Rare disease insight: interview with Timothy Coté
Rebecca Aris interview Dr Timothy Coté
Cote Orphan Consulting
pharmaphorum’s Rebecca Aris interviews Dr Timothy Coté on the importance of the Orphan Drug Act and how large pharma companies can become more important forces in orphan drug development.
There are approximately 7,000 rare diseases, 200 of which have become treatable attributed, in no small part, to the Orphan Drug Act (ODA) of 1983. This act has helped to incentivise pharma into making progress in this field so much so that Orphan Drugs now represent about 40% of FDA drug approvals.
Former Director of FDA’s Office of Orphan Products Development, Dr Timothy Coté, is interviewed here on the importance of the ODA and how what pharma companies need to do in order to become more important forces in orphan drug development.
RA: Dr Coté, thank you for agreeing to take part in this interview, what’s inspired you into moving from the FDA into setting up your own consultancy?
TC: I was in the uniformed service, the US Public Health Service for 22 years and it was time to hang up the uniform. As you know, my last position brought me into this incredible community of people working on rare diseases – as Director of the FDA’s Office of Orphan Products Development (OOPD/FDA). I had the opportunity to work very closely with the review divisions in FDA, with patient advocacy groups and with companies large and small that want to enter the orphan drug space.
It was natural that from there I moved to two half-time positions, with the National Organization for Rare Diseases (NORD) in DC and another with the Keck Graduate Institute (KGI) in Claremont California where I teach regulatory affairs. The KGI position proved better suited to half-time employment, so while I still work a great deal with NORD (it’s a fantastic organization) I did resign my post as Chief Medical Officer.
Consulting, which has filled the gap, is turning out to be one of the most exciting jobs I have ever had in my life, looking from the outside in instead of from the inside out, I am able to chart clear paths for companies that are often stuck in some very confused places, and see them succeed not only financially, but in meeting some real medical needs.
“…the Office of Orphan Products Development is a promoter of drug development, not an impediment.”
RA: Looking back at your time at the FDA, what is the pivotal role of the office of orphan products development?
TC: The OOPD is the agency’s major advocate for creating new therapies for people with rare diseases. It has a unique role in this largely regulatory agency: the OOPD is a promoter of drug development, not an impediment. The staff I oversaw really came to work each day knowing that what they do makes a difference to the lives of everyday Americans, and their dedication to public service is extraordinary.
The Office’s role is to assure that patients with rare diseases don’t get “lost in the sauce” of drug development. Judging by the fact that Orphan Drugs now represent about 40% of everything the FDA approves, I’d say they have succeeded remarkably well.
RA: What incentives are in place to make orphan diseases a national priority in the US?
TC: The ODA of 1983 remains the statutory repository of most of the incentives, and orphan exclusivity continues to drive the system more than anything. Of course the ODA also has provisions for PDUFA fee exemptions and tax credits, but orphan exclusivity remains the most potent operant force.
PDUFA V has come forward with some new incentives – breakthrough exclusivity, vouchers for pediatric rare diseases, and others. In the context of my new consultancy, I am helping many companies to secure those incentives. But the ODA remains one of the best pieces of legislation ever passed for people with rare diseases, and it is functioning superbly.
“…the ODA remains one of the best pieces of legislation ever passed for people with rare diseases.”
RA: From a pharma perspective, how does the development process differ in orphan drug development compared with treatments for more common diseases?
TC: Orphans are special and different. The patient groups are your first big difference – developing an orphan drug requires a “high touch” effort that common diseases don’t need. When was the last time a statin maker courted the interest of a hypercholesterolemia patient advocacy group? Never. But try that with Pompe’s or Gaucher’s or Cystic Fibrosis or Friedreich’s Ataxia and you won’t have subjects for your clinical trials, advocates rooting for you at the advisory committees or customers to buy your drug if it ever does get approved.
