Rare Disease Day is Every Day For Many…

While Rare Disease Day is marked each year on February 28, our journey since my son’s diagnosis with a rare disease makes it our everyday reality – but it doesn’t have to be. New therapeutic innovations are on the horizon, but we need to ensure the regulatory and policy choices are ready for them, or innovative new medicines could stall in development.

I have been on a lifelong journey to develop new medicines that make “leaps and bounds” differences for patients. Prior to joining Alltrna, my 20-year career in the industry has been in pharma bringing to patients new innovations in oncology, from targeted therapies to immuno-oncology. A new course for me was set nearly three years ago, when my son, Caffrey, was diagnosed with Duchenne muscular dystrophy (DMD), an X-linked, genetic, progressive, muscle-wasting disease affecting about 1 in 3,500–5,000 live male births. There is no known cure, and it is 100% fatal. With that diagnosis, we became members of the rare disease community.

I did what many of us parents in the community do to understand his disease and researched the investigational cutting-edge innovations that might alter his natural outcome, leveraging my experience in drug development. Although it was reassuring to learn that progress in DMD is being made, even with some advanced therapies in late-stage development, I was shocked to discover that Caffrey was eligible for exactly zero of these clinical trials. It seemed like there was nothing we could do but wait and, as with others suffering from progressive conditions, we are in a literal race against time.

Being thrust into the rare disease space really opened my eyes to the huge unmet need in this community that is not being served by conventional drug discovery and development. Programs overlook massive numbers of patients and are painstakingly slow, tackling one disease or gene at a time. As I worked to understand more about genetically driven diseases such as Duchenne, I found myself wondering how we can harness biology and direct it toward correcting these ill-fated errors and, critically, how we can do so at a much faster pace.

Being thrust into the rare disease space really opened my eyes to the huge unmet need in this community that is not being served by conventional drug discovery and development.

Today, we tackle genetically driven diseases using very conventional approaches, focusing on each disease and gene individually. But with over 6,000 known genetically driven diseases affecting more than 300 million people around the world, it is clear how truly insurmountable this challenge is when addressed in this fashion. This is one of the major reasons why there has been so little innovation in the last decades, with only 5% of rare genetic diseases having an FDA-approved medicine, no matter its safety and/or benefit profile.

Caffrey is at least one of the lucky few with a diagnosis that gets some attention, but the reality is that most people with genetically driven diseases will get none. And, similar to what we heard when Caffrey’s horrifying diagnosis was delivered, millions of these families will be told to go home and spend time with their loved ones because there is nothing that can be done.

Each of these 300M+ people living with a genetic condition deserves better. And we, the collective healthcare field, must find transformational approaches to address this massive unmet need. Quickly.

One such approach is being advanced by Alltrna, and it’s a major reason why I decided to join this company as CEO. Alltrna has established a transfer RNA (tRNA) platform to correct disease at the genetic source. tRNAs play a central role in the translation of mRNA into proteins. However, the instructions are not always perfect and mutations in the mRNA can lead to a premature stop, causing disease. This type of mutation – called a premature termination codon (PTC) – affects about 10 percent of all patients living with genetically driven conditions. With this tRNA platform, we can design new therapeutics to not just correct PTCs in one disease, but in many diseases, providing an alternative to the painstakingly slow gene-by-gene strategy utilized today.

With this tRNA platform, we can design new therapeutics to not just correct PTCs in one disease, but in many diseases, providing an alternative to the painstakingly slow gene-by-gene strategy utilized today.

While private sector innovation like Alltrna’s will be critical for rare disease patients, we also cannot ignore the role that inspired public policy plays in creating the environment in which such innovation can flourish. Take, for example, the recent passage by Congress of bipartisan legislation directing the Food & Drug Administration to develop a new program to expedite the development and review of medicines that are created using the same technological platform – like Alltrna’s tRNA platform. If implemented wisely by the FDA, such an approach could transform the speed at which new genetically targeted medicines can reach rare disease patients in need, without compromising safety or quality. Now that the ball is in FDA’s proverbial court, Congress and other interested stakeholders must remain vigilant to ensure the full benefit of this approach can be realized.

On the flip side, poor policy choices – like the recently enacted Medicare drug price controls – can seriously undermine the incentives to invest in diseases that only impact a few people per disease. While Congress properly exempted rare disease drugs from such government price controls, it eliminated this exemption if a company sought to apply its medicine to more than one rare disease. This approach is exactly the wrong approach if we want to incentivize more treatments for more rare diseases. Indeed, at least one company has already publicly announced the cancellation of a drug development program for an important rare disease because of this provision. While Congress likely did not intend such a result, it must act quickly to fix this flaw in the law before more companies are forced to abandon rare disease treatments out of fear of government price controls.

Recently, I attended the celebration of life in memory of the passing of a young man with DMD — he was the first individual I knew personally that died with this disease. Unfortunately, he won’t be my last. Every single day, patients with genetic diseases are dying. They don’t have the luxury of waiting. So, for me, now is not the time to wait or to hope. It’s time to act to ensure our policy decisions are aligned with new therapeutic innovations. For those 300M+ people with genetic diseases, for Caffrey, for me, it’s personal.

By

Michelle Werner

Michelle Werner joined Flagship Pioneering in 2022 as CEO Partner and CEO of Alltrna. Michelle brings more than two decades of pharmaceutical leadership spanning both Commercial and Research and Development responsibilities. She most recently…