A phase 2 study of Celldex’s barzolvolimab in a chronic skin disease has missed its primary endpoint, driving the biotech to end development in the indication and raising doubts about an upcoming eczema readout.
Barzolvolimab, an anti-KIT antibody, could deplete mast cells to treat inflammatory conditions. Celldex chose chronic spontaneous urticaria (CSU) and cold urticaria—a form of chronic inducible urticaria (CIndU)—as its lead indications. While running phase 3 trials in those settings, the biotech has worked to expand into the skin disorders atopic dermatitis (AD) and prurigo nodularis (PN) via midstage trials.
Celldex reported the failure of the phase 2 PN trial after the market closed Tuesday. The study missed its primary endpoint, which looked for improvements on an itch scale at Week 12. Barzolvolimab also failed to move the needle on secondary endpoints. The failures occurred despite Celldex reporting “profound systemic mast cell depletion.”
The biotech ran the study on the strength of a phase 1b trial that linked barzolvolimab to improvements in itch compared to placebo. Celldex changed the administration route for the phase 2, switching from intravenous to subcutaneous delivery.
The switch might have contributed to the failure to replicate the phase 1b data, TD Cowen analysts said in a note to investors. But the analysts suggested, “the more likely conclusion is that mast cells are simply not a pathogenic driver for PN.”
That conclusion has implications for the phase 2 readout in AD, which is due in the fourth quarter. The PN failure “somewhat weakens the argument” for barzolvolimab in AD because “both indications share components of pruritic disease which were hypothesized to be mast-cell driven,” the analysts added.
On a conference call with investors to discuss the data Tuesday, Tibor Keler, Ph.D., chief scientific officer at Celldex, acknowledged that the overlap between the indications was part of the rationale for running an AD trial after seeing phase 1b data in PN. However, mast cells affect other parts of the inflammatory process in AD, Keler said, and Celldex plans to complete the atopic dermatitis study.
TD Cowen analysts said in a May note that the PN and AD trials “ought to be successful in our view.” But after the phase 2 flop, the analysts emphasized that “investor expectations for AD have always been very low.” PN was “largely off the radar for most investors,” the analysts said. Celldex shares fell 7% to about $33 in premarket trading Wednesday after the phase 2 failure.
The PN results are disappointing, the analysts added, but “our thesis for Celldex remains unchanged, as we viewed PN to be upside to the core indications of CSU and CIndU, which continue to show impressive efficacy and tolerable long-term safety.”
Barzolvolimab showed a favorable safety and tolerability profile in the phase 2 PN trial, Celldex said. An investigator reported a case of aseptic meningitis as a serious, treatment-related adverse event, but Celldex strongly disagreed with the diagnosis and relatedness.
“We think that the clinical picture of the chest pain, which really went on for weeks, as well as the modest increase in cells in the CSF, really indicate some sort of neuroinflammatory process, most likely due to a virus,” Diane Young, M.D., chief medical officer at Celldex, said on the call. “They did not have any neutropenia.”
Celldex doesn’t believe there is any read-through from the PN trial to the phase 3 studies, Young said. “We have no concerns about efficacy,” the CMO said, adding that “we feel, if anything, that in this study the safety profile really looked great, even with using the higher dose, and we feel that that reads through well to all of our indications.”