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‘This is not a science problem anymore': Paths emerge for scaling up rare disease medicine

Jared Whitlock (Endpoints News)

July 27, 2023

In 2014, the National Institutes of Health posted an estimate that at the current pace of drug development and approval, it would take 1,000 years to get treatments for the 7,000 known rare diseases.

A paper at the time suggested speeding up that work by grouping together similar diseases, and then treating these patients with the same therapy in a single clinical trial.

A similar idea — and other ways to go faster — are now getting closer to reality, pushed forward by new technical, economic and regulatory approaches. The framework is being created by companies like Moderna, by scientists who developed custom therapies that have the potential to benefit a larger population, and by a mother who knows the pain when a medicine doesn’t arrive in time.

Since 2014, the FDA has cleared 180 therapies for rare conditions. But the science has been especially slow to reach the rarest of rare conditions, where drugmakers struggle to eke out profits. Ninety-five percent of rare diseases still lack a treatment, a number that may be even higher amid genetic testing pointing to previously unknown rare conditions.

A system designed for something different

The 2014 paper on scaling was based on small-molecule drugs. But advances in gene editing and other plug-and-play technologies could provide an even quicker path.

“Our whole system is set up around developing one treatment for one disease. The idea of therapeutic platforms is one that’s coming along,” said PJ Brooks, acting director of the division of rare diseases research innovation at the National Center for Advancing Translational Sciences.

Brooks, one of the authors of the paper, is also involved in a $42 million NIH program calling for proposals to support gene editing multiple diseases in a single clinical trial.

Those multi-disease trials would change the sequence of the guide RNA — which shuttles CRISPR to the right spot in the genome — but keep everything else the same, including the gene editor and the route of administration.

Intellia Therapeutics is interested in the approach.

In March, the FDA approved Intellia testing its experimental CRISPR medicine for a rare disorder called hereditary angioedema, showing that the agency is increasingly willing to allow trials for therapies that edit genes in the body. And although that therapy is designed for a single disease, Intellia is hopeful that it’s a step toward quickly rejiggering its gene editing platform for other diseases.

“We have these modular components that now regulatory agencies have seen,” Intellia chief financial officer Glenn Goddard said.

Another push to scale rare disease medicines can be traced to Julia Vitarello’s plea to help her daughter, Mila. In 2017, it resulted in a landmark for the field: a treatment tailored to one person’s unique genetic mutation, developed in just under a year.

Mila’s drug halted her rapidly progressing condition, an ultra-rare form of Batten disease, and improved her quality of life over three years. Still, it was too late for the advanced-stage disease, and in 2021 Mila died at 10 years old.

Vitarello works from Mila’s old room — the sheets and fairy curtains still the same — on the company she co-founded, EveryONE Medicines. EveryONE is trying to make this type of drug development sustainable — or what she calls “Mila to millions.” The company has backing from venture capital firms like Khosla Ventures.

“This is not a science problem anymore. We have the technology to find the underlying disease cause and create a drug for it,” Vitarello said.

By technology, she’s referring to antisense oligonucleotides, which insert snippets of genetic code to patch genetic mutations. The genetic sequence can be easily changed — making the system programmable for targeting various diseases — and designed in such a way to reach a wider population.

The doctor who led the creation of Mila’s drug, Timothy Yu, showed in a recent paper that antisense drugs could treat up to 15% of patients with ataxia-telangiectasia, a rare condition made up of many mutations. And importantly, he estimated that not every individual would need their own custom-made therapy. Experts believe the findings could be a road map for more quickly developing treatments in other rare conditions.

In yet another approach, Moderna — which brings deep experience with regulators and scientific cachet — has aimed its mRNA technology toward rare conditions, including especially rare conditions like Crigler-Najjar syndrome type 1. It occurs when the liver cannot break down a substance created by red blood cells, causing children to die young.

“We’re going full steam in rare disease,” CEO Stéphane Bancel told Endpoints News in an exclusive interview last month.

All these technologies look to play a role amid a great need: One in 10 people have a rare disease.

Not just a finance challenge

Moving those sorts of treatments from the lab to patients will require different regulatory approaches. In draft guidance, the FDA relaxed testing requirements for antisense medicines aimed at only one or two patients. But rare disease advocates say much more could be done.

Whitlock, J. (2023, July 27). “This is not a science problem anymore”: Paths emerge for scaling up rare disease medicine. Endpoints News.



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