Extending the reach of gene therapies means hurdling not just scientific barriers but prices, too

While Covid-19 struck a blow to a vast number of clinical trials around the world, the pandemic may turn out to be a boon for bringing gene therapies to more people in the coming years.

“Who would have predicted three years ago that we’d now be having billions of doses manufactured of mRNA packaged in a lipid nanoparticle?” Sekar Kathiresan, CEO of Verve Therapeutics said Tuesday during the STAT Breakthrough Science Summit

Verve is currently developing a base editing therapy for a genetic form of heart disease. Similar to the vaccines produced by Pfizer and Moderna, it involves delivering mRNA enveloped in tiny balls of fat. “The manufacturing capacity for those constructs has been expanded dramatically in the last year, so a product like ours, when we get to market, will benefit a lot from that scale happening right now,” said Kathiresan.


The hope is that with improved economies of scale, the next generation of gene therapies may not be as expensive as the ones currently on the market. Zolgensma, for example, a gene therapy approved in 2019, is the world’s most expensive drug at $2.1 million.

But boosts to mRNA and lipid nanoparticle manufacturing won’t be a magic bullet for issues of patient access. Verve’s lead candidate involves “in vivo” gene editing, that is, altering the DNA of cells from inside a patient’s body. (An important first test of this technique was recently achieved by Intellia Therapeutics, with its CRISPR fix for an inherited nerve disorder.)


But many gene therapies in development do something different: deliver genetic fixes to cells collected from patients before infusing them back in. Orchard Therapeutics is one of many companies working on these “ex-vivo” approaches, for patients with rare genetic diseases. A critical step in the process is conditioning, which removes a patient’s defective bone marrow cells and makes space for the newly corrected cells to engraft. But because it leaves people without as many blood cells as they should have, it often relegates them to weeks in the hospital for careful monitoring. After that, they have to go to a bone marrow transplant center, with specialized physicians and staff to oversee the final step — infusing a patient’s genetically corrected cells back into their bodies. 

“I think that’s one of the challenges we will see coming up,” said Kathy High, president for therapeutics at AskBio. Multiple companies are currently testing gene therapies and CRISPR-based medicines for treating sickle cell disease, one of the most common genetic disorders. Currently, there are about 100,000 people living with sickle cell disease in the United States, said High. “We do about 25,000 bone marrow transplants a year, and those 25,000 people aren’t going to stop needing them. So how is the system going to reconfigure itself to accommodate the demand in that setting?”

While that concern might only apply to the ex-vivo crowd, one issue of access is being felt by everyone in gene therapy — that of reimbursement. 

“Again there, you’re challenging paradigms, because here you have a one-off therapy that has the potential for lifelong change when you have reimbursement models set up for chronic therapies,” said Bobby Gaspar, CEO of Orchard Therapeutics. But he remained optimistic that like every other emerging medical modality, it will get easier over time. 

“As we’re pushing forward the boundaries and developing new medicines, we have to cross those hurdles and sometimes it’s not so easy because you’ve got to get it right, but the more you get it right the more you get it right further down the line. It’s important to remember there’s only a handful of approved gene therapies, but as more get approved we won’t face these same hurdles with reimbursement and access.”

Source: STAT