Market Overview

FDA Approves ORKAMBI® (lumacaftor/ivacaftor) as First Medicine to Treat the Underlying Cause of Cystic Fibrosis for Children Ages 2-5 Years with Most Common Form of the Disease


- Approximately 1,300 people in the U.S. ages 2 through 5 years have
two copies of the F508del mutation, the most common genetic form of the
disease -

Pharmaceuticals Incorporated
(NASDAQ:VRTX) today announced the U.S.
Food and Drug Administration (FDA) has approved ORKAMBI® (lumacaftor/ivacaftor)
to include use in children ages 2 through 5 years with cystic fibrosis
(CF) who have two copies of the F508del-CFTR mutation, making it
the first medicine approved to treat the underlying cause of CF in this
population. ORKAMBI oral granules are available in two dosage strengths
(lumacaftor 100mg/ivacaftor 125mg and lumacaftor 150mg/ivacaftor 188mg)
for weight-based dosing. ORKAMBI oral granules should be available for
fulfillment within 2 to 4 weeks.

"For the first time, children ages 2 through 5 who have the most common
form of CF have a treatment for the underlying cause of their disease,"
said Reshma Kewalramani, M.D., Executive Vice President and Chief
Medical Officer at Vertex. "We believe it is important to treat the
underlying cause of the disease as early as possible and this approval
is another significant milestone in our journey to bring effective
medicines to all people living with CF."

This FDA approval is based on a Phase 3 open-label safety study in 60
patients that showed treatment with ORKAMBI was generally safe and well
tolerated for 24 weeks, with a safety profile similar to that in
patients ages 6 years and older. Improvements in sweat chloride, a
secondary endpoint, were observed at week 24 (mean decrease in sweat
chloride from baseline of 31.7 mmol/L; 95% CI: -35.7, -27.6, n=49).
Researchers also saw changes in key growth parameters, which were also
secondary endpoints in the study. The most common adverse event (≥30%)
was cough (63%); most adverse events were mild or moderate in severity.
Four patients experienced serious adverse events (2 pulmonary
exacerbations, 1 gastroenteritis, 1 constipation) and three patients
discontinued treatment due to treatment emergent adverse events or
elevated liver function tests. These findings were presented at the 41st
European Cystic Fibrosis Society Conference in June 2018.

"Cystic fibrosis is a systemic, multi-organ, progressive disease that is
present from birth," said Dr. John McNamara, Medical Director of the
cystic fibrosis program at Children's Minnesota hospital and lead study
researcher. "Research suggests ORKAMBI could impact CF outcomes in
patients as young as two years old. This approval is a significant
development that enables physicians to begin treating the underlying
cause of the disease in this population earlier than ever before."

ORKAMBI was already approved in the U.S. for the treatment of CF in
patients ages 6 and older who have two copies of the F508del-CFTR
mutation. A Marketing Authorization Application (MAA) line extension for
ORKAMBI in children ages 2 through 5 years has been submitted to the
European Medicines Agency (EMA) with a decision anticipated in the first
half of 2019.

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 cystic fibrosis transmembrane
conductance regulator (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, or genotyping test, lead to CF by creating
non-working or too few CFTR proteins at the cell surface. The defective
function or absence of CFTR protein results in poor flow of salt and
water into and out of the cell in a number of organs. In 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 age of death is in the
mid-to-late 20s.

About ORKAMBI (lumacaftor/ivacaftor)

ORKAMBI is a combination of lumacaftor, which is designed to increase
the amount of mature protein at the cell surface by targeting the
processing and trafficking defect of the F508del CFTR protein,
and ivacaftor, which is designed to enhance the function of the CFTR
protein once it reaches the cell surface.


ORKAMBI is a prescription medicine used
for the treatment of cystic fibrosis (CF) in patients age 2 years and
older who have two copies of the F508del mutation (F508del/F508del)
in their CFTR gene. ORKAMBI should only be used in these
patients. It is not known if ORKAMBI is safe and effective in children
under 2 years of age.

Patients should not take ORKAMBI if they are taking certain medicines
or herbal supplements, such as:
the antibiotics rifampin or
rifabutin; the seizure medicines phenobarbital, carbamazepine, or
phenytoin; the sedatives and anti-anxiety medicines triazolam or
midazolam; the immunosuppressant medicines cyclosporine, everolimus,
sirolimus, or tacrolimus; or St. John's wort.

