, it's easy to envision more than a few eager parents, patients and optimistic pediatricians wanting to prescribe the new drug for their cystic fibrosis patients who don't have the G551D mutation. The number of people living with cystic fibrosis in the U.S. is 30,000, according to the Cystic Fibrosis Foundation, so the FDA's approval applies to approximately 1,200 individuals, the 4% who carry the G551D mutation.

This seems a perfect example of a new, expensive drug that may really help just a few people, and for which there's a clear genetic marker. Now, if we could only assume the assay for the mutation will be done correctly in each case ...

This post originally appeared at Medical Lessons, written by Elaine Schattner, ACP Member, a nonpracticing hematologist and oncologist who teaches at Weill Cornell Medical College, where she is a Clinical Associate Professor of Medicine. She shares her ideas on education, ethics in medicine, health care news and culture. Her views on medicine are informed by her past experiences in caring for patients, as a researcher in cancer immunology and as a patient who's had breast cancer.