An experimental drug from Celldex Therapeutics is showing early promise treating a debilitating skin condition, results that are giving the 16-year-old biotech a chance for a comeback after a high-profile clinical trial failure.
A single infusion of Celldex's drug helped prevent the return of severe, burning skin hives in 18 of 19 people enrolled in an early-stage study. No serious side effects were reported beyond a previously disclosed infusion reaction that researchers concluded wasn't tied to treatment.
The results, set to be presented at a medical meeting in Europe this weekend, have limitations. The small study is designed to assess safety, and did not randomize participants to receive placebo as a control. It's unclear whether subsequent doses of the drug will be as effective as the first or whether lowering counts of a type of immune cell known as mast cells, as Celldex's drug does, will cause problems over time.
Nonetheless, the findings are significant, said Marcus Maurer, the study's lead investigator and a professor of dermatology and allergy at Charité-Universitätsmedizin in Berlin. According to Maurer, the study proves for the first time that chronic hives are caused by mast cells and that depleting them may help.
"I've been waiting for this for 20 years," said Maurer, who treats people with many mast cell-driven diseases, among them chronic urticaria, as the condition is called. "It's just great to see what happens to these patients."
Celldex has been waiting a long time for good news, too, after its fortunes faded in the wake of clinical trial failures, most notably of a closely watched brain cancer vaccine called Rintega.
"It was tough, to be honest with you," said Celldex CEO Anthony Marucci. "It's never easy to go through these setbacks."
Friday's results, then, are a hopeful sign and a much-needed opportunity in a treatment space Marucci says Celldex is well-suited to pursuing.
Chronic urticarias are a group of inflammatory skin conditions characterized by hives that form on the arms, legs or elsewhere and can cause severe itching, burning or swelling. The "inducible" form occurs in response to a trigger, such as cold or warm temperature, scratching or even sunlight. But urticarias can arise spontaneously as well and threaten to suddenly return for weeks or even years. Millions of people in the U.S. are estimated to be affected.
The impact can be devastating, Maurer said. Patients might stay indoors for months to keep away from the winter cold, or stop exercising so their internal temperature won't rise. They'll sleep during the day to avoid sunlight, or tailor their jobs to avoid triggering the hives. Though treatments such as antihistamines and the biologic drug Xolair are available, they don't work for a majority of patients. Even if they do, benefits can take weeks to materialize.
"We are in a real pickle here," Maurer said. "Patients desperately need something to protect them."
Celldex executives hope their drug will be able to protect patients with a few doses per year. Volunteers in the Phase 1b trial had forms of chronic inducible urticaria triggered by either cold or scratching. They were periodically tested against those triggers and, in March, initial results showed an 80% complete response rate, meaning patients no longer developed hives in those circumstances.
New results disclosed Friday show all but one, or 95%, of patients completely responded, with responses lasting a median of either 57 or 77 days depending on the type of urticaria.
The effects kicked in quickly, said Marucci. "What we're most excited about is the speed of response," he said. "That's a clear differentiator."
Side effects were generally mild, like changes to hair color and the ability to taste salt. A single severe infusion reaction reported in March was related to pre-existing neurological problems, not anaphylaxis as some had feared, Maurer said. Trial participants considered the hair or taste changes "more of a nuisance or peculiarity," he added.
Celldex will test multiple doses in a Phase 2 study next year and could start testing of an injectable version of the drug before then.
The initial findings suggest Celldex's drug could treat several types of urticarias or other diseases linked to mast cells, said Margot Heath-Chiozzi, its head of regulatory affairs. A chronic rash called prurigo nodularis is up next.
Celldex has had success before, only to see once-promising drugs fall short in later testing. The company was spun out of the research labs of Medarex, the original developer of the cancer immunotherapies now known as Opdivo and Yervoy and sold by Bristol Myers Squibb. Celldex later acquired a few small biotechs and their research.
The most prominent of the projects to emerge was Rintega, a vaccine for a particularly deadly form of brain cancer. Celldex spent years developing it, and got further than most others in the industry that have worked on cancer vaccines. Rintega looked promising enough at one point that executives discussed the possibility of seeking accelerated approval in the U.S. But in 2016, Rintega failed a Phase 3 trial in a major disappointment.
Celldex continued to develop other cancer treatments, yet shares plunged to $2 each after a breast cancer drug failed a Phase 2 trial in 2018. The company reworked its pipeline, cut jobs and changed its strategy.
Celldex had something to fall back on, though. The company had previously bought Kolltan Pharmaceuticals, which was working on drugs meant to overcome treatment resistance in cancer. Celldex originally viewed its lead program as a potential therapy for a type of gastrointestinal tumor, but after testing failed, the company tweaked the drug so it might be useful outside of oncology.
That led to urticaria, which has given Celldex a chance at reinvention. Shares have climbed steadily higher for months and are now worth about $32 apiece, roughly what they traded at before the breast cancer drug failed.
"I know our background was oncology for the most part and we still have an oncology portfolio," Marucci said. "But first and foremost, the team is our immunologists, and they'll take us wherever the science goes."