Before taking ORKAMBI, patients should tell their doctor about all
their medical conditions, including if they:
have or have had liver
problems; have kidney problems; have had an organ transplant; or are
using birth control. Hormonal contraceptives, including oral,
injectable, transdermal, or implantable forms should not be used as a
method of birth control when taking ORKAMBI. Patients should tell their
doctor if they are pregnant or plan to become pregnant (it is unknown if
ORKAMBI will harm the unborn baby) or if they are breastfeeding or
planning to breastfeed (it is unknown if ORKAMBI passes into breast

ORKAMBI may affect the way other medicines work and other medicines
may affect how ORKAMBI works.
Therefore, the dose of ORKAMBI or
other medicines may need to be adjusted when taken together. Patients
should especially tell their doctor if they take: antifungal medicines
such as ketoconazole, itraconazole, posaconazole, or voriconazole; or
antibiotics such as telithromycin, clarithromycin, or erythromycin.

When taking ORKAMBI, patients should tell their doctor if they stop
ORKAMBI for more than 1 week
as the doctor may need to change the
dose of ORKAMBI or other medicines the patient is taking.

ORKAMBI can cause serious side effects, including:

Worsening of liver function in people with severe liver disease.
The worsening of liver function can be serious or cause death. Patients
should talk to their doctor if they have been told they have liver
disease as their doctor may need to adjust the dose of ORKAMBI.

High liver enzymes in the blood, which can be a sign of liver
injury. The patient's doctor will do blood tests to check their
liver before they start ORKAMBI, every three months during the first
year of taking ORKAMBI, and annually thereafter. The patient should call
the 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 the skin or the white part of the eyes;
loss of appetite; nausea or vomiting; dark, amber-colored urine; or

Breathing problems such as shortness of breath or chest tightness
in patients when starting ORKAMBI, especially in patients who have poor
lung function. If a patient has poor lung function, their doctor may
monitor them more closely when starting ORKAMBI.

An increase in blood pressure in some people receiving ORKAMBI.
The patient's doctor should monitor their blood pressure during
treatment with ORKAMBI.

Abnormality of the eye lens (cataract) in some children and
adolescents receiving ORKAMBI. For children and adolescents, the
patient's doctor should perform eye examinations before and during
treatment with ORKAMBI to look for cataracts.

The most common side effects of ORKAMBI include: breathing
problems, such as shortness of breath and chest tightness; nausea;
diarrhea; fatigue; increase in a certain blood enzyme called creatinine
phosphokinase; rash; gas; common cold, including sore throat, stuffy or
runny nose; flu or flu-like symptoms; and irregular, missed, or abnormal
periods (menses) and increase in the amount of menstrual bleeding.

Side effects seen in children are similar to those seen in adults
and adolescents. Additional common side effects seen in children
include: cough with sputum, stuffy nose, headache, stomach pain, and
increase in sputum.

Please click here
to see the full Prescribing Information for ORKAMBI.

About Vertex

Vertex is a global biotechnology company that invests in scientific
innovation to create transformative medicines for people with serious
and life-threatening diseases. In addition to clinical development
programs in CF, Vertex has more than a dozen ongoing research programs
focused on the underlying mechanisms of other serious diseases.

Founded in 1989 in Cambridge, Mass., Vertex's headquarters is now
located in Boston's Innovation District. Today, the company has research
and development sites and commercial offices in the United States,
Europe, Canada and Australia. Vertex is consistently recognized as one
of the industry's top places to work, including being named to Science
magazine's Top Employers in the life sciences ranking for eight years in
a row.

For additional information and the latest updates from the company,
please visit

Collaborative History with Cystic Fibrosis Foundation Therapeutics,
Inc. (CFFT)

Vertex initiated its CF research program in 2000 as part of a
collaboration with CFFT, the nonprofit drug discovery and development
affiliate of the Cystic Fibrosis Foundation. KALYDECO®
(ivacaftor), ORKAMBI®(lumacaftor/ivacaftor), SYMDEKO®
(tezacaftor/ivacaftor and ivacaftor), VX-659 and VX-445 were discovered
by Vertex as part of this collaboration.

Special Note Regarding Forward-looking Statements

This press release contains forward-looking statements, as defined in
the Private Securities Litigation Reform Act of 1995, as amended,
including the statements by Dr. Kewalramani in the second paragraph and
Dr. McNamara in the fourth paragraph of this press release and
statements regarding (i) the timing of shipping of the oral granules in
the United States and (ii) the anticipated timing of an EMA decision on
the MAA line extension. While the company 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
regulatory authorities may not approve, or approve on a timely basis,
the company's drug candidates 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 Vertex's website at
Vertex disclaims any obligation to update the information contained in
this press release as new information becomes available.


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