Pharmaceuticals Incorporated (Nasdaq: VRTX) today announced that it
received a Complete Response Letter from the U.S. Food and Drug
Administration (FDA) for its supplemental New Drug Application (sNDA)
for the use of KALYDECO® (ivacaftor) in people with cystic
fibrosis (CF) ages 2 and older who have one of 23 residual function
mutations in the cystic fibrosis transmembrane conductance regulator (CFTR)
gene. The FDA determined that it cannot approve the application in its
present form. Vertex plans to meet with the FDA to determine an
appropriate path forward.
“Our intention with this submission was to rapidly bring KALYDECO to
additional people with CF who we believe may benefit,” said Vertex
Executive Vice President and Chief Medical Officer, Jeffrey Chodakewitz,
M.D. “We chose to pursue this approach given our strong belief in the
science of CF and in the well-established safety of KALYDECO across many
different groups of people with CF. We are disappointed by this decision
and look forward to discussing with the FDA the next steps to bring
KALYDECO to people with CF who have these residual function mutations.”
The sNDA is based on preclinical data for ivacaftor in residual function
mutations, the established clinical profile of KALYDECO and on
previously reported data from an exploratory Phase 2a study. In 19 of
the 24 patients enrolled in this study, eight of the 23 mutations
proposed in the sNDA were represented.
CF is caused by defective or missing cystic fibrosis transmembrane
conductance regulator (CFTR) proteins resulting from mutations in the CFTR gene.
The defective or missing proteins result in poor flow of salt (chloride)
and water into and out of the cell in a number of organs, including the
lungs. Chloride transport is a marker of the function of the CFTR
protein at the cell surface. KALYDECO, which received the FDA’s
Breakthrough Therapy Designation in 2013, is currently approved in the
U.S. to treat people with CF ages 2 and older who have one of 10
mutations in the CFTR gene (G551D, G1244E, G1349D,
G178R, G551S, S1251N, S1255P, S549N, S549R
or R117H). As with the mutations for which KALYDECO is approved,
this group of 23 residual function mutations is known to have some
functional CFTR protein at the cell surface. This submission was also
based on observed in vitro increases in chloride transport in
response to ivacaftor in cells expressing CFTR. The presence of CFTR
protein at the cell surface and increases in chloride transport are
characteristics associated with clinical response to KALYDECO.
There are more than 1,500 people ages two and older with CF in the
United States who have one of the 23 residual function mutations
included in the sNDA. The 23 residual function mutations included in the
sNDA are: 2789+5G->A, 3849+10kbC->T, 3272-26A->G, 711+3A->G, E56K,
P67L, R74W, D110E, D110H, R117C, L206W, R347H, R352Q, A455E, D579G,
E831X, S945L, S977F, F1052V, R1070W, F1074L, D1152H, and D1270N.
KALYDECO® (ivacaftor) INDICATION AND
IMPORTANT SAFETY INFORMATION
KALYDECO (ivacaftor) is a prescription medicine used for the treatment
of cystic fibrosis (CF) in patients age 2 years and older who have one
of the following mutations in their CF gene: G551D, G1244E, G1349D,
G178R, G551S, S1251N, S1255P, S549N, S549R, or R117H.
KALYDECO is not for use in people with CF due to other mutations in the
CF gene. KALYDECO is not effective in patients with CF with two copies
of the F508del mutation (F508del/F508del) in the CF gene.
It is not known if KALYDECO is safe and effective in children under 2
years of age.
IMPORTANT SAFETY INFORMATION
Patients should not take KALYDECO if they are taking certain medicines
or herbal supplements such as: the antibiotics rifampin or
rifabutin; seizure medications such as phenobarbital, carbamazepine or
phenytoin; or St. John’s wort.
Before taking KALYDECO, patients should tell their doctor if they have
liver or kidney problems; drink grapefruit juice or eat grapefruit or
Seville oranges; are pregnant or plan to become pregnant because it is
not known if KALYDECO will harm an unborn baby; and are breastfeeding or
planning to breastfeed because is not known if KALYDECO passes into
KALYDECO may affect the way other medicines work, and other medicines
may affect how KALYDECO works. Therefore the dose of KALYDECO may need
to be adjusted when taken with certain medications. A patient should
especially tell their doctor if they take antifungal medications such as
ketoconazole, itraconazole, posaconazole, voriconazole, or fluconazole;
or antibiotics such as telithromycin, clarithromycin, or erythromycin.
