NEW YORK – The first Sjögren's disease patient has received an autologous cell therapy developed at the University of Wisconsin School of Medicine and Public Health to treat a symptom of the chronic autoimmune disorder.
In Sjögren's disease, the immune system attacks certain glands in the body that produce moisture, resulting in a variety of symptoms linked with chronic dryness, most commonly in the eyes and mouth. That includes severe dry mouth, known as xerostomia, which can limit a patient's ability to eat and lead to health issues such as tooth decay.
There aren't any disease-modifying drugs approved by the US Food and Drug Administration for Sjögren's disease, and standard care tends only to address its symptoms. For dry mouth, patients might take oral medications designed to increase saliva production or take other steps to encourage saliva production, like using special lozenges or chewing sugar-free gum.
"The medications available do nothing to remodel or address the underlying issue," said Sara McCoy, an assistant professor at the UW School of Medicine and Public Health and a rheumatologist at UW Health, where she runs a Sjögren's disease clinic. She added that these drugs have a high risk of side effects, including severe sweating and gastrointestinal upset.
The cell therapy, developed through the UW Program for Advanced Cell Therapy (PACT), involves activating a patient's own bone marrow-derived mesenchymal stromal cells by stimulating them with interferon-gamma, which enhances their ability to suppress immune response and promotes tissue repair.
The idea is that, when injected into a patient's salivary glands, these cells will improve the function of salivary gland tissue.
PACT was launched by UW Health and the UW School of Medicine and Public Health in 2016 to advance experimental cell therapies. The program manufactures cell therapies, supports researchers in preparing investigational new drug applications to submit to regulators, and conducts preclinical studies and first-in-human clinical trials to de-risk these potential treatments.
The clinical trial in Sjögren's disease builds off previous work at PACT testing the same cell therapy in patients with radiotherapy-induced xerostomia, said Jacques Galipeau, director of PACT and associate dean for therapeutics development at the UW School of Medicine and Public Health. He joined the university in 2016 to launch PACT.
In a pilot study, six patients who had developed xerostomia after radiation therapy for head and neck cancer received the cell therapy, and about half of those patients improved and produced more saliva after the injection, according to results published in Cytotherapy. Investigators are continuing to study the cell therapy in this patient population within a Phase I trial.
After observing how well the cell therapy had worked in radiation-induced dry mouth, Galipeau approached McCoy about pursuing a similar clinical trial in Sjögren's disease.
"The common denominator for both of these use cases is that it's a really serious medical problem for the patients and there are no FDA-approved treatments," Galipeau said. "We have clinical domain experts here who can recruit patients and know how to assess them and assess response."
If a cell therapy at PACT has positive results and seems worth continuing to study, Galipeau expects to license it, either to an outside company or one that the program launches. He added that, over the next year, PACT is working to launch a startup that could advance therapeutic candidates into late-stage clinical trials and, hopefully, through regulatory approval and commercialization.
The first Sjögren's disease patient to receive the cell therapy in the Phase 0 trial, who was administered the novel treatment in January, had suffered from xerostomia, alongside other symptoms like dry eye, joint pain, and rapid weight loss. So far, she has reported that the cell therapy has helped her feel less dry mouth, though it's still early, McCoy said.
The inclusion criteria for the clinical trial are fairly broad, according to McCoy, but for her own patients she said she's mainly recruiting those who aren't eligible for other studies.
Since the cell therapy is autologous, that leaves open the possibility for patients to receive additional injections, if needed, she noted.
McCoy is applying for a grant to fund a Phase I trial at UW Health to assess safety and preliminary efficacy of the cell therapy at escalating doses, which she hopes could launch around the end of the year. For that study, investigators expect to enroll additional adults with dry mouth and either Sjögren's disease or graft-versus-host disease, which can also lead to xerostomia, who then will be monitored for two years.
In the Phase I trial, McCoy said investigators ideally would like to inject the cell therapy twice, into the two salivary glands below the chin, but need more data before the FDA will allow it.
Investigators plan to enroll five more patients into the ongoing Phase 0 trial, which is also for patients with Sjögren's disease or graft-versus-host disease. The initial six patients in the Phase 0 trial will receive injections to just one gland, which will provide that safety data.
If investigators observe positive results from the Phase 0 trial and continued good findings in the Phase I trial, McCoy said she expects to "move really quickly" to advance toward a multicenter Phase II trial to evaluate the cell therapy's efficacy. "We'd move pretty quickly in getting this therapy expanded to additional patients," McCoy said.