Newly listed biotech Principia Biopharma has started a phase 3 program for its lead BTK inhibitor in the rare autoimmune disease pemphigus after hitting the target in a midstage trial.
In the phase 2 study in 27 patients with pemphigus, PRN1008 was able to achieve control of disease activity in more than 50% of subjects within four weeks of starting treatment, raising the possibility that it could be used to wean patients off harmful doses of corticosteroid drugs—the most commonly used therapy. It also showed sustained clinical efficacy at 12 weeks of therapy, a secondary endpoint.
Buoyed by the early efficacy signal, Principia said it is already moving ahead with a phase 3 trial, called PEGASUS, that will enrol around 120 patients who are either newly diagnosed with pemphigus or relapsing with chronic disease and look at 36 weeks of treatment with the drug. The main endpoint is complete remission when the drug is used with a very low dose of steroid.
Meanwhile, the biotech is also extending the phase 2 study to increase the active treatment period from 12 to 24 weeks and should have data from that available in the second half of 2019.
Pemphigus is a group of diseases caused by an antibody reaction to healthy tissues that results in painful and debilitating blisters in the skin and mucous membranes. First-line treatment is generally uses steroids with immunosuppressants such as azathioprine, mycophenolate and cyclophosphamide held in reserve to avoid steroid-related side effects. These drugs are also hard to tolerate, however, so there’s a real need for new steroid-sparing options.
Analyst Geoffrey Porges at Leerink said in a research note a few weeks ago that he thinks PRN1008 has a 65% chance of approval for pemphigus and could eventually make $550 million in sales, providing it also gets approved in followup indication immune thrombocytopenic purpura.
Blocking BTK with PRN1008 down-regulates certain cellular processes that are activated in autoimmune and inflammatory diseases, said Principia, although the BTK inhibitor class is best known as the target of Janssen’s Imbruvica, approved back in 2013 for patients with blood cancers.
Meanwhile, other companies trying to bring forward new therapies for pemphigus include Argenx, which is developing its efgartigimod (ARGX-113) candidate for a form of the disease known as pemphigus vulgaris in phase 2, and Syntimmune—now snapped up by Alexion—which reported positive data in a phase 1b trial of its anti-immunoglobulin drug SYNT001 in May.
South San Francisco-based Principia licensed a different BTK inhibitor, PRN2246, to Sanofi in November. This one is in development for multiple sclerosis as it can cross the blood-brain barrier, going up against a similar program at Merck KGaA which cleared a phase 2 study earlier this year. Analysts at Baird said recently that candidate could have blockbuster sales potential.