In rare form

Posted by Ethan Perlstein in Research News on November 13, 2019 # Research

I’ve been thinking a lot lately about the parallels between rare genetic diseases and spinal cord injuries. Specifically, what can the SCI community learn from rare disease communities? There are at least five lessons worth learning.

First, embrace this n-of-1 moment – don’t shy away from it.
Every person living with SCI requires precision medicine, including personalized rehab. Each injury and its sequelae can be as unique as the pathophysiological cascade flowing from a single DNA mutation in the vast genome of an affected individual. If you sum all people living with SCI in the US, the total exceeds the 200,000 statutory threshold set by the Orphan Drug Act of 1983. Estimates are closer to 300,000 people living with SCI in the US today. However, none of the subgroups within SCI exceeds 200,000 when stratifying by the level of injury, which can be further sub-classified by time since injury, whether there is accompanying TBI (traumatic brain injury), and so forth.

Second, unlock the latent entrepreneurial potential and unique professional superpowers residing in the SCI community whether on the family/advocate side or on the researcher/clinician side.
While there is no equivalent of the rare genetic disease diagnostic odyssey in SCI, the challenges of embarking on the therapeutic odyssey are the same. As recently as a few years ago, highly motivated families, advocates, researchers and clinicians in the rare genetic diseases space could only dream of going from a diagnosis to a drug at record-breaking speed. Stories like this one out of Dr Tim Yu’s lab at Boston Children’s Hospital will become the new normal as small collaborative teams of scientists and advocates essentially create single-patient startups.

Third, avoid fragmentation and duplication of efforts at all costs.
It breaks my heart every time I see it. Even in the tiniest ultra-rare disease communities with global patient populations fewer than 50 people, I’ve seen feuds and rifts (almost always one-sided) over something as silly as whose child was the first to be diagnosed that prevent the community from rowing together as a team. I’ve seen one foundation organize and publish a natural history study only to have a second foundation working on the same exact disease launch a nearly identical natural history study but at a different clinical site and with a principal investigator that they controlled. The best remedy for fragmentation is to take an open, unrelenting, consensus-driven approach. (For a deeper dive, the history of the AIDS patient advocacy movement is instructive).

Fourth, make common cause with partners that put patients above maximizing profit and that care more about cures than credit or ego or power.
Foundations and their leadership have life cycles. Researchers have years of peak productivity within finite careers. Biotech companies launch and fail. Turnover is expected. Fresh blood free from legacy biases rejuvenates the community with regularity. Some foundations focus on research, some on caretaking, others still on advocacy and lobbying. That’s called a diverse ecosystem. The catch is to maintain a healthy, mutualistic ecosystem. It’s easier said than done but harmonize strategic planning and continually seek buy-in from the community; avoid psychopaths and narcissistic jerks no matter how rich or well-connected they are; and remember that licensing a program to BioPharma usually means giving up control over whether the program is funded all the way to the clinic or sold off well before when business priorities unexpectedly shift.

Finally, and most importantly, I believe the SCI community would benefit from adoption of the orphan regulatory mindset and framework, culminating in an effort to lobby Congress to create an Orphan Device Designation modeled after the Orphan Drug Designation.
The idea is to replace the outdated and ineffective Humanitarian Use Designation and Humanitarian Device Exemption programs, which currently lack any of the market incentives provided by the Orphan Drug Designation. Apparently the FDA head of devices agrees (alas, the article is paywalled). For example, ODD grants seven years of market exclusivity post-approval, FDA user fee waivers, and tax write-offs on R&D expenses. Why should the agency treat drugs and devices differently if they’re both intended for orphan indications? From a biological point of view, it shouldn’t matter whether the therapy is a small molecule drug, a biologic like an antibody, or a neuromodulatory device, especially if mechanistically speaking a drug and a device engage the same pharmacodynamic markers or evoke the same physiological adaptions post-intervention?

The Orphan Drug Designation pathway is a raging success if you go by the fact that nearly 40% of products approved by FDA last year were orphan drugs. Some have even said that the ODD has been too successful given the large number of (costly) specialty products approved over recent years. The SCI community would love to have this problem. I believe that creating an expanded ODDD, or Orphan Drug & Device Designation, would get the medical devices behemoths like Medtronic, GE, and Boston Scientific off the sidelines, and potentially incent non-medical devices companies to get into the space, too.