Rare Daily Staff

Regeneron Pharmaceuticals reported topline data from the pozelimab phase 2 clinical study in paroxysmal nocturnal hemoglobinuria, validating the weekly 800 mg subcutaneous dosing regimen, following an initial intravenous loading dose.

The results from the initial six-patent cohort show pozelimab reduced the abnormal destruction of red blood cells, otherwise known as “hemolysis,” with the patients achieving normal levels of a blood biomarker of elevated hemolysis called lactate dehydrogenase (LDH).

Paroxysmal nocturnal hemoglobinuria (PNH) is an ultra-rare, chronic, life-threatening disease where genetic mutations cause hemolysis, which results in a range of symptoms including fatigue, shortness of breath and blood clots. It can occur at any age, but is usually diagnosed in young adulthood. It is caused by acquired mutations in the PIGA gene and is not passed down to children. Even with existing therapies, which require regular intravenous infusions administered at infusion centers or during a home visit by a health professional, approximately 50 percent of newly-treated patients do not achieve normal LDH levels.

“In our view, any new medicine for PNH must deliver real change for patients, such as more patients achieving normal LDH levels, or a reduced treatment burden that potentially allows for at-home self-administration,” said George Yancopoulos, president and chief scientific officer at Regeneron. “We are encouraged by these early pozelimab results, with patients achieving normal levels of LDH by week 8 using the subcutaneous dosing regimen. We look forward to speaking with regulators about the next phase of our program for these patients.”

Pozelimab is an experimental, fully-human monoclonal antibody designed to block complement factor C5 and prevent the destruction of red blood cells (hemolysis) that cause the symptoms of PNH and other diseases mediated by complement pathway activity. It is an IgG4 antibody that binds with high affinity to wild-type and variant human C5 and blocks its activity.

All six patients in the initial treatment cohort treated with an initial loading dose followed  by weekly subcutaneous injections of pozelimab experienced rapid and sustained reductions in LDH up to week eight. No adverse events were serious or led to discontinuation. At the cut-off date of the analyses, treatment-related adverse events were reported in three patients (50%), including headache (n=2), injection site reaction (n=1) and nausea (n=1). One patient received a blood transfusion on day 50 due to underlying bone marrow dysfunction.

The second part of the ongoing open-label, single-arm study is enrolling approximately 30 patients with active symptomatic PNH who are naïve to complement inhibitors or who have not received treatment with a complement inhibitor within six months prior to entering the trial. It will focus on further evaluating efficacy and safety in a larger PNH population.

Data from the phase 2 trial will be presented at an upcoming medical meeting. Regeneron says the trial could potentially provide pivotal data supporting approval for this orphan disease indication and plans for a phase 3 trial are underway.

Photo: George Yancopoulos, president and chief scientific officer at Regeneron

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