Every Cure’s drug repurposing could change rare disease treatment

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There are more than 10,000 rare diseases and 95% of them have no cure. It can cost billions of dollars and take more than a decade to develop a new treatment. Because patient populations in the rare disease field can sometimes consist of only a few thousand or even a few dozen people, pharmaceutical companies are hesitant to invest so much time and capital into developing a drug that is unlikely to turn a profit.

drug reuse it inverts the model. Repurposing looks for new ways to use existing drugs to treat diseases for which they were not originally designed. And there are now groups using artificial intelligence to make this process more efficient.

Dr. When David Fajgenbaum and his colleagues were considering starting Every Cure, a nonprofit focused on drug repurposing, they had a big decision to make.

“If you want to repurpose drugs, there are two ways you can go. The first is to open our shop and have patients and disease groups come to us and say, ‘Hey, are you going to find a drug for my disease?'” Fajgenbaum said. “We’ll let him say it,” you can say. he said. “Or you take another approach… using AI to basically find the low hanging fruit among all the drugs and diseases.”

Fajgenbaum and his co-founders chose the second option.

Every Treatment It does not seek a specific treatment for a particular disease. Instead, it looks at whether there are existing medications that can help any existing disease. The group searches for drug-disease matches and connects with patients who could benefit. This marks a major departure from the way rare disease treatments have traditionally been developed.

“The way research has always been done, if you want someone to do your research, you go to them, you pay them,” Fajgenbaum said. “People come to us and say: we want you to work on our disease, here’s the money, and we said ‘no, no, no, we can’t… we don’t do it that way.’

“It’s been a little bit difficult to spread that message,” he added.

So despite Fajgenbaum’s long history of finding existing drugs that are effective treatments for rare diseases (he estimates his work has helped save the lives of more than 1,000 patients in the past 12 years), finding funding hasn’t been easy.

“We didn’t raise any money our first year,” Fajgenbaum said.

Rare disease philanthropy is often deeply personal. Donors often want to support research on a disease that affects their own family.

Although there were several early proposals to fund research into drug repurposing for diseases such as pancreatic cancer, Every Cure’s approach was disease agnostic. This meant Fajgenbaum had to distance himself from any donors who wanted to fund specific disease treatments.

“We had literally dozens of pitches in the first year and turned down a lot of money. But we felt it was the right thing to do,” Fajgenbaum said. “I didn’t want to be in a situation where we were accepting funds … and we spend five years and $5 million of someone’s money and come up with nothing.”

But Fajgenbaum found partners willing to fund Every Cure’s disease-neutral approach. The Chan Zuckerberg Initiative was an early supporter. Such as Lydia Hill Foundation, Flagship Pioneering and Arnold Ventures.

Eventually, Every Cure was able to secure a $60 million commitment from TED’s Audacious Project and gained access to more than one. $130 million It’s from two separate rounds of funding from the Advanced Health Research Projects Agency, or ARPA-H, a federal funding agency established by the Biden administration in 2022.

The first results look promising. Since Every Cure was founded in late 2022 10 active programs in drug repurposing portfolio.

“We spent the first year fundraising and basically building the funds. The second year is building the team. The third year is really developing that pipeline,” Fajgenbaum said. “We expect most of these 10 active programs to reach patients.”

Fajgenbaum’s goal for the foundation is to be able to treat 15 to 25 diseases with redesigned drugs by 2030, and he and his team have a track record of success. Before launching Every Cure, the group’s leadership was responsible for repurposing 14 drugs for five different diseases.

The power of artificial intelligence in disease research

Fajgenbaum’s success find medicine It was the result of examining his own blood samples, reviewing thousands of scientific papers, and experimenting on himself with this breakthrough, which could be repurposed to treat Castleman disease, a rare, often fatal disease from which he suffers.

However, Every Cure uses artificial intelligence to streamline the process.

Each month, the group’s technology team scores nearly 4,000 existing drugs on how effective they would be in treating more than 18,000 known diseases; approximately 75 million possible matches. Three years ago it would have taken 100 days to create this list. Now it takes about 17 hours.

