Getting orphan drugs approved and to the patient is what drives Tim Coté, CEO of Coté Orphan

By Erin Righetti

Dr. Tim Coté is a no-nonsense guy. The principal and chief executive officer of Coté Orphan is as passionate about orphan drug filings as he is pragmatic. Ask him about lofty theoretical viewpoints on curing disease and you might get a short answer. But ask him about how to get your orphan drug designation application through the FDA to approval and you will unleash the inspiration behind his boutique full-service regulatory group laser focused on orphan drugs, Coté Orphan.

Tell me about Coté Orphan and your objective.

I was the former Director of the FDA’s Office of Orphan Products Development (OOPD), and in that capacity signed off 1,400 orphan drug indications, awarding designations to 800 and withholding approval of 600. I saw 150 orphan drugs go all the way to market approval. I started this consultancy four to five years ago at my kitchen table. Someone asked if I could write one a regulatory filing and then the floodgates opened. Now we have 25 employees, many with PhDs, and we do work here and in Europe. Business is booming for orphans, business is hot.

Is the drug development industry by nature becoming a rare disease market?

I believe so. I told Dr. Margaret “Peggy” Hamburg, the former FDA chief, that we were taking over. That comment was prescient. Most FDA approvals are for orphans; orphans are tightly connected to the science that is evolving. Orphans are most of what a doctor learns in medical school, about rare disease and how the body functions.

Most of us have a urea cycle; there are all kinds of different ways that the urea cycle can go sideways. That’s what it is about rare disease, they are fundamental to biological diseases. Rare disease is more tightly targeted to dysfunctional biology.

More common diseases, such as diabetes, cardiovascular disease, etc,, these are complex multifactorial conundrums. But take sickle cell disease, the gene defect is a known mutation of a single nucleotide with known immune system pathways. We can trace those pathways; they are simpler and easier for our brains to understand.

What are the biggest challenges in developing drugs for orphan indications?

It’s limited only by our imagination. The biggest challenges in developing orphan drugs right now are finding patients, running clinical trials, which are expensive, and getting good regulatory input. I see the entire drug development process through a regulatory lens. Our challenge is in overturning an old world view of theoretical effectiveness to focusing on the need for evidence of safety and effectiveness.

We just saw success with an indication for orotic aciduria—a trial involving just four people resulted in an approved drug because we demonstrated safely and effectiveness as substantial evidence. It’s not about the number of people in a trial but the safety and effectiveness.

The biggest challenge is understanding that regulatory affairs for orphan drugs is different from regulatory affairs you would need for drugs that treat a common disease. The reason it’s different is because the agency (FDA) affords special flexibility in filing for an orphan indication.

Is it easier to get a “breakthrough” designation from the FDA if you have a rare disease drug?

The FDA would say no. Breakthrough therapy design is open to orphan and non-orphan, the statutes do not limit them to orphan indications. Orphans are overrepresented. Having said that, my company assists other companies in securing regulatory approvals, and we help with orphan designation. A large number of filings that go through my office result in ner orphan drug designations.

We do everything but only for orphan drugs.

You are sponsoring a breakfast at the upcoming BioPharm America™ event in Boston. Why do you value involvement in BioPharm America?

We value our involvement with BioPharm America because the person-to-person meetings are valuable opportunities to really understand where the is client coming from. Here’s what we do: we increase success for our clients and we make our clients rich, we increase their asset value by securing sound regulatory decisions. The day after the drug gets orphan designation, it vastly increases in value and so gets an incredible return on investment. That is a solid reason to get regulatory advice; we write the submissions.

We actually produce deliverables so our client companies can submit to the FDA. We don’t just opine. We do the work of creating quality regulatory filings. I see the world through a regulatory lens. Ideas themselves aren’t worth spit. In order to sell anything you have to get through to the people at the FDA. You have to answer, what does it mean to them? You have to demonstrate that this drug has advanced safety and effectiveness.

What the FDA cares about is, can the sponsor demonstrate that they make the sick person well? How do you demonstrate that? You don’t do that with a molecule in the lab, you do that with people, by curing sick people. We go to clients and try to translate their good work into something the FDA can understand. Only then is the product worth something. The FDA has the monopoly on drug approvals.

What kinds of partnerships are you looking to forge at BioPharm America?

We work for 300 clients, and we will see a lot of them at BioPharm America. We are looking for new people with exciting ideas. People who want to bring their products into commercial value. We are very practical. We are looking for people who want to increase their asset’s value. Very rarely will a company discover, develop and distribute a drug. There are many partners involved at every level. We increase the asset’s value so that when you are ready for the asset to change hands, it’s worth more.

If I am thinking about a rare disease development strategy, what would you put on the strategy checklist?

Regulatory affairs, regulatory affairs, regulatory affairs. It’s just like real estate. That’s the only thing that’s going to get it on the market.

Companies come to us and say, “We’ve talked to all these scientists.” I don’t care. I care what the people at [the FDA’s] White Oak [campus] think. You may have brainy people at universities who think this is the best approach, but they are somewhat irrelevant compared to the people in White Oak who are concerned with making the sick well. I strongly recommend companies begin their approach this way. Too many companies start with their regulatory affairs too late. These academic institutions are invaluable but they are not a go-to. For commerce we need to convince the dispassionate everyman, our trusted public servants, that this product is safe and effective and it won’t happen exclusively through a discussion of molecular mechanisms. That is not how a drug gets to market.

What motivates you?

What motivates me personally? We’re kicking butt for some real important problems. Today I was speaking to someone about malaria vaccines. If it gets through it has the potential to affect millions of people. In contrast, I was talking to someone whose son has Duchenne muscular dystrophy. They have a really decent chance of developing a product that that will save this child’s life. These are powerful stories and they are exciting. I’m just a government scientist, and now, I am apparently in business. What motivates me? You could say I very much enjoy flying an airplane while I’m building it.

Meet Dr. Coté at BioPharm America global life science partnering taking place September 13–15 in Boston.