Maggie Carmichael wasn鈥檛 developing like other kids. As a toddler, she wasn鈥檛 walking and had a limited vocabulary for her age.
She was diagnosed with PMM2-CDG, potentially fatal gene mutations that cause abnormal enzyme activity 鈥 and affect worldwide. Her parents, Holly and Dan Carmichael, raised $250,000 for scientists to screen existing drugs to find a potential treatment, and in a single-patient trial with Maggie as the test subject, one drug showed . The young girl stopped face-planting when crawling, she began using a walker instead of her wheelchair, and her lexicon expanded.
The Carmichaels and their organization, Maggie鈥檚 Cure, could have handed off the work to a biotech company. Instead, the family from Sturgis, Michigan, formed a joint venture partnership with Perlara PBC, a San Francisco company that tries to identify new and existing drugs to treat rare diseases. The Mayo Clinic would later join as a co-owner of .
The company secured 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 defy what doctors told the Carmichaels about the prospects of a treatment when Maggie was diagnosed at 9 months:
鈥淣ot a snowball鈥檚 chance in hell.鈥
, and their families have long pushed to speed up cures, usually by forming foundations that seed money for research. If there are promising findings, many hand the work off to biotech companies to develop treatments. Now, some families are forming their own biotech businesses, acting as drug developers to find treatments for ultra-rare diseases that affect 1,000 patients or fewer.
But their chances are slim.
Only about are ever approved by the FDA. And few biotech firms focus on rare diseases given the limited size of the patient market; of clinical trials are focused on rare diseases.
This means families aren鈥檛 likely to find a cure 鈥 let alone make a profit.
鈥淚f a drug should get approved for a disease with 1,000 patients, the probability that there are any material profits, I would say, is actually remote,鈥 said James Geraghty, who is on biotech boards and is the author of 鈥淚nside the Orphan Drug Revolution: The Promise of Patient-Centered Biotechnology.鈥
But families say cures, not profits, motivate them.
According to the National Institutes of Health, there are rare diseases, affecting nearly 1 in 10 Americans. A rare disease is generally considered one that affects fewer than in the U.S. at a given time. Only with rare diseases will live to see their 5th birthday.
Some are without an FDA-approved treatment or therapy.
Upon a child鈥檚 diagnosis, parents will often quit their jobs and reorder their lives to find a treatment. Families will use their own money or raise funds to enter the arena. Dozens, if not hundreds, of nonprofit family foundations across the nation focus on rare-disease treatments amid the dearth of public and private funding.
Drugmakers can charge exorbitant , so it can be highly profitable to like cystic fibrosis, which affects up to . But the market becomes much less attractive for ultra-rare diseases because of the much smaller pool of patients.
鈥淚t鈥檚 the riskiest of the risky,鈥 said Joe Panetta, CEO of Biocom California, a life sciences trade group.
Drug regulations prohibit the Carmichaels from sharing how Maggie is doing now because of the clinical trial, but Maggie鈥檚 Pearl, assuming its drug earns FDA approval, says it aims to ensure the treatment can be accessed by all with the disease.
The Carmichael family is helping to pay for a clinical trial it estimates will cost $3 million to $5 million. The family won鈥檛 say how much it鈥檚 contributing, but $2 million is coming from a federal Small Business Innovation Research grant.
Holly Carmichael, chief operating officer of Maggie鈥檚 Pearl, says she鈥檚 motivated to shepherd a drug鈥檚 development while keeping prices lower than they might otherwise be. 鈥淲e鈥檙e not a traditional biotech with shareholders that have certain profit thresholds,鈥 she said.
The company has pledged to reinvest a portion of its profits into research and development. The rest would flow to the venture鈥檚 owners, including the Carmichael family.
In that way, Maggie鈥檚 Pearl is 鈥渏ust like any other business,鈥 said Ethan Perlstein, the CEO of Maggie鈥檚 Pearl and Perlara, which counts Swiss drug giant Novartis AG and entrepreneur Mark Cuban among its early investors. Convicted pharmaceutical executive in Perlstein鈥檚 venture.
Last month, a Boston company called Vibe Biotechnology announced a to raise money for rare-disease drug development. Investors will have the power to vote on rare-disease research proposals, and patients鈥 families have ownership stakes in promising therapies.
鈥淭he challenge for rare diseases isn鈥檛 necessarily finding a treatment 鈥 it鈥檚 funding it,鈥 said Alok Tayi, CEO and co-founder of Vibe Biotechnology, in a statement. 鈥淔or the first time, Vibe Bio is giving patients with rare and overlooked diseases access to the funding and community support they need to develop cures and ownership over the results.鈥
The company has launched two biotech companies in partnership with two foundations: , which is focused on Lafora disease, a fatal form of progressive myoclonus epilepsy, and , which hopes to accelerate a gene therapy for neurofibromatosis Type 2, which causes the growth of noncancerous tumors in the nervous system.
One reason more families strike out on their own is for greater control.
Typically, if research advances far enough, families entrust biotech companies to bring drugs to market. A company usually gains intellectual property rights as part of taking on the financial risks of developing such treatments. But if that company shelves the program, parents are left helpless and heartbroken.
The Cure Mito Foundation 鈥 along with other family foundations 鈥 funded research in Steven Gray鈥檚 lab at the University of Texas Southwestern Medical Center.
Taysha Gene Therapies, a company formed in 2019, pledged to accelerate Gray鈥檚 research and take financial pressure off families. In return, Taysha gained potentially lucrative and controls the rights to these programs.
In March, Taysha announced it would cut 35% of its staff and shelve much of its portfolio, reflecting an . The pause included Cure Mito鈥檚 campaign to develop a treatment for Leigh syndrome, a neurogenerative condition that leaves some children unable to walk and breathe on their own.
Taysha鈥檚 pause has worn on Courtney Boggs, a member of the Cure Mito Foundation. Her daughter, Emma, is a cheerful 6-year-old who loves reading and playing with dolls. She eats through a feeding tube and cannot walk unassisted, and her condition will worsen without treatment.
鈥淲e need something for our kids, and not just our kids, but future generations,鈥 said Boggs, who lives in El Paso, Texas.
Taysha, which is among a small number of companies investing in treatments for ultra-rare disease, narrowed its focus from more than 20 to four rare-drug programs.
鈥淲e share the disappointment and frustration of our patients and their families right now,鈥 the company said, 鈥渂ut truly believe the tough decisions we are making today will best position us to conduct new trials in the future.鈥
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 claw back rights to medications 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 treatment for their 19-year-old daughter, Christiane, who suffers from Batten disease, which causes vision loss and seizures.
The Bensons鈥 foundation funded a therapy that the French pharmaceutical company Theranexus licensed in 2020 and is in early-stage clinical trials. As part of the deal, Theranexus shouldered development costs and paid the foundation an undisclosed upfront sum. The foundation may receive additional payments and royalties on sales if the drug wins regulatory approval. Beyond Batten is reinvesting its money to search for additional treatments that could complement the potential therapy.
鈥淲e鈥檙e not reliant on bake sales,鈥 Benson said.
This story was produced by , which publishes , an editorially independent service of the .
