Rare Diseases: Abandon Everything You Think You Know

by Susan Nemetz, November 2018

Rare Diseases: Abandon Everything You Think You Know

By Marnie Hoolahan

“Overcoming the hurdles has built a great faith in me that things can be done to help people with rare diseases. It will drive my optimism forever and my belief in achieving things that seem impossible.”

—Henri Termeer, CEO of Genzyme,
who launched the first lifesaving treatment, Ceredase, for Gaucher Disease

I am and will always be an admirer of Henri Termeer, former CEO of Genzyme. Although we mourned his passing in 2017, during his more than 25 years leading the company, he set an example for all of us who worked at Genzyme and in the industry at large, regarding how our work in life sciences can positively impact the lives of others.

It’s in the area of rare diseases, though, that he left his greatest and longest lasting impression on me and my view of the work we do.

They’re Called “Rare” for a Reason

Let’s begin with some data.

A rare disease (or “orphan disease” as the regulatory agencies call them) is one which affects fewer than 200,000 patients in the US or is, “fatal or severely debilitates 5 per 10,000 inhabitants in the EU.” There are many diseases — more than 7,000 — affecting a total of 25-30 million people in the US alone, half of whom are children.

That’s nearly one in ten Americans. And yet, despite this relatively large number (it’s about the same as the percentage of people who are left-handed), rare disease treatments are exceedingly hard to develop and bring to market. The investment in time and resources, as well as the approach required, is quite different than what many of us are used to with more well-known illnesses.

Can a company be successful in rare disease? Yes, absolutely. Genzyme’s success with Ceredase/Cerezyme for Gaucher Disease is just one example. Thanks to the passage of the Orphan Drug Act in 1983 and, more recently, the Orphan Drug Modernization Plan, there are federally granted benefits that make rare disease development more commercially attractive to life science companies that invest in this area.

The sheer volume of companies venturing down the orphan disease path is significant. Since 1983, the FDA has granted more than 650 orphan drug approvals, nearly 4,500 orphan drug designations, and has received more than 6,300 orphan drug designation requests. In 2017, the FDA received orphan drug designation requests at a rate of 1.4 per day and granted designation requests at a record rate of 1.3 per day! (Source: fdalawblog.net)

That said, the people inside those companies recognize that developing a drug in a rare disease takes a very different approach, culture, and mindset. Specific challenges that are unique to rare diseases (especially rare diseases without an acute mortality association)include:

It’s hard to find patients.

You can’t run a clinical trial without patients, of course, but finding those who characterize a rare disease is neither easy nor obvious. Most patients don’t even know they have a disease, let alone which one it is. For them, it may just look like a collection of unrelated and persistent symptoms, none of which seem to fall under any classification or relate to anyone else’s condition.

Indeed, given the fact that the average rare disease patient consults with five doctors, receives three misdiagnoses, and waits four years before receiving a final diagnosis, it’s easy to see how difficult this can be on patients and their caregivers.

It’s hard to find doctors.

Physicians are used to dealing with un-exceptional ailments. When a patient arrives with a set of symptoms, it’s understandable that the doctor looks for what’s most common. Even if there is an underlying genetic component, we don’t screen people for every conceivable possibility (and even if we did, new diseases are not yet in any medical textbook).

In most cases, it’s not until several specialists — often through informal networks and communications — are able to sense a pattern, put the relevant pieces together, and recognize the symptoms for what they are, that a diagnosis emerges.

It’s hard to know where to start.

Well-known diseases and some established rare diseases are represented by foundations and patient groups. They hold fundraising events. They are covered in the press. Most important, the science is advanced, and there may already be therapies available.

The unfamiliar, nascent or newly identified rare diseases are the polar opposite; in terms of information, there is no centralized anything.

In addition to the patient and physician limitations, the science is novel, the medical advances are slow, and advocacy doesn’t yet exist (it’s no wonder that the parents of children with rare diseases are so often the ones who launch foundations and advocacy organizations).

A Cross-Functional Group Effort

When it comes to making progress with rare diseases, the process is necessarily nonformulaic. Typically, we begin by asking lots of questions and identifying what we know. Are there publications? Is there epidemiology or natural history? Is there a genetic component? Has NORD identified it?

From there, we will conduct secondary research via scientific publications (NORD reference links, PubMed, Google Scholar), orphan designation searches on FDA and EMA sites, indication searches at The Human Side of Our Work

The people who are afflicted with rare diseases and their families are not part of a large population. Often, they feel abandoned, isolated, and scared. When you meet or hear from them firsthand, there is a much more intimate connection, and you become invested. Your mission is to support theirs: you become the advocate for them, not necessarily the disease with which they are labeled.

The truth is, part of what makes work in rare diseases so frustrating is also what makes it so rewarding. It’s a constant reminder of the human side — and the collaboration required — in the work we do.

Conclusion

Had I never been exposed to Genzyme and Henri, I would not be as committed as I am to rare disease. He had a way of persuading all of us of our obligation to save lives and let the success of the company follow from the passion for patients.

This recent quote from John, a patient with a rare disease, is a constant reminder of the value of our work and the impact we can have:

“I cannot describe how amazing our lives will change if we can have a near-normal immune system simply by taking a pill. To that end, we will be delighted to do whatever we can to help in your success. We are at your disposal.”

Marnie Hoolahan and Henri Termeer

Marnie Hoolahan and Henri Termeer