For every million-dollar gene therapy, Peter Marks gets an email from FDA chief Robert Califf

After Orchard Therapeutics’ gene therapy for a rare genetic disease was approved in March, Peter Marks, M.D., Ph.D., received a simple email from Commissioner Robert Califf, M.D.  

“Every time we approve a new gene therapy, and then the company announces the price of the gene therapy, the commissioner sends me a note and it's usually [short]—I love short emails,” Marks told the crowd at the American Society of Gene and Cell Therapy annual meeting Wednesday morning. Marks serves as director of the Center for Biologics Evaluation and Research (CBER).

“The last one was a $4.25 million exclamation point," Marks recalled. "It was like a lot of exclamation points after. I can't remember how many, and that was the email. And I knew what it meant.” 

In March, Orchard’s Lenmeldy won FDA approval to treat the rare genetic disease metachromatic leukodystrophy (MLD). With the price tag of $4.25 million, the therapy quickly took the title of most expensive drug, taking a crown previously worn by CSL Behring and uniQure’s hemophilia B gene therapy Hemgenix, which costs $3.5 million before any discounts. 

Orchard said the price is “reflective of the value the therapy may deliver … as well as the potential long-term impact the treatment may have on overall healthcare utilization.”  

CBER does not consider prices in approval decisions for the therapies it reviews, Marks said. It’s just not part of the group's remit.  

“On the other hand, it's my job to look at the entire ecosystem," he commented Wednesday. "Step back independent of a given product and say, is this sustainable? In other words, can we ultimately have the field of gene therapy mature and start to treat more common diseases if we keep having to charge a million or $2 million for a dose?”

The FDA believes it can help with the pricing situation to some degree. Additional regulatory steps can add costs for biotechs, particularly smaller ones that are going after orphan diseases. So Marks says the agency has to streamline operations wherever possible. 

“We're very aware of this and understand that there are measures we can take by hopefully helping to improve manufacturing technologies, which would reduce costs by shortening the time to development so there are levers on the whole ecosystem we can take," the regulator said.

Without big changes to the cost of gene therapies, they will never go global, Marks argued. Improving access to gene therapy is above all the most important thing that can be done to reduce prices.  

“I come to work every day because we want to help more people and we want to help more people globally. The way we'll do that is ultimately by getting down the cost of these therapies. And if we can get down the cost enough, they may actually ultimately replace some conventional therapies,” Marks said.  

For example, one day a gene therapy could help everyday people sharply reduce their cholesterol.

For Marks, steep price tags also underscore the need for long-term patient follow-ups post-approval. Patients with diseases like sickle cell or beta thalassemia who are now eligible for gene therapies may be hard to catch up with once they receive treatment after years of dealing with chronic illness.  

“You can imagine that if you've been cured of your thalassemia or sickle cell disease, you might not want to but that follow-up is potentially very, very important going forward to understand continued benefit and any adverse effects,” Marks said. Following small populations of people with rare diseases can also be expensive, he noted.

Marks said the FDA will be thinking in the next few years about how to incentivize long-term follow-up data collection. This kind of real-world data could be crucial to proving value for payers. 

Even with huge million-dollar price tags, gene therapies that are approved for rare diseases and small populations will never reach the heights of spending currently going on with the GLP-1 weight loss/obesity craze, Marks said.  

“The truth is even if we approve an incredible number of these rare disease gene therapies … we're lucky that the amount that’s getting spent on GLP-1 agonists is so big, that we'll still not make a dent even close to that with the gene therapies,” Marks said.