IFN-alpha Kinoid, an investigational vaccine by Neovacs, has a favorable safety profile and showed encouraging signs of effectiveness in systemic lupus erythematosus (SLE) patients, according to results from a Phase 2b clinical trial.
While the vaccine candidate failed to meet the trial’s primary objective — an improvement in clinical response — it appeared to ease the burden of corticosteroid treatment, increased the number of patients achieving low disease activity, and was well-tolerated.
These findings will warrant its advancement into a Phase 3 trial, according to Neovacs.
People with lupus are affected by the overproduction of IFN-alpha, an inflammation messenger, or cytokine, that boosts the activation of autoimmune responses against the patient’s own tissues.
Neovacs developed its immunotherapy, or vaccine, candidate to block all 13 subtypes of IFN-alpha, taking advantage of a proprietary technology called Kinoid technology, which stimulates a patient’s immune system to produce its own antibodies against IFN-alpha.
The randomized, double-blind, placebo-controlled Phase 2b trial (NCT02665364) is evaluating IFN-alpha Kinoid for the treatment of patients with moderate to severe lupus. It enrolled 185 patients in 21 countries from Europe, Asia, the U.S, North Africa, and Latin America.
Patients were randomly assigned to get either the vaccine or placebo, given five times through intramuscular injections at days one, seven, and 28, and then at three and six months.
Patients also received standard treatment with antimalarials, immunosuppressants and/or steroids, the latter being progressively reduced until 24 weeks and then left stable until week 36.
The study’s primary goal was to assess the biological and clinical effectiveness nine months (36 weeks) after the first injection of IFN-alpha Kinoid. Secondary objectives included other disease activity measures and safety.
After 36 weeks, there was a significant decrease in the expression of IFN-dependent genes, a readout of IFN-alpha activity, in patients treated with the vaccine versus those treated with placebo.
However, clinical response, measured by the BILAG Based Combined Lupus Assessment (BICLA) score, one of the primary outcome measures, failed to significantly change with treatment.
But patients treated with IFN-alpha Kinoid did show signs of clinical improvement. They were able to more effectively taper their daily corticosteroid dose, the use of which can cause organ damage in these patients.
More patients who received IFN-alpha Kinoid (54.4%) were able to reduce their steroid use to 5 mg a day or less, compared with those treated with placebo (39%).
“It suggests that one must take into account the reduction of steroid therapy, an important goal of treatment,” Frédéric Houssiau, MD, PhD, from the rheumatology department at Saint-Luc Clinical Universities in Belgium and scientific chairman of the study, said in a press release.
Also in favor of IFN-alpha Kinoid, significantly more patients on the therapy achieved low disease activity (52.9%) — measured by the Lupus Low Disease Activity State (LLDAS) score — than the placebo group (29.8%).
Importantly, treatment with IFN-alpha Kinoid was well-tolerated, and did not result in more adverse events than placebo.
Following a primary period of evaluation, patients will enter a five-year follow-up period to assess the safety and the long-term biological and clinical effectiveness of the vaccine.
“These results of clinical efficacy, in particular on two reference indices (SRI-4 with steroid reduction to less than or equal to 5 mg/day and LLDAS) which have been validated by international health authorities or medical community, authorise the further clinical development with these scores into phase III,” said Thérèse Croughs, MD, chief medical officer of Neovacs.
Neovacs plans to present the full results at a future scientific conference.
IFN-alpha Kinoid was granted fast track designation by the U.S. Food and Drug Administration in December 2016.