A knock on a door one evening in 2011 changed the focus of Henri Termeer, former CEO of Genzyme. Soon, perhaps, it will change the lives of many other people. Daniel de Boer, a 29-year-old engineer, knocked without knowing Termeer. A friend had arranged the introduction. de Boer’s young son had been diagnosed with cystic fibrosis, and de Boer was determined to find a way to help him and the many other patients with this disease. Today, a therapy developed by the company he formed, ProQR, is about to enter clinical trials.
That story is important, Termeer told the crowd at Biotech Showcase™ 2017, because it shows how important patient advocacy is in bringing rare disease research to the clinic and, eventually, to patients. “Almost no rare disease work occurs in a company without patients somehow being connected to its start,” Termer, now a board member of Aura Biosciences, says. Since that meeting, he has been involved in developing therapeutics for more than 15 rare diseases.
Patient advocacy is another outcome. When Debra Miller’s son was diagnosed with Duchenne muscular dystrophy in 2002, she invested EUR 1 million in a tiny Dutch biotech company that was developing a treatment. When the company was acquired by BioMarin, Miller used her proceeds to invest in four more biotechs and one academic research project. Somewhere during the process, she co-founded and became the CEO of CureDuchenne. Explaining that decision, she says, “The more patients share knowledge, the earlier we can take that knowledge to companies to invest in these drugs. There’s also a lot the FDA doesn’t know about rare diseases.”
Rare diseases demand a different mindset
“We know very little about most rare diseases,” Termeer says. The industry generally doesn’t understand what it means to live with most of these diseases, or to care for those who have them. Patients, their families and patient foundations, therefore, are invaluable in helping drug developers understand the day-to-day realities of rare conditions. “Without that connection with patients, there is no chance of going after the approximately 7,000 rare diseases (of which only 400 have therapies).”
Phil Vickers, head of R&D and member of the executive committee of Shire, agrees. “The paradigm for development in the rare disease space is completely different (than for common conditions). Often, no one has developed a drug for that disease. How can they if they don’t understand the disease?” Involving patients and patient foundations is critical, both to learn their experiences and “to understand the value we can bring to a disease area.”
At Shire, Vickers says, “Patients speak at each senior leadership meeting, to ground what we do. But to actually prioritize the work, companies need people who can embrace uncertainty.” In rare diseases a broad body of research often is lacking, so key opinion leaders and regulators are engaged extraordinarily early. Companies also must discuss holistic costs with payers, discussing not just the potential price of a therapy, but the healthcare costs of not developing a therapy or of living with inaccurate diagnoses.
Shire’s rare disease programs focus on areas of high unmet needs that often have no effective standard of care. But, Vickers adds, “Programs must be clinically doable. We are a business, and our shareholders expect innovation and growth. Therefore, we concentrate on areas where we are uniquely focused to drive advancements and translate patient needs into a concrete pipeline.”
Innovating to move the needle
“Innovation isn’t just a new drug target or technology,” Vickers says. It can be a business development model, too. “We’re very flexible about how to move programs forward.” Sometimes that means providing encouragement or specific goals for companies before making an initial investment. The company also provides seed funding, working with venture capitalists to identify promising companies before their clinical results become public. Sometimes, Shire gives companies access to some models. “Anything to move the program forward is fair game,” Vickers says.
Each year the infrastructure to support rare disease drug development improves. Regulatory bodies, for instance are starting to embrace changes to support rare disease drug development. They are beginning to recognize some of the limitations and to understand that classical endpoints aren’t always possible. “The FDA is becoming aware of the needs of very small patient population trials and is very focused on getting things done,” Temeer says.
When a company decides to work in rare diseases, it can’t walk away. “These are deep commitments. They are not casual,” he continues. “You can’t disengage easily as long as you have a shot. Sometimes you start a program and a patient benefits, and you know that for the rest of that patient’s life, you must support him. You are the lifeline for that patient,” Termeer emphasizes.
As Vickers concurs, “We recognize we bring tremendous hope to a community that had nowhere to turn, and we take it seriously. This puts you in unusual situations.”
Compassionate use requests are a good example. “A well-controlled trial involves patients whom you believe can benefit, but what happens to patients outside those strictures? In pediatrics, how can you run a placebo-controlled arm of a study for a disease that has a high mortality rate? You have to have conversations like this with regulators very early,” Vickers says.
Miller, as a patient advocate and mother, reiterates the profound commitment and deep emotional involvement of the biotech companies she has worked with in the Duchenne space. The industry has worked with CureDuchenne to sponsor roadshows to train physical therapists far from major treatment centers how to treat boys with Duchenne. “It wouldn’t have been possible without their sponsorship,” she says.
At a personal level, taking on these rare diseases has been very different from tackling the common diseases of our time, Vickers says. “I can’t imagine another job with so much satisfaction. We change lives and give people hope. It’s rejuvenating.”
Or, as Termeer adds, “No activity can compete with working in a space where you can change the outcome for patients and their families.”
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Editor-in-Chief, InsightFollow on Twitter More Content by Erin Righetti