One of the most important keys to successful relationships – be it in life or rare disease drug development – is open, honest and frequent communication, according to a panel of rare disease experts speaking at the Therapeutic Workshop: “Balancing the Rick-Reward in Rare Disease Drug Development” at the BIO CEO & Investor Conference in New York on Monday. Without engaging the key groups at the right time and the right manner, companies entering this space will be adding significant risk to their business, they said.
As Big Pharma has struggled to replace revenues lost after the patents expired on many of their blockbuster pills popped daily by millions, many healthcare investors have turned their focus to companies looking to treat severe, debilitating diseases that affect 30 million Americans a year.
On the surface, panelists said, regulatory pathways for these so called “orphan drugs” seem smoother, clinical trials are smaller and overall cheaper, market exclusivity is locked in for seven years and, with a tiny population of target patients – who are often well organized and have few or no other options – the commercial plan seems to almost write itself. But it’s not that simple.
“One of the great myths is that the FDA will give you a pass,” said Timothy Coté, M.D., MPH, Principal and CEO of Coté Orphan Consulting, a Washington, D.C. based consulting firm that assists biotech and pharmaceutical companies through regulatory hurdles in the US and EU and specializes in helping clients obtain orphan status designation for their therapeutics. “That is very much a myth…all drugs have to have substantial proof of effectiveness.”
Around 80 percent of rare diseases are genetic, most affect children and many of them are extremely debilitating and even deadly. Regulators do want good products to get to these patients – and will work with companies dedicated to that same goal. But it’s up to the companies to push for the collaboration.
“It’s better to get to the regulators right away. The golden rule is, ‘Meet with them early and meet with them often,’” Dr. Coté advised. “One of the biggest mistakes companies make is waiting until they have all their ducks in a row.”
He advises companies to push for meetings to discuss endpoints and trial design as soon as they’re eligible for Orphan Drug Designation, have as many meetings as possible prior to filing an investigational new drug application (IND) and apply for Breakthrough Therapy Designation (for drugs demonstrating potential for substantial improvement over existing therapies), regardless of whether they think they will get it. The breakthrough status application filing alone will mean another conversation and touch point with the agency, he said. Actually receiving breakthrough designation, however, will mean many, many more.
One of the major issues – and reasons to collaborate early with the FDA on clinical trial design and the development of meaningful outcome measures – is that these are usually first-in-class compounds and diseases where no one really understands how they naturally progress, according to panelist Seng H. Cheng, Ph.D., Head of Research & Early Development in Genzyme’s Rare Diseases Division.
That’s been particularly true for companies like Prosensa, a pioneer in the quest to find a treatment for Duchenne Muscular Dystrophy (DMD), a rare and severely debilitating childhood neuromuscular disease that leads to progressive loss of muscle function. Boys with DMD are often wheelchair bound before the age of 12 and few survive past age 30.
Over the last five years as over 300 boys with have been enrolled in its clinical and natural history studies, Prosensa has garnered substantial insights into what is clinically meaningful for patients and regulators. Together, they have decided that a test to measure how far the boys can walk in six minutes is a solid quantitative measurement, however, there are qualitative nuances to consider, Hans Schikan, CEO of Prosensa explained.
“What about boys who cannot walk [when they enter the study] or those who are too young to listen to a physiotherapist saying ‘Keep walking’?” Schikan asked. “Duchenne boys are looking for practical outcomes, like, ‘Can I walk from the car to my school.’”
Building strong relationships with the families affected by rare diseases can help shed light on the nuances and practical endpoints that matter on a personal level.
“We get letters from parents all over the world, and it is a huge privilege, but there is a burden on the company to do the right thing. We have to ensure we have balanced communications and not over-promise,” said Mr. Schikan. “Whenever we put out a press release, we try to think of how a parent will read every sentence. When we speak to patients, the risk/reward comes out very quickly.”
Understanding what the patients and their families are going through, also is a constant reminder of why companies are in the business of rare diseases.
Allison M. Parks is a healthcare communications consultant with Lazar Partners LTD.