RARE Daily

Akari Reports Positive Results from Clinical Trial in Bullous Pemphigoid Patients

May 1, 2020

Rare Daily Staff

Akari Therapeutics reported that it achieved the primary and secondary endpoints for its experimental therapeutic nomacopan in a phase 2 trial for the treatment of patients with the rare autoimmune condition bullous pemphigoid.

Bulous pemphigoid (BP) causes severe blistering skin disease with no approved treatments in the United States and Europe. It is most common in the elderly, and is primarily treated with steroids and immunosuppressants for six months or more, which can have deleterious side effects and an approximately three-fold increase in mortality.

There is evidence that both terminal complement activation (via complement component C5) and the lipid mediator leukotriene B4 (LTB4) have a central role in driving the disease. This underlies the rationale for treatment with nomacopan, an inhibitor of both C5 and LTB4 and a range of downstream cytokines that was derived from tick saliva.

“The role of both the leukotriene and complement pathways has been well documented in BP and the rapid clinical response and good safety profile seen in this phase 2 study was extremely positive given nomacopan’s unique bi functional inhibition of both C5 and LTB4,” said Clive Richardson, CEO of Akari Therapeutics. “Our next steps are to work closely with U.S. and European regulators in order to secure a clear path forward to a pivotal trial for this severe orphan disease which has significant unmet clinical need and is a potential gateway to other dermatological conditions.”

The fully recruited phase 2 trial of nomacopan for treatment of mild-to-moderate BP was a six-week open-label single-arm study evaluating safety and efficacy in 9 patients (7 with moderate severity, 2 mild). Patients entering the trial were at their choice permitted to use a low dose of the corticosteroid mometasone topically to lesions for up to three weeks as this was the first study of nomacopan in BP patients.

The trial achieved the main efficacy endpoints, which were clinically significant improvements in the Bullous Pemphigoid Disease Area Index (BPDAI) a measure of the area of skin affected by inflammatory skin lesions. Seven out of nine patients showed a decrease by 4 or more points (deemed a minimal clinically important difference) in the BPDAI activity score between baseline and six weeks of treatment, while two patients, both with relapsing disease on admittance to the trial, were non-responders.

One patient experienced a flare in their disease after day 28, which is common in BP where patients are typically treated for six months or more with steroids to enable disease control. The two non-responders showed worsening disease with an increase in their BPDAI score. The combined mean decline in the BPDAI index for all nine patients was approximately 40 percent at day 42.

Of the seven responders, three showed an 80 percent plus reduction in BPDAI score and three an approximately 40 percent reduction in BPDAI score within six weeks of starting nomacopan. For the responders, the response on nomacopan was rapid and is similar to what is seen with patients treated on potent oral steroids which is standard of care in the U.S. and parts of Europe for moderate to severe patients. Similarly, under typical standard of care around 20 percent of BP patients are considered non-responders.

Nomacopan, dosed daily by subcutaneous injection, was well tolerated in this frail BP patient population with multiple comorbidities. The primary endpoint was the proportion of participants reporting grade 3, 4 and 5 adverse events, which are related/possibly related to nomacopan. None of the nine patients reported any such treatment related adverse events. Nomacopan was well tolerated with no drug-related serious adverse events observed to date.

Nomacopan has been granted orphan drug designation by the U.S. Food and Drug Administration for the treatment of BP. Akari expects to meet with the FDA and the European Medicines Agency to discuss pivotal trial design in third quarter 2020. The company is also testing nomacopan for the treatment of atopic keratoconjunctivitis and thrombotic microangiopathy.

Photo: Clive Richardson, CEO of Akari Therapeutics

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