A medical team then examines the most promising leads and narrows them down with deeper analysis to determine which are the best treatments to pursue. Each Treatment will only pursue treatments that have both the potential to be effective against a devastating disease and appear financially viable for the organization to advance to the clinical trial phase; this costs between $3 million and $7 million per drug.

Every Cure’s goal is not just to publish this information, but to lead medicine through what comes next: laboratory studies, trials, regulatory discussions, educating doctors, and finally bringing these treatments to patients who could benefit from them.

“We are extraordinary because we are top-notch,” Fajgenbaum said. “We don’t just want to find a match and publish it. We want to publish it, then do the work to prove it, and we want to do the work to find the people who need it.”

To demonstrate the effectiveness of this approach, Fajgenbaum pointed to Every Cure’s study of Bachmann-Bupp syndrome, an extremely rare neurodevelopmental disorder first diagnosed in 2018.

Working with the same researchers who first described the condition, Every Cure found that a drug developed decades ago for African sleeping sickness inhibited the protein that causes the disease.

Fajgenbaum says six people, five of them children, have been treated with the drug so far, and all five children have shown significant improvement: sitting upright, interacting more with loved ones and, in some cases, achieving gains that once seemed elusive.

“That’s why we founded Every Cure,” he said.

Comparison of repurposing and new drug development

Fajgenbaum does not see drug redesign as a substitute for new drug development in the field of rare diseases. It simply recognizes that there are many diseases that could benefit from new treatments and is actively seeking to collaborate with partners developing these new approaches. However, Fajgenbaum believes that both options should proceed in parallel.

“I truly believe it is both,” he said. “We need people to continue to find new drugs, and we need to make sure that there is an entity that looks at all the old stuff. … We don’t think every disease can be treated with an existing drug, we think every disease that can be treated with an existing drug should be.”

Fajgenbaum counters with data critics who say investing in repurposing means taking money away from research to develop new drugs.

“Creating a brand new drug costs $1 billion or $2 billion. That takes 10 to 15 years,” he said. “We’ll probably always be a part of that.”

But Every Cure ran into another problem when finding uses for old drugs that no longer provided a strong financial incentive for drug companies to produce them.

“In some cases, if the drug is still patented, a pharmaceutical company may not even want to manufacture it anymore, because it’s not even a break-even point. In fact, it would cost more to produce it than they would produce it,” Fajgenbaum said. “We have this situation right now in one of our programs. It’s a big pharmaceutical company. I’m trying to convince them that this is the right thing to do.”

As Fajgenbaum puts it, “The medical system works when there’s a new drug. The medical system doesn’t work when there’s an old drug.” He argues that if a treatment becomes generic, “it is not profitable to find a new use for the drug.”

This gap is exactly where Every Cure believes it has a role. In rare diseases, where time is valuable and commercial incentives are often limited, re-evaluation as a second path, as well as the search for brand new treatments, can save lives that do not need to be lost.

But moving these discoveries through the regulatory system hasn’t been easy either.

Each Treatment still faces an FDA approval process centered around the traditional sponsor model. “In our discussions with the FDA, there is no sponsor because the people who produce the drug are not interested in it,” Fajgenbaum said. “We are an independent, nonprofit organization,” he added, describing how unusual that might seem to regulators accustomed to dealing with drugmakers. “‘Then why are you here?’ they say. Because it will benefit children!'”

That’s why educating doctors has become such an important mission for Every Cure. FDA approval is not always required for a redesigned drug to reach patients. Doctors may prescribe medications off-label and for rare diseases that occur frequently.

Still, Fajgenbaum said, getting the FDA stamp of approval helps: It makes the insurance process smoother, gives doctors and patients more confidence in the treatment and increases general awareness of the drug’s effectiveness.

But despite all the obstacles Every Cure faces, the group continues to take new steps, and Fajgenbaum says the efforts are worth it. “You want to repurpose drugs to save lives, which is all we care about. That’s literally the only reason we do this…to save and improve lives,” he said.

For rare disease families accustomed to hearing that their disease is too minor, too complex, or financially unattractive, Every Cure is building something rare in its own right: a system that looks the part anyway.