Orphan Drug Designation Granted to Pemphigus Treatment, SYNT001


The FDA has granted an orphan drug designation to Syntimmune Inc.’s SYNT001 for the treatment of pemphigus.

The US Food and Drug Administration (FDA) has granted an orphan drug designation to Syntimmune Inc.’s SYNT001 for the treatment of pemphigus.

“This is an important milestone for the SYNT001 clinical development program and highlights the high unmet medical need for new therapies with the potential to improve the lives of pemphigus patients and their families,” said Jean-Paul Kress, MD, president and CEO of Syntimmune, in a recent statement. “We believe there is significant potential for SYNT001 in pemphigus and other autoimmune diseases and look forward to providing additional clinical data.”

Positive preliminary results from a phase 1b proof-of-concept trial of SYNT001 in patients with pemphigus served as the basis for the approval. In the first cohort, SYNT001 was observed to be well tolerated and induced a rapid reduction in IgG and circulating immune complex levels. In addition, as measured by Pemphigus Disease Area Index (PDAI) score, SYNT001 induced clinical improvement, with clinical effect persisting beyond the treatment period.

The ongoing, multi-center, open-label study is evaluating SYNT001 in 3 successive dosing cohorts, each to be treated with 5 weekly intravenous doses of SYNT001, with dose escalation between cohorts up to a maximum of 45 mg/kg.

The primary endpoint of the trial is safety and tolerability, while secondary endpoints include PDAI, total IgG, CIC and serum anti-desmoglein IgG (anti-DSG1 and anti-DSG3) levels.

According to the trial’s preliminary results, mean total IgG levels were reduced by 59% (day 30), mean circulating immune complex (CIC) levels were reduced by 50% (day 33), mean anti-DSG1 levels were reduced by 22% (day 14), and mean anti-DSG3 levels were reduced by 24% (day 33).

“We believe that effective reduction in PDAI scores at this lowest dose indicates the potential for a greater magnitude and duration of response at higher doses. In individual patients, we saw reductions of up to 67% in total IgG, 71% in CIC, 65% in anti-DSG1 and 61% in anti-DSG3,” Jean-Paul Kress, MD, president and CEO of Syntimmune, commented in a recent statement.

“These results strengthen our conviction that reducing pathogenic autoantibodies and blocking key inflammatory functions of FcRn may offer an innovative approach to treat pemphigus and could give rise to therapeutic benefits in a wide range of autoimmune diseases that are similarly mediated,” he added.

The preliminary data from the phase 1b trial included 7 patients—6 with pemphigus vulgaris (PV)—and 1 with pemphigus foliaceus (PF) who were in the first cohort and had been administered 5 weekly infusions of SYNT001, 10 mg/kg, and are in varying stages of follow-up. These results were reported at the International Investigative Dermatology meeting earlier this year.

Optimized to inhibit FcRn binding to IgG at both neutral and acidic pH, SYNT001 is an investigational humanized IgG4 monoclonal antibody.

Pemphigus is a rare, autoimmune skin disease in which water blisters develop on the skin.

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