Phase 2 Study of Kalydeco and VX-661 in Combination Shows Promising Results

Vertex Pharmaceuticals Inc. today announced promising results from a Phase 2 clinical trial of its cystic fibrosis drug Kalydeco™ in combination with another potential CF therapy, VX-661.

Both Kalydeco and VX-661 are designed to treat the underlying cause of CF, a faulty gene and its protein product, known as CFTR.
“Today’s announcement is more terrific news for the CF community,” said Robert J. Beall, Ph.D., president and CEO of the Cystic Fibrosis Foundation. “These results show that another potential therapy from our ongoing collaboration with Vertex can be paired with Kalydeco and achieve promising improvements in health. The data further validate our strategy of using small molecule compounds to address the basic genetic defect in cystic fibrosis.”

The results showed a significant improvement in lung function in people with two copies of the most common CF mutation, Delta F508, who took the combination treatment, compared with those who received a placebo.

About 50 percent of people with CF in the United States have two copies of the Delta F508 mutation.

The Phase 2 study enrolled 128 people ages 18 and older with two copies of the Delta F508 mutation of CF. Four different doses of VX-661 were evaluated in combination with Kalydeco. Those who received the two highest doses of VX-661 showed the greatest improvement in lung function.

VX-661 is the second potential therapy that Vertex has studied in combination with Kalydeco in people with two copies of the Delta F508 mutation. Vertex is also studying Kalydeco with VX-809 in two Phase 3 trials that will enroll about 1,000 people at approximately 200 clinical trial sites in North America, Europe and Australia.

Vertex plans to conduct additional studies of VX-661 and Kalydeco in combination, pending discussions with regulatory agencies.
In today’s announcement, Vertex also said it plans to begin a Phase 1 study later this year to evaluate Kalydeco in combination with the potential CF drug VX-983 in people with two copies of the Delta F508 mutation.

The CF Foundation played a key role in the development of Kalydeco, VX-809, VX-661 and VX-983, providing significant scientific, clinical and financial support. The U.S. Food and Drug Administration approved Kalydeco in January 2012 for people with the G551D mutation of CF.

"The CF Foundation is deeply grateful to the people with CF, families and medical professionals who have played a role in these studies, and to the Vertex scientists who remain dedicated to advancing CF drug development," said Beall.

Previous Announcements

FDA approves Novartis TOBI® Podhaler™

FDA approves Novartis TOBI® Podhaler™ for certain cystic fibrosis patients, the first and only dry powder inhaled antibacterial in US

East Hanover, NJ, March 22, 2013 –Novartis announced today that the US Food and Drug Administration (FDA) has approved TOBI® Podhaler™ (tobramycin inhalation powder) 28 mg per capsule for the management of cystic fibrosis (CF) patients with Pseudomonas aeruginosa (Pa) bacteria in the lungs. Pa is the leading cause of loss of lung function in CF patients. It is not known if TOBI Podhaler is safe and effective in patients under six years of age, in those with lung function outside of a certain range, or in those whose lungs contain bacteria called Burkholderia cepacia.

TOBI Podhaler is a new, non-nebulized formulation and delivery system of tobramycin, the same active ingredient as in TOBI® (tobramycin inhalation solution, USP)

300 mg/5 mL, which has been on the market for approximately 15 years. TOBI Podhaler is the first and only FDA-approved dry powder inhaled antibacterial for Pa in the US. It delivers tobramycin into the patient’s lungs via a pocket-sized dry powder inhaler and offers better portability than TOBI, which is administered using a nebulizer. In a Phase III study, TOBI Podhaler shortened administration time for patients by approximately 70% compared to TOBI, saving about 13 hours per treatment cycle. This does not include the time saved on setting up and maintaining the nebulizer and compressor.

TOBI Podhaler does not need to be stored in a refrigerator and, unlike nebulized Pa treatments, does not require a power source to operate the delivery device. While the nebulizer used to administer TOBI must be disinfected in boiling water for 10 minutes every other treatment day, the disposable Podhaler device must only be wiped clean with a dry cloth after each use and is then replaced weekly.

“This is good news for the CF community,” said Robert J. Beall, Ph.D., President and CEO, Cystic Fibrosis Foundation. “Managing daily CF treatments is a challenge for people with CF.  TOBI Podhaler helps relieve that burden by shortening the time it takes to administer the medicine and making it easy for people with CF to take their treatment with them wherever they need to go.”

The new TOBI Podhaler dry powder formulation was developed using proprietary Novartis PulmoSphere™ technology. This technology enables the creation of hollow porous particles of tobramycin that can be delivered as a dry powder rather than as a nebulized solution.