KALYDECO can cause dizziness in some people who take it. Patients should
not drive a car, use machinery, or do anything that needs them to be
alert until they know how KALYDECO affects them. Patients should avoid
food containing grapefruit or Seville oranges while taking KALYDECO.
KALYDECO can cause serious side effects. High liver enzymes in the blood
have been reported in patients receiving KALYDECO. The patient’s doctor
will do blood tests to check their liver before starting KALYDECO, every
3 months during the first year of taking KALYDECO, and every year while
taking KALYDECO. For patients who have had high liver enzymes in the
past, the doctor may do blood tests to check the liver more often.
Patients should call their doctor right away if they have any of the
following symptoms of liver problems: pain or discomfort in the upper
right stomach (abdominal) area; yellowing of their skin or the white
part of their eyes; loss of appetite; nausea or vomiting; or dark,
Abnormality of the eye lens (cataract) has been noted in some children
and adolescents receiving KALYDECO. The patient’s doctor should perform
eye examinations prior to and during treatment with KALYDECO to look for
cataracts. The most common side effects include headache; upper
respiratory tract infection (common cold), which includes sore throat,
nasal or sinus congestion, and runny nose; stomach (abdominal) pain;
diarrhea; rash; nausea; and dizziness.
Please click here
to see the full Prescribing Information for KALYDECO (ivacaftor).
About KALYDECO® (ivacaftor)
KALYDECO (ivacaftor) is the first medicine to treat the underlying cause
of CF in people with specific mutations in the cystic fibrosis
transmembrane conductance regulator (CFTR) gene. Known as a CFTR
potentiator, KALYDECO is an oral medicine designed to keep CFTR proteins
at the cell surface open longer to improve the transport of salt and
water across the cell membrane, which helps hydrate and clear mucus from
KALYDECO is approved in the U.S., Europe, Canada, Australia and New
Zealand to treat people with CF who have specific genetic mutations in
the CFTR gene.
Vertex retains worldwide rights to develop and commercialize KALYDECO.
About Cystic Fibrosis
Cystic fibrosis is a rare, life-threatening genetic disease affecting
approximately 75,000 people in North America, Europe and Australia.
CF is caused by a defective or missing CFTR protein resulting from
mutations in the CFTR gene. Children must inherit two
defective CFTR genes — one from each parent — to have
CF. There are approximately 2,000 known mutations in the CFTR gene.
Some of these mutations, which can be determined by a genetic test, lead
to CF by creating defective or too few CFTR proteins at the cell
surface. The defective or missing CFTR protein results in poor flow of
salt and water into or 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 in
many patients that eventually leads to death. The median predicted age
of survival for a person born today with CF is 41 years, but the median
age of death is 27 years.
Collaborative History with Cystic Fibrosis Foundation Therapeutics,
Vertex initiated its CF research program in 1998 as part of a
collaboration with CFFT, the nonprofit drug discovery and development
affiliate of the Cystic Fibrosis Foundation. KALYDECO and ORKAMBI®
(lumacaftor/ivacaftor) were discovered by Vertex as part of this
Vertex is a global biotechnology company that aims to discover, develop
and commercialize innovative medicines so people with serious diseases
can lead better lives. In addition to our clinical development programs
focused on cystic fibrosis, Vertex has more than a dozen ongoing
research programs aimed at other serious and life-threatening diseases.
Founded in 1989 in Cambridge, Mass., Vertex today has research and
development sites and commercial offices in the United
States, Europe, Canada and Australia. For six years in a row, Science magazine
has named Vertex one of its Top Employers in the life sciences. For
additional information and the latest updates from the company, please
Special Note Regarding Forward-looking Statements
This press release contains forward-looking statements as defined in the
Private Securities Litigation Reform Act of 1995, including, without
limitation, Dr. Chodakewitz's statements in the second paragraph of the
press release and Vertex’s plans with respect to a potential meeting
with the FDA. While Vertex believes the forward-looking statements
contained in this press release are accurate, there are a number of
factors that could cause actual events or results to differ materially
from those indicated by such forward-looking statements. Those risks and
uncertainties include, among other things, that Vertex may not be able
to obtain approval for KALYDECO as a treatment for people with CF who
have residual function mutations, that data from the company's
development programs may not support registration or further development
of its compounds due to safety, efficacy or other reasons, and the other
risks listed under Risk Factors in Vertex's annual report and quarterly
reports filed with the Securities and Exchange Commission and available
through the company's website at www.vrtx.com.
Vertex disclaims any obligation to update the information contained in
this press release as new information becomes available.
View source version on businesswire.com: http://www.businesswire.com/news/home/20160205005336/en/