San Diego, CA—The annual Cell & Gene Meeting on the Mesa in San Diego kicked off this week with a packed schedule of sessions and some 40 company presentations that speak to the significant progress in these burgeoning therapeutic fields.

Organized by the Alliance for Regenerative Medicine, the program has attracted more than 1,700 attendees, 20% of whom are C-level executives. Although opting for a hybrid format, the enthusiastic number of live attendees signaled the thrill and benefits of live conferences and networking.

Commercialization is around the bend

The opening plenary session covered current trends and challenges surrounding gene therapy commercialization. Moderated by Dave Lennon, PhD, CEO of Satellite Bio, the panel discussed critical topics related to bringing these potentially life-changing treatments to market: pricing, the hurdles of early access, accelerated approval requirements, novel go-to-market challenges, and considerations of global equity.

Arguably the key rate-limiting step for commercialization is regulatory approval. Debbie Drane, senior vice president (SVP) of Global Commercial Development and Therapeutic Area (TA) Strategy at CSL Behring, discussed how regulators do not understand all diseases equally. Some of the targeted rare diseases do not have a clinical or regulatory precedent. Regardless of a regulatory body’s familiarity with a disease, Drane thinks making durability claims with gene editing can be tricky. For example, CSL Behring’s EtranaDez, potentially the first gene therapy for patients living with hemophilia B, accepted by the FDA for priority review last May, will have to be compared to existing chronic treatments.

Regarding access to gene therapy before approval, Matthew Klein, MD, chief operating officer (COO) at PTC Therapeutics, said, “We’re in a special situation with one-time administered gene therapies. That’s different than when you have a repeat-administered small molecule, for example, where you can leverage compassionate use programs and expanded access programs to accelerate commercialization on the other side of approval. Obviously, with a one-time administrative therapy, you must think carefully about how that plays out.”

Klein laid out PTC’s different approaches, including early access programs to leverage treating patients before finalizing pricing and negotiation. “We’re looking to European countries like France with early access programs that allow us to provide commercial drugs prior to finalizing reimbursement discussions,” he said.

Upon drug approval, one of the first things that happen is that patients and families worldwide start to reach out. According to Leslie Meltzer, PhD, chief medical officer (CMO) at Orchard Therapeutics, “this is a relationship that needs to be cultivated from the earliest stages of development.”

Meltzer said companies need to consider what questions the patient communities might have about the safety and efficacy of therapy and how to motivate participation in a corresponding clinical trial. Meltzer advocates for early and frequent patient engagement with a unified voice on the value of a gene therapy product. This can be transformative in reaching communities and setting expectations about timelines and what’s involved with therapy.

The high price of one-shot cures

On pricing, Thomas Klima, Chief Commercial and Operating Officer of bluebird bio, discussed the pricing of the cell-based gene therapy product Zynteglo, approved by the FDA in August to treat beta-thalassemia, which will cost $2.8 million per patient. Klima highlighted that people with the most severe form of beta-thalassemia live their lives tethered to the healthcare system. They require regular transfusions and spend ​an average of 9.8 hours every three to four weeks in a hospital to receive the blood transfusions necessary for survival. Klima claimed that lifetime treatment for transfusion-dependent thalassemia costs more than $6 million—which is in line with the projection of $5.4 million from a recent study by Vertex—and argued for the value of bluebird’s treatment for $2.8 million.

For how commercialization models can expand and evolve, Christine Fox, president of Novartis Gene Therapies, said that part of the equation is bringing these treatments to countries around the world. At the heart of this problem is bringing patient advocacy and medical advisory to countries greatly affected by the clinical indication.

Overall, there was optimism that there would be an upswing in approved gene therapy products, as evidenced by a growing number of clinical trials using CRISPR gene editing. The first-ever approval of a CRISPR gene-editing therapy could be less than a year away. At the same time, base editing has already entered the clinic, and the first in vivo CRISPR approaches are progressing in clinical trials. This progress reflects how much has been learned in assembling the necessary pieces to get these treatments to commercialization, from development and manufacturing to the clinical and regulatory side of the equation.

More than one way to skin a [gene editing] cat

Another interesting session at the Cell & Gene Meeting on the Mesa offered forecasts of near- and longer-term future breakthroughs in clinical genome editing, featuring the CEOs of LogicBio, Homology Medicines, and Arbor Biotechnology as well as the CSO of Editas Medicine.

Devyn Smith, PhD, CEO at Arbor Biotechnologies, said investors understood the promise of genome editing, noting that the valuations of key public companies have held up “remarkably well” considering the market turmoil over the past two years. “[It] is incumbent on all of us in this space to continue executing and hopefully generating positive clinical data so that momentum continues,” Smith said.

Mark Shearman, PhD, CSO at Editas Medicine, agreed. “With any new technology, the [focus is] on clinical data and proving that it’s safe and efficacious. Typically, [investors] also want to see a projection of where the program’s going and a timeline over which you’ll be able to submit an application. They’re also interested in whether you are in control of the technology and have all the infrastructures to monitor the technology to be confident that you can advance it. Lastly, if you have examples where a regulatory authority has reviewed your process and analytics, confidence boosts when approved or accepted.”

Tim Farries, PhD, Principal Consultant and Senior Director with the consultancy Biopharma Excellence, also questioned the benefit of launching gene editing programs on rare diseases with small populations to show the relative ease and benefits before expanding to broader indications and populations. But for the most part, genome editing involves modifying DNA at one specific site. “That’s why you see gene editing therapies in monogenic disorders right now—because you have to know exactly what part of the genome is contributing at a big effect size to the disease that you’re trying to treat,” said Albert Seymour, PhD, President and CEO at Homology Medicines. “That’s a great place to start as we understand a little bit more about larger monogenic indications.”

During a discussion on choosing between developing editing tools or understanding biological targets, all panelists hedged towards editing technology. Fred Chereau, president and CEO of LogicBio, favored starting with the editing technology because it’s where the safety concerns can emerge. Understanding an editing technology’s efficiency and precision helps inform product development.

That said, each disease will require a different approach. According to Smith, certain indications will require a “cut-and-kill” approach to knock out or down a gene, changing an individual base or a series of bases, or impacting regulatory regions. “The reality is there are going to be a lot of different ways we’ve got to skin this cat, and it’s not going to be one-size-fits-all,” said Smith.

Another question addressed what payers would like to see gene editing show over the next three to five years. Shearman answered, “For the rare disease area, this should get worked out pretty quickly because, ultimately, [it] won’t be an issue of money based on the number of patients. I think the transition to treating large patient populations is going be an interesting one.”

Smith said that someone could be wildly successful and completely upend the payers’ way of doing things. “It’s an opportunity for new upstarts to come in and figure out new different approaches to innovate,” he said. On trying to fit the current approach to reimbursement into the one-and-done therapies, Smith added, “it’s not even a ‘square peg-round hole’—they’re in different planets. Something has got to give somewhere.” This will require different thinking because applying existing models will limit access to patients.

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