Maggie Carmichael was not developing like other children. As a child, he did not walk and had a limited vocabulary for his age.
He was diagnosed with PMM2-CDG, a potentially fatal gene mutation that causes abnormal enzyme activity — and affects fewer than 1,000 people worldwide. Her parents, Holly and Dan Carmichael, raised $250,000 to have scientists screen existing drugs to find potential treatments, and in a single patient trial with Maggie as a test subject, one drug showed promising results. The young girl stopped wearing a mask when she crawled, she started using a walker instead of her wheelchair, and her vocabulary expanded.
The Carmichaels and their company, Maggie’s Cure, may outsource the work to a biotech company. Instead, the Sturgis, Michigan, family formed a joint venture partnership with Perlara PBC, a San Francisco company that seeks to identify new and existing drugs to treat rare diseases. Mayo Clinic would later join as co-owner of Maggie’s Pearl.
The company received approval last December for a 40-patient clinical trial that could one day lead the FDA to approve the drug for PMM2-CDG. It would also negate what doctors told the Carmichaels about treatment options if Maggie was caught at 9 months:
“There’s no snowball’s chance in hell.”
Half of all rare disease patients are children, and their families have long pushed to speed up cures, typically by forming foundations that allocate money for research. If promising results are found, many hand the task over to biotech companies to develop treatments. Now, some families are forming their own biotech businesses, working as drug developers to find treatments for ultra-rare diseases that affect 1,000 or fewer patients.
But their chances are slim.
Only 12% of drugs in clinical trials are approved by the FDA. And some biotech firms focus on rare diseases because of the limited size of the patient market; 12% of clinical trials are focused on rare diseases.
That means families are unlikely to find a cure — let alone profit.
“If a drug should be approved for a disease with 1,000 patients, the chances of any material gain are, I would say, actually remote,” said James Geraghty, who is on the biotech board and author of “Inside the Orphan.” The Drug Revolution: The Promise of Patient-Centered Biotechnology.
But families say healing, not profit, motivates them.
According to the National Institutes of Health, there are about 7,000 rare diseases, affecting about one in 10 Americans. A rare disease is generally considered to affect fewer than 200,000 people in the United States at any given time. 30% of children with rare diseases will live to see their 5th birthday.
About 95% of rare diseases occur without an FDA-approved treatment or therapy.
After a child’s diagnosis, parents will often quit their jobs and rearrange their lives to find a treatment. Families will use their own money or fundraise to enter the field. Dozens, if not hundreds, of nonprofit family foundations across the country focus on treating rare diseases amid a lack of public and private funding.
Drugmakers can charge higher prices for drugs for rare diseases, so targeting rare diseases like cystic fibrosis, which affects 200,000 Americans, can be highly profitable. But the market for ultra-rare diseases becomes much less attractive because the number of patients is much smaller.
“It’s risky risk,” said Joe Panetta, CEO of Biocom California, a life sciences trade group.
Drug regulations prohibit Carmichaels from sharing how Maggie’s is doing now because of clinical trials, but Maggie’s Pearl, assuming its drug gets FDA approval, says it aims to make sure everyone with the disease can be treated.
The Carmichael family is helping to pay for a clinical trial that is estimated to cost $3 million to $5 million. The family would not say how much they are contributing, but $2 million is coming from a federal Small Business Innovation Research grant.
Holly Carmichael, chief operating officer of Maggie’s Pearl, said she was motivated to develop the drug and keep prices lower than otherwise. “We’re not a traditional biotech with shareholders who have certain profit thresholds,” he said.
The company has pledged to reinvest a portion of its profits into research and development. The rest will flow to the venture’s owners, including the Carmichael family.
In that way, Maggie’s Pearl is “just like any other business,” said Ethan Perlstein, CEO of Maggie’s Pearl and Parlor, which counts Swiss drug giant Novartis AG and entrepreneur Mark Cuban among its early investors. Convicted pharmaceutical executive Martin Shkreli was bought out of his initial stake in Perlstein’s venture.
Last month, a Boston-based company called Vibe Biotechnology announced a cryptocurrency-based model to raise money to develop drugs for rare diseases. Investors will have the power to vote on rare-disease research proposals, and families of patients have ownership in promising therapies.
“The challenge for rare diseases isn’t necessarily finding a treatment — it’s funding it,” Alok Tai, CEO and co-founder of Vibe Biotechnology, said in a statement. “For the first time, Vibe Bio is giving patients with rare and neglected diseases access to the funding and community support they need to develop cures and ownership over their outcomes.”
The company has launched two biotech companies in partnership with two foundations: Chelsea’s Hope, which focuses on Lafora disease, a fatal form of progressive myoclonus epilepsy, and NF2 BioSolutions, which hopes to accelerate a gene therapy for neurofibromatosis type 2. which causes this disease. Noncancerous tumor growth in the nervous system.
One reason more families strike out on their own is for greater control.
Typically, when research is advanced enough, families entrust biotech companies to bring the drug to market. A company typically acquires intellectual property rights as part of taking the financial risk of developing such treatments. But if that agency shuts down the program, parents are left helpless and heartbroken.
The Cure Mito Foundation – along with other family foundations – funded Steven Gray’s lab at the University of Texas Southwestern Medical Center.
Taysha Gene Therapies, a company formed in 2019, promises to accelerate Gray’s research and ease the financial burden on the family. In return, Taisha acquires potentially lucrative research licenses and controls the rights to these programs.
In March, Taisha announced it would cut 35% of its workforce and shed much of its portfolio, reflecting the industry’s downturn. These breaks include Cure Mito’s campaign to develop a treatment for Leigh syndrome, a neuroregenerative condition that leaves some children unable to walk and breathe.
Taisha breaks down on Courtney Boggs, a member of the Cure Mito Foundation. Her daughter, Emma, is a cheerful 6-year-old who loves to read and play with dolls. He eats through a feeding tube and cannot walk without help, and his condition will worsen without treatment.
“We need something for our kids, and not just our kids, but for future generations,” said Boggs, who lives in El Paso, Texas.
Taisha, which is among a small number of companies investing in ultra-rare disease treatments, has narrowed its focus from more than 20 to four rare-drug programs.
“We share the frustration and disappointment of our patients and their families right now,” the agency said, “but truly believe the difficult decisions we are making today will best position us to conduct new trials in the future.”
Other families are trying to prevent that scenario by securing more favorable terms when doing business with biotech companies, such as licensing payments and the ability to take back drug rights if drugmakers take too long.
Craig Benson, a finance executive from Austin, Texas, and his wife Charlotte formed the Beyond Batten Disease Foundation to find a cure for their 19-year-old daughter, Christian, who suffers from Batten disease, which causes vision loss and seizures. .
Benson’s Foundation funded a therapy that French pharmaceutical company Theranexus licensed in 2020 and is in early-stage clinical trials. As part of the deal, Theranexus covered development costs and paid the foundation an undisclosed upfront payment. The foundation may receive additional payments and royalties on sales if the drug receives regulatory approval. Beyond Batten is reinvesting its money into finding additional treatments that can complement potential therapies.
“We’re not dependent on bake sales,” Benson said.
This story was produced by KHN, which publishes California Healthline, the editorially independent service of the California Health Care Foundation.
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