At 15, Autumn Fuernisen is dying. She was diagnosed at age 11 with a rare degenerative brain disorder that has no known cure or way to slow it down: Huntington鈥檚 disease.
鈥淭here鈥檚 lots of things that she used to be able to do just fine,鈥 said her mom, Londen Tabor, who lives with her daughter in Gillette, Wyoming. Autumn鈥檚 speech has become slurred and her cognitive skills slower. She needs help with many tasks, such as writing, showering and dressing, and while she can walk, her balance is off.
Autumn has been turned down for clinical trials because she is too young.
鈥淚t is so frustrating to me,鈥 Tabor said. 鈥淚 would sell my soul to try to get any type [of treatment] to help my daughter.鈥
For patients like Autumn with serious or immediately life-threatening conditions who do not qualify for clinical trials and have exhausted all treatment options, there may be another option: seeking approval from the Food and Drug Administration for , or compassionate use, of experimental therapies.
Definitive numbers are hard to find, but studies from researchers, actions by drugmakers and insights from experts suggest that getting expanded access to unproven therapies for rare diseases is more difficult than for more common illnesses, such as cancer.
Even with experimental treatments on the rise, patients with rare diseases frequently face an unwillingness by drug companies to provide them before clinical studies are completed. Developing drugs for these diseases is an especially fragile process because the patient populations are small and often diverse, having different genetics, symptoms and other characteristics, which makes studying the drugs鈥 effects difficult.
Drugmakers believe offering a drug before studies are finished could impair its development and jeopardize FDA approval.
Companies working on therapies for rare diseases, especially smaller ones, could feel those repercussions acutely, said Lisa Kearns, a researcher in the ethics division of New York University鈥檚 medical school and member of the division鈥檚 working group on compassionate use and preapproval access. 鈥淭here鈥檚 not as much investment in rare diseases, so an [adverse] event could frighten the already limited number of potential investors.鈥
Drugs that were not made available for compassionate use last year until studies were completed include , ; Enspryng, for an ; and , .
A spokesperson for Roche, which makes Evrysdi and Enspryng and is working on a treatment for Huntington鈥檚 disease, said the decision was tied not to the type of disease but to company policy: Roche does not set up expanded access programs for any drugs until results are available from a phase 3 clinical trial. (Those phase 3 studies are typically the last testing done before the company seeks drug approval.)
Another company鈥檚 experimental drug for , an autoimmune disease that leads to skeletal muscle weakness, similarly was not available through until , and no programs have started for a therapy being studied in and , a fatal neurodegenerative disease often referred to as Lou Gehrig鈥檚 disease.
One slight, but notable, deviation: Drugmaker Biogen this year to allow certain ALS patients to receive an experimental drug , after the testing was to be completed but before the results are known.
Dr. Merit Cudkowicz, a neurologist at Massachusetts General Hospital in Boston, has helped patients get therapies through expanded access. Since September 2018, she and colleagues being developed by drug companies, but only about 120 patients have received therapies this way. More than 16,000 people in the United States in 2015 to have ALS and do not qualify for clinical trials because of the progression of their disease or very strict eligibility requirements.
These examples contrast with some drugs for more common problems. , for leukemia, was offered to thousands of patients through expanded access programs before the manufacturer completed the clinical studies that led to FDA approval. , for HIV/AIDS, and , for the most common type of lung cancer, were similarly offered to large numbers of patients even as clinical trials were ongoing.
Last year, Novartis gave more than 7,000 patients worldwide early access to cancer drugs.
Doctors also report that getting experimental drugs for cancer patients is relatively simple. More than 200 physicians around the country were surveyed, and among those who applied for access, said they had secured drugs still being investigated for patients who were not responding to approved therapies.
California researchers found similar trends in a of 23 social media campaigns launched by patients between 2005 and 2015 seeking a variety of experimental treatments. While seven of the 19 patients with cancer received early access to requested drugs, no access was allowed for three patients with rare diseases, although one of those patients was allowed to enroll in a clinical trial.
Companies base their decisions on whether to provide a therapy through expanded access on a number of factors, said Jess Rabourn, CEO of WideTrial, which helps pharmaceutical companies run compassionate use programs. In general, there should be evidence that patients can tolerate the treatment and an expectation that any benefit outweighs the risk, he said.
鈥淭his idea that you have to wait until the research is done is baloney,鈥 he said. 鈥淲e鈥檙e talking about patients who are going to die if they鈥檙e told to wait.鈥
But drugmakers often view it differently, even though evidence suggests that granting early access drug approval.
Kearns explained that companies often wait until phase 3, or after, because they can be 鈥渞elatively鈥 confident of a drug鈥檚 safety and effectiveness. 鈥淭hey don鈥檛 want to harm patients, of course, but they also do not want to threaten the drug鈥檚 eventual regulatory approval with an adverse event in [a] very sick patient population.鈥
Melissa Hogan, who consults on clinical trials for rare diseases and is an , attributes the lack of access to the high cost of therapies and the tightknit nature of the rare disease community, where patients and their families often set up social media groups and exchange ideas and treatment plans. Companies 鈥渒now that if one patient gains access, other patients will know鈥 and ask for access, said Hogan, who has a son with mucopolysaccharidosis type II. That could overwhelm small drugmakers with little manufacturing capacity.
These concerns cause 鈥渕any companies [to] just throw up their hands and take a hard line of no [expanded access] until they reach approval stage,鈥 said Hogan.
The 2018 offers another option for some patients. Unlike expanded access, the law applies only to requests for medicines 鈥 not medical devices 鈥 and does not require approval from the FDA or an , a committee that reviews and monitors people participating in research for their protection. The legislation, however, doesn鈥檛 oblige companies to grant a request.
For Cali Orsulak, expanded access may be her husband鈥檚 only option. He was diagnosed with ALS in 2019 at age 43.
鈥淲e did our best with the skill level we had to search clinical trials all over Canada and the U.S., and then covid hit and it became increasingly difficult,鈥 said Orsulak, explaining that they live in Canada but seek medical care in the United States. 鈥淣ow that my husband has progressed, it鈥檚 even harder to get into clinical trials.鈥
