Advancing Research Progress: A Conversation with Dr. Beall
Robert J. Beall, Ph.D., president and
CEO of the Cystic Fibrosis Foundation
Nearly 15 years ago, the Cystic Fibrosis Foundation embarked on a journey to support the development of oral therapies targeting the underlying cause of CF.
At the time it was not known whether it would be possible to treat the defective CFTR protein and improve key symptoms of the disease.
Since its approval in early 2012, the oral drug Kalydeco™ has shown that it is. For the hundreds of people around the world with the G551D mutation who are now taking the drug, it has been life-changing.
Even more exciting for the entire CF community are the new opportunities that the medical success of this drug has created.
Vertex Pharmaceuticals Inc., the maker of Kalydeco, has started two large, international Phase 3 trials testing Kalydeco in combination with the potential drug VX-809 in people with two copies of the most common CF mutation, Delta F508.
These studies, which have enrolled about 1,000 people, are potentially the most significant in the history of the disease. If they are successful, close to half of those living with CF could benefit from new cutting-edge treatments.
Several years ago, the Foundation launched its “second-generation” effort to ensure that additional potential drugs were advancing in development in case Kalydeco and VX-809 did not gain U.S. Food and Drug Administration (FDA) approval and to seize any opportunity to improve upon the effectiveness of these first generation therapies.
The goal of all of these new and expanded drug discovery and development efforts is to treat the underlying cause of CF in all people with the disease, and — to put it in the words of Robert J. Beall, Ph.D., president and CEO of the Foundation — “Leave no mutation behind.”
Shortly before the 2013 North American Cystic Fibrosis Conference, Connections spoke with Beall about the latest progress in CF drug development and steps the Foundation is taking to advance the search for a cure.
What new drug development opportunities is the CF Foundation supporting?
While we are excited about the progress made to target the basic defect, we have always been an organization that has thought ahead and are already building on that progress.
The wonderful thing about our second-generation initiative is that, through our venture philanthropy program, we have been able to attract other major pharmaceutical companies to the CF effort in addition to Vertex, such as Pfizer and Genzyme. So far, we have committed more than $150 million to this effort and the prospects look very promising.
We are also continuing to invest in all aspects of the disease, and we are continuing to examine new approaches to develop new antibiotics and anti-inflammatories.
It is gratifying to have such an array of partners in the fight against CF. Our momentum has never been greater.
Can the CF community expect to see any new drugs approved soon?
We are very encouraged by the results from the Vertex Phase 2 trial of Kalydeco and VX-809. These results satisfied the requirements of both the FDA and Vertex to move ahead with a Phase 3 clinical trial.
But we know that treating the Delta F508 mutation is especially challenging. This mutation creates several problems that prevent the CFTR protein from functioning properly. Fixing these problems will likely require two drugs or more.
The reality of the drug discovery and development process is there is always a risk of failure and disappointment. This happened several years ago with the potential CF drug denufosol, which had advanced to a Phase 3 trial but was not developed further.
With all Phase 3 trials, we must bear in mind that the ultimate goals are safety and efficacy and meeting FDA requirements for approval. We will look forward to results of the Phase 3 trial of Kaldyeco and VX-809 in late 2014 or early 2015.
What about people with rare mutations who might benefit from Kalydeco or other new therapies?
Currently, Kalydeco has only been approved for 4 percent of the CF population, but late-stage trials are moving forward that could help bring the drug to more people. It is expected that close to 15 percent of people with CF could benefit from Kalydeco as a single therapy; we will know more later this year.
But even if the drugs that are in clinical trials now become available to greater numbers of people, they will not work for all CF mutations. We’re going to need new approaches to reach the rest of the CF population.
We are encouraged by the progress made toward treating people with one copy of the Delta F508 mutation. As we speak, Vertex is studying combinations of other potential drugs with Kalydeco to examine which compounds and doses would be best to move forward in clinical trials.
The Foundation is pushing ahead with an aggressive program to treat people who have what are known as nonsense mutations as well as those with other rare mutations — approximately 10 percent of the CF population. It’s possible that some of these mutations could respond to different small molecule approaches, and we’re exploring that with several collaborators.
We also are in discussions with other companies that have cutting-edge technologies that could potentially help us address the underlying cause of CF regardless of a person’s mutation. Remember, our goal is to reach 100 percent of all CF mutations. Our goal is: No mutations left behind.
What role do royalties play in the Foundation’s strategy?
One component of our venture philanthropy model is that, when a drug is approved, the Foundation receives a royalty payment from the sale of the drug. This payment allows us to continue to aggressively invest in our CF drug pipeline.
For instance, our royalties from the antibiotic TOBI® helped fund our first Vertex collaboration. We are already using the royalties from Kalydeco to help fund new CF research projects with other companies. It would have been virtually impossible for the Foundation to make the sizable commitments to the CF programs of Pfizer, Genzyme and others were it not for the funds derived from our royalty agreements.
We have also expanded funding to advance drug discovery and support our ongoing efforts to keep our entire pipeline stocked with new treatments that tackle the disease from every angle. New antibiotic approaches are central to that effort.
What challenges have come with these successes?
We are very concerned — and have voiced our concerns with the pharmaceutical companies whose research we fund — about the rising cost of all CF drugs, which can place such a heavy burden on people with CF and their families. These costs are also unsustainable for the country’s health care system overall.
It is essential that we find ways to balance innovative research with the need for affordable treatments. The Foundation is actively encouraging and participating in a national dialogue on this issue. We are calling for collaboration among advocacy groups, the research community, the pharmaceutical industry and health insurers to create solutions that help advance new life-saving treatments while ensuring that they are accessible to those who need them.
What is the CF Foundation doing to help people get the treatments they need?
We advocate strenuously on behalf of people with CF and their families to help them get the treatments they need, and have recently expanded our patient access and advocacy programs.
Our Patient Assistance Resource Center connects people with CF and their families to an array of free resources to help them decide on health care coverage that’s right for them, make the most of that coverage and find programs to help them pay for their CF treatments.
We also offer a free CF Legal Information Hotline, where people can get answers to questions that can be very challenging to solve on one’s own, such as eligibility requirements for Medicaid and Medicare. Last year alone the Hotline addressed more than 5,200 calls.
Our public policy program — assisted by thousands of volunteer advocates across the country — works with lawmakers in all 50 states and the U.S. Congress to raise awareness of CF and build support for improving access to specialty drugs and to quality CF care.
Anything else you would like to share about what lies ahead?
In my 30-plus years at the Foundation, I have personally never been as excited as I am now about what the future holds for our community.
We have a terrific care center network and a clinical trials network that is second to none.
We have created a culture of research that has attracted companies that bring powerful capabilities to our cause. And with partners like Vertex, Pfizer, Genzyme and others focused on developing new treatments for CF, we have strong cause to be optimistic about our future.
Yes, we should always be prepared for some possible disappointments. But I am confident that with the tremendous momentum we have gained, and the passion and dedication that has long defined the CF community, we can also expect more success in the near future.
I recently spoke at a Foundation event where I noticed a young woman sitting in the front row crying. I continued on and hoped the rest of my speech would help calm her fears. Later, the woman — who I learned is a CF mom — shared with me what had moved her to tears. Her child is on Kalydeco and her health has improved dramatically. Her daughter, she said, has never been better.
This young mother was crying tears of hope and joy, not tears of despair and fear.
I want all parents and people with CF to have that experience.
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