In a landmark announcement, the U.S. Food and Drug Administration on Dec. 8 approved the gene therapies Casgevy and Lyfgenia to treat sickle cell disease. Casgevy is the first FDA-approved therapy utilizing CRISPR/Cas9 genome editing technology.
As the government official responsible for approving novel genomic therapies, Peter Marks spoke enthusiastically about CRISPR with National Press Foundation’s Covering Rare Disease fellows just weeks before its approval.
“It’s really remarkable to see something that was discovered and described in 2012, that’s now made its way through the clinic to an FDA submission,” said Marks, the Director of the Center for Biologics Evaluation and Research. His remarks came one day after officials in the United Kingdom approved the novel gene therapy, which successfully ended life-long agonizing sickle cell symptoms for Victoria Gray, the Mississippi woman who is the first in history to undergo CRISPR therapy.
The journalists received exclusive insights into the research and regulatory process for moving potential treatments for rare diseases from the research realm to the real world. The following quotes are highlights from his presentation.
Peter Marks take on CRISPR therapy: ‘Exciting times’
“It’s quite a remarkable product because the data seems to indicate that it’s capable of essentially alleviating the major symptoms of sickle cell disease.”
He said the system has been “refined” to now allow many edits to a genome.
“What CRISPR-Cas9 did was make this into a much more efficient process and also a much more elegant one.”
The do’s and don’ts of genomics
“In terms of the regulatory considerations, when we think about genome editing, we think about the nature of the editing that’s being done, where it’s being done – either outside of the body or inside of the body – and what’s being done. Are you inactivating a gene, inserting a sequence or modifying sequence?”
If done outside the body, they must “understand before you give cells back, that you haven’t done anything nasty to them that might alter some other place in the genome.”
“The issue with CRISPR-Cas9 genome editing is this concern that because the genetic changes are guided by genetic sequence, which could potentially sit down at the wrong place on a very large genome, the potential for off-target effects – in other words, cutting in places or making changes in places that you don’t want – is one we have to be cognizant of.”
Lack of diversity is a drain on progress
“There is really a drought of clinical research in Africa … in India and in the countries in that area of Asia, there’s inadequate study of these products.”
“Although yes, these products are expensive and are currently being developed in high-income countries, their potential applicability is very much in low and middle-income countries,” Marks said. “If you have beta thalassemia major and you’re in Western Europe or in the United States, you can get transfused with blood on a regular basis. You can get iron chelation therapy to get rid of the excess iron that all of those blood transfusions cause. You can get good perinatal care … We have that in Western countries, in high-income countries. The problem is in places in many parts of the world that are low or middle-income countries, there’s no such supportive care, so their survival is pretty dismal.”
“There is a gene therapy that is one and done, that could be unusually transformative from what is otherwise essentially a death sentence to something that would be quite survivable. … This issue of health equity, especially as we come into more and more gene therapy, will be a large one.”
Navigating the winds of change
The venture capital that went into gene therapy and biotech several years ago is “drying up,” Marks said.
“There was a lot of promise, and perhaps what might be characterized as some hype. Reality has set in with capital drying up, as well as realization that [gene therapies] aren’t easy to make. The clinical development is not as quick as people had sometimes hoped. The ability to have markets here globally, it can sometimes be challenging because of different global regulatory requirements. These have combined to put some challenges here.”
“Our goal at the Center for Biologics is to try to help get products to patients to help address some of these, so that products don’t fall out of development that could potentially be helpful to people. We are working to try to advance the manufacturing of gene therapies through internal research and through external funding of certain projects.”
Access the full transcript here.
This training was sponsored by Fondation Ipsen. NPF is solely responsible for the content.
