Cambridge, Massachusetts-based Vertex Pharmaceuticals Incorporated announced Monday that it has signed a letter of intent with the pan-Canadian Pricing Alliance (pCPA) to enable public reimbursement of Kalydeco (ivacaftor) drug therapy for treatment of eligible Canadians ages 6 and older with cystic fibrosis (CF) who have the G551D gene mutation. The letter of intent represents an agreement in principle with the pCPA regarding public reimbursement of Kalydeco in Canada.
However, before patients can get access through public reimbursement, because public medical care is constitutionally a provincial or territorial responsibility, each participating province or territory must decide to reimburse Kalydeco through its individual drug program. Kalydeco is the first medicine to treat the underlying cause of cystic fibrosis for people with the G551D mutation in the CFTR gene. In Canada, there are approximately 100 people ages 6 and older with this specific mutation.
Cystic fibrosis is a life-threatening genetic disease affecting approximately 75,000 people in North America, Europe and Australia. People with CF have a poor flow of salt and water into and out of the cells of a number of organs, including the lungs. This results in a buildup of abnormally thick, sticky mucus that can cause chronic lung infections and progressive lung damage. Today, the median predicted age of survival for a person with CF is between 34 and 47 years, but the median age of death globally remains in the mid-20s (32 in Canada). CF is caused by a defective or missing CFTR protein, the result of a mutation in the CFTR gene. Only children who have the misfortune to inherit two faulty CFTR genes — one from each parent — have the disease, affecting roughly one in every 3,600 children born according to Cystic Fibrosis Canada, and there are more than 1,900 known mutations in the CFTR gene. Some of these mutations, which can be determined by a genetic, or genotyping test, lead to CF by creating non-working or too few CFTR proteins at the cell surface. Kalydeco only works for a small subset of CF patients — those whose disease is caused by a particular mutation on the CFTR gene called G551D. There are several other mutations for which the drug is useful and is licensed, but people with those mutations make up a tiny fraction of Canadian CF cases.
Kalydeco, an oral medicine that aims to help the CFTR protein function more normally once it reaches the cell surface, to help hydrate and clear mucus from the airways thus facilitating increased chloride transport by potentiating the channel-open probability (or gating) of the CFTR protein, was discovered as part of a collaboration with Cystic Fibrosis Foundation Therapeutics, Inc. (CFFT), the nonprofit drug discovery and development affiliate of the Cystic Fibrosis Foundation. Vertex initiated its CF research program in 1998 as part of a collaboration with CFFT, and this collaboration was expanded to support the accelerated discovery and development of Vertex’s CFTR modulators.
Kalydeco was granted U.S. Food and Drug Administration approval in January 2012 in approximately three months — one of the agency’s fastest FDA approvals ever. Kalydeco (150mg, q12h) was first approved by the for use in people with CF ages 6 and older who have at least one copy of the G551D mutation and in February 2014 for use in people with CF ages 6 and older who have the following additional CFTR mutations: G178R, S549N, S549R, G551S, G1244E, S1251N, S1255P and G1349D. In Canada, KALYDECO was first approved in November 2012 for use in people with CF ages 6 and older who have at least one copy of the G551D mutation and in June 2014 for use in people with CF ages 6 and older who have the following additional CFTR mutations: G178R, S549N, S549R, G551S, G1244E, S1251N, S1255P, G1349D and G970R. KALYDECO was approved by the European Medicines Agency in July 2012 and by the Therapeutic Goods Administration in Australia in July 2013 for use in people with CF ages 6 and older who have at least one copy of the G551D mutation in the CFTR gene.
Rapid approvals notwithstanding, a challenge for patients is that Kalydeco is exceedingly expensive. The Website Cancer Treatment Meds cites Kalydeco’s price according to Vertex Pharmaceuticals, at $512.06 per pill. Annual cost of the medication is roughly CAN$350,000 in Canada.
The main reason for this high cost is because Kalydeco is exclusively indicated to treat only a relatively small sub-minority of what is an already relatively small number of cystic fibrosis cases overall who have at least one copy of the G551D mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. The CF prevalence rate in general in the most vulnerable ethnic group, caucasians, being just one in every 2,500 births. Consequently, since the proportion of cystic fibrosis cases positive for the G551D mutation in the CFTR gene is very low, with only few CF patients eligible to use Kalydeco. The bottom line, literally, is that because it is indicated only for treatment of an exclusive and small group of patients, economies of scale associated with sales of more widely-prescribed drugs don’t obtain with Kalydeco, keeping the cost per patient high.
“The letter of intent signed today with the pan-Canadian Pricing Alliance is an important step toward eligible Canadians receiving Kalydeco through public reimbursement. However, our work is not complete until each province has added Kalydeco to its individual drug program to ensure people can get access to this medicine,” said Stuart Arbuckle, Executive Vice President and Chief Commercial Officer for Vertex in a release. “We share the urgency of the CF community to bring this process to a successful conclusion, and we will work as quickly as the provinces are able to so that people can receive Kalydeco without delay.”
The process to add Kalydeco to Canadian public drug programs at the provincial and territorial level is ongoing. The letter of intent does not include the province of Quebec, which does not participate in the pCPA process. Vertex employs approximately 75 people across Canada and has established Commercial and Medical teams in Canada to support the use of Kalydeco.
Kalydeco is now available to eligible people with CF in more than 15 countries around the world, including the United States, England, Scotland, Northern Ireland, Wales, the Republic of Ireland, France, Germany, the Netherlands, Austria, Denmark, Sweden, Norway, Greece, Italy and Switzerland. Kalydeco was approved in Australia in July 2013, however public reimbursement discussions are ongoing.
Another potential avenue for eligible patients financially excluded from treatment is enrollment clinical trials, which the National Institutes of Health (NIH) defines as research studies that test how well new medical approaches work in people. An expanded access program for Kalydeco is currently open at participating clinical trial sites in the United States. This program is designed to provide Kalydeco to people ages 6 and older who have at least one copy of the G551D mutation, are in critical medical need and may benefit from treatment prior to potential FDA approval in the United States.
You can find out more about clinical trials in your area by using the CF Foundation’s clinical trial search tool. This tool has recently been updated to allow you to search for clinical trials in cystic fibrosis using three methods:
For more information, visit:
The Cystic Fibrosis Foundation
Vertex Pharmaceuticals Incorporated
National Institutes of Health
Cancer Treatment Meds