Experts say the time is now to develop and provide widespread access to genetic medicines for the rarest diseases. What’s more, they say it is a moral imperative.
With genome sequencing becoming cheaper and more accessible, the door to personalized genetic medicines for devastating diseases is cracking open and companies like EveryONE Medicines and Cure Rare Disease are determined to walk through, making such therapies commercially viable in the process.
“This is a new sort of paradigm, the individualized medicine paradigm,” said Julia Vitarello, co-founder of EveryONE.
Vitarello founded EveryONE after her daughter Mila was diagnosed in 2017 with Batten disease, a rare, fatal neurodegenerative disorder primarily affecting children. Vitarello wasn’t about to just accept the terminal diagnosis. Ultimately, she connected with Timothy Yu, a physician at Boston Children’s Hospital, who developed Milasen, an antisense oligonucleotide (ASO) tailored to Mila’s unique mutation. Mila was the first person in the world to receive a treatment designed for just one person, according to the company.
While effective, the treatment came too late in the disease process to save Mila, but Vitarello is committed to making individualized therapies—beginning with ASOs—available to all children with rare and ultrarare diseases involving unique genetic mutations.
Today, “we actually have the ability to find the patients like Mila, and if we wanted to, we could find them at birth. We could find them in utero if we wanted to,” Vitarello told BioSpace. And “the technology is allowing us now to recategorize patients by their underlying genetic cause.”
Experts who spoke with BioSpace called the development of personalized genetic medicines a moral and social imperative. The primary challenge, they agreed, is commercial viability.
A Problem of Scale
The current paradigm in pharma is characterized by large companies researching and developing medicines that can be used on “dozens, if not thousands, if not tens of thousands of people,” said Kent Rogers, the newly named CEO of EveryONE.
Rare diseases don’t fit this model. “There’s a number of diseases that are just not commercial in nature, meaning they won’t get the catalytic early-stage investment dollars to start the work and then usher and support it through to clinical trials and to commercialization,” said Rich Horgan, founder and CEO of Cure Rare Disease (CRD). Horgan founded CRD six years ago in an effort to help save his younger brother, Terry, who suffered from a rare form of Duchenne muscular dystrophy.
Terry Horgan died in 2022 while participating in an N of 1 trial for a novel CRISPR therapy, but like Vitarello, Rich Horgan is carrying on with his rare disease-related work. His aim is to help patients with muscular dystrophy disorders and spinocerebellar ataxia type 3 (SCA3), a rare neurodegenerative disease.
“What it gets down to is a massive problem of equity,” Horgan told BioSpace. “The family that doesn’t have the network, that doesn’t have the affluence” won’t be served by that paradigm.
Rogers pointed out that individualized therapies do have one notable advantage. Many currently approved drugs don’t work for 100% of the target patient population, while in contrast, with individualized therapies, “the chances of that medication working are exceptionally high, if not almost guaranteed, that it’ll have some . . . desired effect in that patient because you’re working with their genetic code,” Rogers said. “Doing that at scale and becoming profitable is what we’re going to try to solve.
“Ten years ago, I don’t know that this really would have even been possible or that we would have been able to try,” he continued. Today, it could be. “Genome sequencing costs have dramatically declined, and in fact, will likely decline to the level of just a routine blood test in the near future. That makes getting the whole genome sequenced very accessible,” Rogers said. This, he added, will make rare disease patients a lot easier to find.
And genome sequencing is far from the only recent scientific advancement.
Dan O’Connor, director of regulatory and early access policy at the Association of the British Pharmaceutical Industry (ABPI) who works closely with EveryONE, pointed to the reproducibility of platform technologies like ASOs and messenger RNA. “You could use that technology for multiple patients. You just have to change a particular aspect to it,” he told BioSpace. “That’s where the scalability could come in.”
What is needed, Vitarello said, is “a bustling ecosystem” of biotechs, academics, physicians, pharmaceutical companies and others focused on developing “thousands of drugs, each for small numbers of people.”
Building a Financial Foundation
Many of the current efforts to treat rare and ultrarare genetic diseases are grassroots. Much of the early financing for CRD came from event-based fundraising and grant writing, Horgan shared. But incentivizing more companies to get into this space requires a viable business model.
A key challenge, Horgan and Vitarello agreed, is developing a mechanism for reimbursement of these personalized genetic medicines. One potential pathway to reimbursement, Horgan said, is to treat these therapies as a procedure instead of as individual products that need to go through the traditional FDA review cycle.
Vitarello similarly suggested moving toward a surgery model where there wouldn’t be a need to file an investigational new drug application “and spend two years and millions of dollars” to develop a therapy. Instead, there would be accredited clinicians and partners and a highly individualized clinician-patient/parent consent process. “That then allows for the payers, I think, to come to the table,” she said, because the treatment is done at scale, with appropriate safety requirements, with less money spent.
But Nessan Bermingham, operating partner at Khosla Ventures, which is a founding investor in EveryONE, is less concerned about payer reimbursement. “They already pay for these types of medicines,” Bermingham told BioSpace, citing precedents with currently available gene therapies and CAR T therapies.
For payers, there is “a very high cost to actually treat these patients and maintain and address and deal with continued deterioration within these individuals,” Bermingham said, whereas personalized therapies are often one-and-done, saving costs over a patient’s lifetime.
Manufacturing is also key to making individualized therapies a reality, Horgan said. Because of the low patient numbers, centralized manufacturing isn’t appropriate. “One potential avenue may be decentralized manufacturing, where we have academic GMP units producing material at a much more affordable cost,” he suggested.
O’Connor said there is currently a convergence of technology and interest in personalized genetic medicines. “I think we’re at a really nice crossroads where we’re building the policy and strategy view that we’ve really got to do something, we’ve got to make some changes to the system.”
Making personalized genetic medicines possible is a matter of choice, Vitarello added. “If we do not build the infrastructure that’s needed to connect patients, any patient that is alive . . . that could benefit from a technology that exists today. . . . If we don’t create the infrastructure for that, it’s not that we can’t do it, it’s that we’re choosing not to do it,” she said. “That is a moral imperative, and that is how the world has changed in the past.”