Large pharmaceutical companies have much to learn before they can really become important forces in orphan drug development. They should join in and we definitely want them, but they have considerable unlearning to do (most won’t believe you can get a drug approved with a well-designed trial of 50 patients) and new learning to do (such as “high touch”). The good news is they no longer snivel at gross sales figures of merely $400M / year, so many of them are setting up places in their portfolios for orphan products. I’ll believe the results when I see them, and I’m here to help make those results a reality.
RA: How can a balance be struck between ensuring fair pricing of orphan drugs for pharma to account for increased development costs whilst ensuring patient access to treatments?
TC: Well, the basic principle of the ODA is that the exclusivity (of 7 years) is limited but the knowledge is eternal. What we need to see is more companies coming in at the end of those exclusivity periods and knocking down the price through good old competition, much as we saw for hand-held calculators 40 years ago. We have several instances in which this has happened, and the new biosimilars legislation goes a long way towards making that more accessible.
“Large pharmaceutical companies have much to learn before they can really become important forces in orphan drug development.”
RA: How do you strike a balance between ensuring the safety and efficacy of a rare disease drug with wanting to ensure that patients with rare diseases can access potentially the only available treatment option?
TC: The cruellest thing you could do to a person with a rare disease is to give them a “therapy” that doesn’t work while pretending it does. Put another way, as a matter of civil rights and social justice, patients with rare diseases are entitled to drugs that we know work, just as patients with common diseases are provided that assurance. And lastly, it has been the law of the land, since the 1962 amendment to the Food Drug and Cosmetics Act that all drugs, for rare and common diseases, need to demonstrate “substantial evidence of effectiveness” based on “well controlled trials”.
But you asked about balance. It is true that one cannot ask for the same 5,000 participant trial you might ask of a statin sponsor from the makers of a drug for some rare inborn error of metabolism. And this is where flexibility comes in. The Agency has consistently demonstrated the flexibility required to assure that patients with rare diseases are not locked out of the process of getting drugs for their illnesses simply because they’re rare. There have been clinical trails that have resulted in orphan drug approvals that have had 50, 30 some with even only 12 participants in them! Yet these trials still “meet the bar” in demonstrating “substantial evidence of effectiveness”. How can they do it? Through huge effect sizes — if your drug really works well you don’t need many subjects to show it. And as you know, many orphan drugs are therapeutic keys that fit snuggly into pathologic lock, turning patients lives completely around as they open new possibilities.
“The cruellest thing you could do to a person with a rare disease is to give them a “therapy” that doesn’t work while pretending it does.”
RA: How does National Organization for Rare Diseases collaborate with pharma and regulators to ensure patient access to treatment?
TC: NORD was the organization that brought us all the Orphan Drug Act and it continues to be the voice of the rare disease patient, in the community at large, with pharmaceutical companies and with legislators on the Hill. It is an extraordinary organization that started with the energy of parents at kitchen tables but has grown in professionalism and reach through the leadership of Peter Saltonstall and Abbey Meyer before him. NORD works to secure access through its relationships with FDA, industry and Congress, it can be expected to advance that leadership in the years to come.
RA: Dr Coté, thank you for your insights.
TC: It has been a pleasure and an honor to reflect on my engagement with this wonderful community. In my current roles as Professor at KGI and consultancy to a rapidly growing number of companies, I expect we are going to see a lot of miracles come to light.
About the interviewee:
Dr. Tim Coté is director of the FDA’s Office of Orphan Products Development. Coté’s office is responsible for implementing the 1983 Orphan Drug Act, originally the brainchild of a Connecticut woman whose children suffered from a rare disease. In the years since that Act was passed, says Coté, 357 new therapies have gone to full marketing approval and another 2,100 compounds that are “promising” have been labeled as orphan drugs. The Office of Orphan Product Development also serves as an ombudsman for everyone from patients groups to industry, expediting the development of drugs to fight approximately 7,000 rare diseases, including Gaucher’s, Pompe’s, Muscular Dystrophy, and Cystic Fibrosis – diseases that affect roughly 30 million Americans.
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