When bluebird bio’s gene therapy to treat beta thalassemia won European approval in 2019, the nearly $2 million per patient price tag for the potential cure seemed like a surmountable hurdle.
Fast forward two years later, and bluebird has withdrawn Zynteglo, the beta thal drug, along with the rest of its gene therapy portfolio from Europe, which the company said is generally unwilling to pay a fair price for the treatment.
In Germany, the only country for which bluebird disclosed details, authorities offered $790,000 for the one-time treatment, with the payout moving to $950,000 if the therapy is still working after five years. That’s roughly in line with the $900,000 price tag Wall Street analysts expected bluebird to put on the therapy prior to launch. But bluebird wanted $1.8 million paid over 5 years, with payouts conditioned on a patient’s response.
This and other examples (see Glybera) have raised questions about the viability of the gene and cell therapy space, particularly as it’s able to target smaller and smaller groups of patients.
Peter Marks, director of the center at FDA that regulates these therapies, addressed this issue of financial viability head on at a conference on Tuesday morning, particularly as it relates to indications where there may only be several dozen patients worldwide.
The problem is sponsors are seeing this group of only 20 to 40 patients per year for one therapy as commercially nonviable, Marks explained. If there was better manufacturing of smaller batches of AAV vectors for gene therapies, for example, he said, there might be a way to put together a portfolio of these smaller-population products that would then be viable.
While it’s unorthodox for any senior FDA official to address the commercial viability of any medical products, and the FDA recently addressed some of the safety question marks around gene and cell therapies, Marks specifically addressed these smaller groups of gene therapies, noting, “We’re all a little gun-shy when we see programs being dropped, and that means we have to find a way forward to restore confidence for these smaller populations.”
Part of the path forward includes figuring out how to price these expensive and expensive-to-make therapies, he said.
“Reimbursement is the 800 pound gorilla in the room,” Marks told the crowd virtually on Tuesday at the ASGCT’s 25th annual meeting in Washington, DC, noting that some of the accelerated approvals “make people shudder because of concerns” about pricing and risk-sharing models.
“Once there are 5 to 8 gene therapies, things will work themselves out,” Marks added, offering the example of Novartis’ spinal muscular atrophy gene therapy Zolgensma as a case where:
the value proposition is so overwhelming, it’s hard to think of not to cover that. But for others, where it’s not a life or death issue, it will be more challenging and will be similar to what our European colleagues see. How that gets resolved will completely affect how many people go into this field to develop therapies.
He also suggested a much more internationally harmonized approach for regulating these gene therapies for smaller, rare disease patient groups, which might have dozens of patients globally.
Marks suggested a way to move to a more common application process globally, noting, “Maybe we won’t get some of the preclinical info we do care about, but can live without, and in turn, patients get access in home countries without having to travel” to gain access to these therapies. “We have to give serious consideration to these products. If it’s designed to 10-20 per 100 million people, any one country won’t have enough patients to sustain commercialization,” he said.
Marks previously penned an NEJM editorial on these individualized treatments and how to regulate them in 2019.
On questions related to accelerated approval reforms, which have been in the news as Congress attempts to tack several of these reforms onto must-pass FDA user fee legislation, Marks said there’s a need for the AA pathway in the cell and gene therapy space. Some neurodegenerative diseases, for instance, he said, “If we take away the ability to use surrogate endpoints, we would have a lot of trouble seeing these products developed.”
But he did acknowledge that the accelerated approval pathway “has been used like an off-ramp” leading to problems in the past.
“Surprises are not needed here in the gene therapy field. The idea here is agreeing upfront on the surrogate, there’s less a chance for surprises. What we will be doing is moving these discussions upfront,” Marks said.
In response to a question from the audience on what the timetable might look like for getting back to teleconferencing between CBER and sponsors, Marks acknowledged the staff shortages and that this “is not an optimal situation. Even prior to the pandemic, we were understaffed. My key for 2022 is a recovery theme — my hope is that as we ease into the next calendar year, more robust exchanges with the agency occur, including teleconferences.”
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