“TOBI Podhaler is an example of how Novartis is utilizing innovative technologies to better meet the needs of patients. By eliminating the need for a nebulizer to deliver tobramycin and providing a small, lightweight design, TOBI Podhaler reduces administration time and improves portability for patients on-the-go,” said André Wyss, President of Novartis Pharmaceuticals Corporation. “It also underscores our long-term commitment to the cystic fibrosis community."

TOBI Podhaler was studied in a Phase III clinical program involving 674 CF patients aged six years and older with Pa in their lungs, of whom 425 patients received at least one dose of TOBI Podhaler. Two trials evaluated the efficacy of TOBI Podhaler vs. placebo, while a third trial assessed the safety of TOBI Podhaler vs. TOBI. All studies evaluated TOBI Podhaler at the approved dose of 112 mg twice daily (the contents of four 28 mg capsules per dose) in cycles of 28 days on, immediately followed by 28 days off treatment. Results of the efficacy studies showed that TOBI Podhaler improved lung function compared to placebo.

The safety of TOBI Podhaler was evaluated in 425 patients who received at least one dose of TOBI Podhaler, including 273 who were exposed across three cycles. In the two placebo-controlled efficacy trials, adverse reactions reported more commonly with TOBI Podhaler compared to placebo included pharyngolaryngeal pain (sore throat), dysphonia (voice alteration) and dysgeusia (taste disturbance) in one study and cough and hypoacusis (decreased hearing) in the other study. In the safety study, the most commonly reported adverse reactions (as defined as >10% in either treatment arm) with TOBI Podhaler were cough, lung disorder (pulmonary or CF exacerbations), productive cough, dyspnea (shortness of breath), pyrexia (fever), oropharyngeal pain (sore throat), dysphonia (voice alteration), hemoptysis (coughing up blood) and headache.

New Infection Prevention and Control Policy

The Cystic Fibrosis Foundation recently implemented a new infection prevention and control policy for all Foundation events, meetings and offices to protect the health of people with CF. They took this step based on increasing medical evidence that the risk of people with CF spreading destructive germs to one another is greater than was previously thought. The new policy reflects the advice of leading medical experts on this subject.

The health and well-being of people with CF is the topmost concern. The CF Foundation has had infection control guidelines in place to promote the safety of people with CF. With this new policy, the CF Foundation is acting proactively and immediately to reduce the risk of cross-infection among people with CF. 

The key elements of the Foundation’s new policy are:

  • At any CF Foundation-sponsored indoor event or meeting, including gatherings like committee meetings, only one person with CF may be present and he or she will be designated in close consultation with event chairs and key event volunteers.
  • At Foundation-sponsored outdoor events or gatherings, people with CF need to maintain a distance of at least 6 feet from each other.
  • Under no circumstances shall individuals who have ever had a confirmed positive sputum culture for Burkholderia cepacia (B. cepacia) complex attend any CF Foundation events, meetings or offices. 

The CF Foundation understands that these changes are disheartening and difficult for many in the community. Among the many burdens of CF is that of social isolation. The Foundation also recognizes the unique challenges that the new policy poses to adults with CF, whose full engagement is vital to helping better serve the entire CF community. The Foundation embraces and owes so much of its success to the active participation of people with CF in all activities, from major fundraising and advocacy campaigns to informal meetings in chapter offices.

Fortunately, there are alternative ways that can make Foundation events more accessible to people with CF. The Foundation is expanding the use of teleconferencing and live videocasts so people can take part in group activities remotely. The Foundation is also exploring other new technologies to help engage people with CF more creatively and draw on their talents and experiences to strengthen collective efforts.

You can find more information about the new policy, including FAQs, in a new section on the Foundation’s website:

CF Foundation Finalizes Pharmacy Alliance with Walgreens

The Cystic Fibrosis Foundation and Walgreens announced today that they have formally launched an alliance that gives the national drugstore chain a significant ownership stake in CF Services Inc., the Foundation’s specialty pharmacy.

The Foundation remains a partial owner of CF Services. The pharmacy will remain based in Bethesda, Md., and will continue to use its current name.

Walgreens and CF Services will work together to ensure as seamless a transition as possible for customers. CF Services customers will continue to use the same toll-free number to order medications and will interact with the same knowledgeable professionals. Customer-friendly services, such as free shipping and monthly invoices for out-of-pocket payments, will continue.

In the longer term, CF Services expects to provide new services and benefits to customers and their families.

The CF Foundation entered the alliance to provide the CF community with greater access to affordable medications and expanded pharmacy services, and to enable the Foundation to expand our patient assistance programs. Increasingly, our patient access and support programs and advocacy efforts are an important lifeline to the CF community. The alliance allows the CF Foundation to fortify these programs significantly.