Barzolvolimab

Celldex said Tuesday that its investigational drug barzolvolimab met the primary and all key secondary endpoints of a pair of Phase III studies in chronic spontaneous urticaria (CSU), setting up an FDA filing for the anti-KIT monoclonal antibody next year. Despite the seemingly positive news, shares in the company fell around 30% in premarket trading, before paring some of its losses once trading started.The stock dip may have been the result of investor concerns over barzolvolimab's safety profile, with two "probable" cases of grade 4 anaphylaxis seen in patients given the drug in the trials. Another grade 4 anaphylaxis event was seen in a participant on barzolvolimab, although Celldex noted that this occurred after the placebo dose.In announcing the data, the company said barzolvolimab was "well tolerated with a favourable safety profile through 24 weeks."The two trials — EMBARQ-CSU1 and EMBARQ-CSU2 — enrolled a total of 1939 patients with CSU whose symptoms are inadequately controlled by H1-antihistamines. Participants were randomised to receive a loading dose of barzolvolimab, followed by treatment every four weeks with one of two doses of the drug, or placebo for the 24-week treatment period.The primary endpoint of the studies evaluated clinical effect at reducing urticaria activity at week 12, as assessed by the weekly urticaria activity score (UAS7), with key secondary goals including the proportion of patients with a complete response, as measured by a UAS7 score of zero.Top-line results showed that in both studies, the mean change from baseline in UAS7 was -20.2 for the 150-mg dose, while for the 300-mg dose it was -20.5 and -19.7 in EMBARQ-CSU1 and EMBARQ-CSU2, respectively. Celldex said these represent a clinically meaningful and highly statistically significant improvement versus placebo, which was associated with mean UAS7 changes of -10.7 and -11.4 in the two trials, respectively.Complete responses at week 12 occurred at rates of up to 45.7% for the 150-mg dose arm and up to 44% at the 300-mg dose, versus up to 12.6% for placebo. At week 24, these rose to up to 54% for the 150mg dose, 48.4% for the 300-mg dose and 17.6% for placebo."Barzolvolimab continued to show unprecedented complete response rates across the overall studies," Chief Medical Officer Diane Young said, calling the drug a potential "a transformational therapy" for people with CSU.Celldex has long touted barzolvolimab as a "pipeline in a product," with a Phase III study under way in cold urticaria and symptomatic dermographism, as well as a mid-stage trial in atopic dermatitis. However, the drug has also suffered some missteps, with Phase II setbacks in both prurigo nodularis and eosinophilic oesophagitis.

Dive Brief:Celldex shares sank 13% in early trading Tuesday as investors focused on safety concerns for a medicine that the drugmaker says can transform treatment of a debilitating skin disease.The company on Tuesday released results from two successful Phase 3 studies of the drug, barzolvolimab, in patients with a condition called chronic spontaneous urticaria that causes hives and severe itching, burning or swelling. But some investors keyed in on two cases of anaphylaxis in one of the barzolvolimab-dosed groups.Celldex downplayed concerns about the drugs safety, with CEO Anthony Marucci telling analysts on a conference call that the incidence was extremely low among about 2,400 patients that have been treated overall. In its press release, the company said barzolvolimab was well-tolerated and displayed a favorable safety profile.Dive Insight:Barzolvolimab is the centerpiece of Celldexs transformation from an oncology company to one focused on immunology. After several research failures in cancer, Celldex turned to barzolvolimab as a new way to treat conditions such as urticaria by driving down counts of mast cells implicated in hives. Early tests showed it might be faster-acting, more potent and more durable than current therapies.At least one analyst said Celldexs theory has now been proven. Wed pound the table that Celldexs efficacy looks to be the best Phase 3 data set weve seen across all pivotal studies, Cantor Fitzgerald analyst Kristen Kluska wrote in a note to clients. Safety, meanwhile, appears favorable to other biologics that currently produce billions of dollars in revenue, she wrote.While its hard to predict exactly how the Food and Drug Administration will act on the anaphylaxis cases, Stifel analyst Alex Thompson wrote in a note to clients that hes optimistic. He noted that top medicines including Dupixent have warnings about anaphylaxis and said he still expects meaningful sales for barzolvolimab even if it gets a boxed warning and becomes relegated to last-line usage.Kluska, meanwhile, forecasts that peak sales of the medicine will reach $4.8 billion. Celldex plans to develop the drug for other uses as well and is already testing it in three different indications other than chronic spontaneous urticaria.In the two new studies, researchers enrolled almost 2,000 patients who didnt respond well enough to typical antihistamine therapies. In the initial phase, participants were split into three groups, randomly assigned to either get a placebo or one of two dosing regimens of barzolvolimab. After all the patients had been treated for 24 weeks, researchers performed the analysis released Tuesday. The study is designed to follow patients for a year.Celldex said the results were unparalleled for patients with chronic spontaneous urticaria, showing a significant reduction in urticaria activity the studys main objective as well as success in key secondary endpoints. In the two groups that received barzolvolimab, about half of patients had a complete response total absence of itch and hives after 24 weeks, compared with between 15% and 18% in the placebo group.Still, analysts said they are looking closely at the drugs safety. One concern that has persisted about barzolvolimab is whether the drug might reduce levels of neutrophils too much, potentially leaving patients vulnerable to infections. Other than neutropenia, the most common side effects are changes in hair color and skin pigmentation.The anaphylaxis cases were detailed in a slide listing adverse events. One occurred after a dose of placebo, while two occurred in one of the barzolvolimab-dosed groups. Physicians may just opt to give the first dose of the medicine in their clinics to monitor for potential issues, Kluska said.Celldex said it plans to file for FDA approval of barzolvolimab next year. '