ARW's CGT+RNA Manufacturing Must-Reads (ARW IS ON A DEADLINE Edition!)

By Anna Rose Welch, Editorial & Community Director, Advancing RNA

Day-in and day-out, I write, read, listen to, and watch as much content as I can about CGT and RNA therapy manufacturing, in particular, and/or other ATMP industry-related topics that you should at least be aware of in the manufacturing facility. Every two weeks, I compile the articles and industry updates I think are most worthy of your time into an unconventional newsletter format (below) and send them out via email.

When this newsletter was sent out, I was on a deadline for a forthcoming Life Science Leader magazine article. So, in honor of my colleague who (nicely but quite directly) said he’d kill me if I miss said deadline, I introduced each section of these must-reads with a reference to some of our favorite “speedy” cartoon/comic book characters — just to keep things moving full speed ahead. God speed.

All of us have powers, skills, and abilities. Where I come from, heroes use those powers to...make the world a better place, whether it’s their world or not. ~ The Flash
[OUTSOURCING]

• My two favorite outsourcing “heroes” in the CGT industry — Adam Haskett (cell therapy) and Joe Graskemper (gene therapy) — are back! In part 2 of this three-part article series, they share how they’ve “used their powers, skills, and abilities” to evaluate the strengths and weaknesses of current CGT platform offerings at CDMOs.
• In addition to Adam’s and Joe’s perspectives, this article unpacking “how outsourcing doubled in the past 12 years” is well worth a read. Though BioPlan’s 20th Annual Report & Survey of Biopharmaceutical Capacity & Production report is predominantly biologics-focused, there were a few general outsourcing trends worth noting, including (but hardly limited to) the industry’s anticipated uptick in outsourcing analytical development and facility validation testing services.

Andale! Andale! Arriba! Arriba! Yii-ha! ~Speedy Gonzalez
[REGULATORY ADVANCEMENTS]

• Regulators are hardly the speediest mice in all the land. But they’re poised to make some big contributions to the CGT/RNA spaces in the months/years ahead.
• For starters, the FDA will be hosting an advisory committee meeting on October 31 for Vertex/CRISPR Therapeutics’ exa-cel, an ex vivo, CRISPR-edited gene therapy.
  • For a good write-up on exa-cel’s clinical results and safety concerns (as of June 2023), check out this article.
• Across the pond, the EMA is hard at work putting together guidelines to address the unique complexities of oligonucleotide development, manufacturing, and quality. This article provides a great breakdown of the anticipated scope of the guidelines, which are being crafted following industry commentary on a September 2022 concept paper.

Warning! The Tasmanian Devil is a powerful, vicious, evil-tempered brute — hungry at all times! It will eat anything but is especially fond of...
[CLINICAL HOLDS]

• Your clinical trial dreams. [Insert growling and slurping sounds here.]
• There are many intriguing data points in this recently published research digging into all (publicly announced) clinical holds for CGTs from January 2020-Dec. 2022. But most importantly, of the 33 holds, you’ll be intrigued to note that only 7 (or 21 percent) were directly caused by CMC issues (p. 7), which, on average, took roughly 8 months to resolve (p. 15).
• Likewise, it’s worth noting that data from Tufts has revealed that, despite their risks, CGTs for rare disorders or blood cancers are 2 to 3.5 times more likely to be approved than other therapeutic modalities.

I’m the top banana in a world full of hungry monkeys. ~Sonic the Hedgehog
[mRNA UPDATES]

• Intellia to Sonic: “Hold my peel.”
• We’ve been starving for late-stage clinical data demonstrating mRNA’s therapeutic (as opposed to prophylactic) potential, and now, thanks to Intellia, we’re on the verge of getting some. Intellia received FDA clearance to begin a Phase 3 trial of its in vivo (mRNA-based) CRISPR gene editing therapy.
• In 11 days, the mRNA industry will welcome its dedicated trade group, Alliance for mRNA Medicines. The Alliance previously held a “soft launch” at BIO in June and is poised to officially launch in Berlin at the mRNA Healthcare Conference.
• I’ve spent the past few weeks interviewing 4 executives for my forthcoming 2024 RNA Outlook article in Life Science Leader magazine. But to whet your appetite until its publication in December, you can digest some of the thoughts, predictions, and desires for the space from Omega Therapeutics, Eli Lilly, Arrowhead Pharmaceuticals, and Strand Therapeutics executives in my previously published 2023 Outlook article.
• If you require further sustenance, look no further than this hot-off-the-press article in which the authors compare Moderna and Pfizer’s respective vaccines, investigating how their ionizable lipids, untranslated regions, and nucleotide modifications impacted each vaccine’s delivery, protein expression, antibody generation, and stability.