What Baby KJ Taught Us About Sustainable mRNA Development
By Anna Rose Welch, Editorial & Community Director, Advancing RNA
As I shared in my previous article, I had the opportunity to attend a new conference a few weeks back. This one-day inaugural (soon to be annual) event called Building RNA Medicine Excellence was put on by the Alliance for mRNA Medicines and Franklin Biolabs in Philadelphia. Not only am I a sucker for a one-day event, but I was also struck by how nicely each of the talks complimented the event’s purpose: To discuss building the infrastructure to treat many more Baby KJ’s.
Much like the pandemic approval of the COVID vaccines, the dosing of Baby KJ was a heroic milestone worth celebrating. And to be clear, there’s a lot we can learn from extraordinary situations, especially as we strive to build our regulatory and public policy frameworks from the ground up for mRNA. But what we haven’t necessarily done yet is step back and parse through what made the Baby KJ situation possible and which of those factors is/are feasibly replicable.
There was one panel discussion during this event that I wish could be replicated on conference stages the world over. It was a conversation that took place between JHU’s Jeff Coller, CHOP’s Rebecca Ahrens-Nicklas, and Plowshare Therapies’ Kevin Strauss. This was exactly the conversation the space needed to have because it started to answer a critical question: What did the Baby KJ experience teach us?
Of course, these conversations are rarely simple, and the learnings are multifaceted. In the following three-part series, I’ll share my 3 biggest takeaways from the discussion between Coller, Ahrens-Nicklas, and Strauss. As you’ll no doubt see, their experiences working closely with patients in the rare disease community give us a grounded look at the Baby KJ experience and drug development for rare disease that help build a realistic framework from which we can work moving forward.
Here in part 1, I’ll start by parsing out the learnings about drug development we can take away from the overall heroic efforts to dose Baby KJ. Part 2 will provide a glimpse into what we’ve learned about personalized therapy COGS, and Part 3 will tackle patient/physician communication strategies.
Why Expanded Access Isn’t A Long-Term Model
All of us in this industry know that good science and manufacturing both don’t happen overnight. In fact, one of the biggest reminders to the public (and to ourselves) following the COVID pandemic was that mRNA wasn’t exactly “new.” We’d been working on it for 20-plus years. In the same way, the Baby KJ experience was far from a last-minute decision. As Ahrens-Nicklas reaffirmed for everyone, being able to treat KJ in such a heroic manner required a foundation and partners who were ready to move earth and sky to make it happen.
“This experience taught me that if you have a story and a cause, people will collaborate and push something forward,” Ahrens-Nicklas said. “But this was built on years and years of work. It wasn’t like KJ was born and we suddenly decided, ‘Hey, we’re going to do this.’ We had been collaborating for four years to develop a way to produce these editing therapies quickly.”
As she went on to acknowledge, the production of Baby KJ’s therapy was still a “huge sprint,” despite the years of preparation. But there were numerous instances in which the stars did align to make this a somewhat unusual and “lucky” case. For one, there was a CDMO with NHPs available to carry out the tox studies “at the drop of a hat.” There were manufacturing slots available, and, even more importantly, the manufacturing run was successful.
“This experience taught us that it’s possible,” Ahrens-Nicklas added. “But it also taught us that this model is not sustainable, and we need to come up with more sustainable methods and models to develop individualized therapies.”
Of course, for the physicians at CHOP, this experience instilled knowledge around gathering preclinical data, clinical trial design, and off-target editing analysis. But this was also a therapy that was offered under an expanded access IND — a choice that Ahrens-Nicklas cautions shouldn’t become a tactic we rely extensively on moving forward. Though she emphasized that it was an important strategy to show what is possible in drug development for ultra-rare diseases, it isn’t a catch-all solution. Not only would carrying out a series of single-patient expanded access INDs be resource intensive and very quickly diminish grant funding, but it also doesn’t necessarily pave the way toward an official approval the way an official clinical trial does.
“The fastest way to get the potential benefits of this type of drug is to open a formal clinical trial,” she added. “If we do a series of single patient expanded access INDs, we wouldn’t have generated the knowledge that’s necessary to support an approval, and we really need approvals in this country given our insurance system to be able to pay for them.”
Of course, as you can imagine, this experience has led to thousands of requests from patients’ families about the prospect of individualized development — many of which we cannot yet treat until we solve our delivery limitations. But for patients with urea cycle disorder, Ahrens-Nicklas has continued to emphasize the importance of establishing a clinical trial for future approval. This has required level-setting with patients.
“You say, ‘Listen, we want to make sure that we are doing this the right way, so we know what we need to do to move this forward for a community, not just an individual,’ she clarified. ‘And I will tell you, families understand that. So, a lot of what we’ve been doing since this story broke has been putting our heads down, raising the money, and doing the work that needs to be done to generate the data to eventually progress toward approvals.”
Stay tuned for learning number 2!