Ex-AbbVie partner Principia posts encouraging PhII results for its BTK-inhibitor
Months after their breakup with high-profile partner AbbVie, Principia announced positive preliminary results from the second half of a Phase II trial on their lead drug.
The San Francisco biotech announced data from part B of its Phase II open-label trial testing the BTK inhibitor PRN1008 on patients with pemphigus vulgaris, a rare autoimmune disease affecting the skin and mucous membranes. Of 15 enrolled patients, 6 achieved complete responses and 4 remain on the therapy.
Nine of the patients achieved a PDAI score – a 0-to-250 metric for the severity of blistering diseases – of one or zero.
Part B measured the drug over a 24-week period rather than Part A’s 12-week period, and found improvement: The percentage of patients with a complete recovery went from 25% to 40%.
Baird’s Brian Skorney wrote that the results boded well for Principia as it continues with a Phase III study on the same compound that began last year and is still underway. That trial will dose patients for 37 weeks. It aims at 120 enrollees and will be completed at the end of 2021.
“We believe that these results further support the utility of BTK inhibition in pemphigus and should further derisk this program as Principia looks ahead to top-line data from the Phase 3 PEGASUS which are expected in 1H22,” Skorney wrote, adding that the longer dosing period in Phase III may yield more complete remissions.
PRN1008 received FDA orphan drug status for pemphigus vulgaris in 2017. The disease, which causes blistering and ulcers and is spurred by autoantibodies breaking the bond between skin cells, affects 40,000 Americans and 170,000 people worldwide.
As recently as March, AbbVie was working on early-stage research with Principia under a 2017 deal that gave Principia $15 million upfront and $667.5 million in potential milestones. Principia abruptly announced in March that AbbVie had decided to end the collaboration.
“AbbVie has completed an initial evaluation of Principia’s highly selective, orally bioavailable covalent inhibitors of the immunoproteasome and, after an assessment of their biologic profiles relative to AbbVie’s desired disease areas of focus, has determined that there is no longer a strategic fit,” Principia CEO Martin Babler said at the time.
That news came nine days after Principia publicly announced positive results from their Phase II, part A study.
The autoimmune specialist went public last year for an upsized $106 million on the strength of its line of BTK inhibitors. The AbbVie departure leaves it with a main major collaborator in Sanofi. In 2017, the French giant licensed PRN2246, their BTK inhibitor for multiple sclerosis, for $40 million upfront and $765 million in potential milestones.
BTK (Bruton’s tyrosine kinase) inhibitors have long been a major player in hematology but in recent years they have also become a target for autoimmune researchers – a natural leap given they act on an enzyme in B cells, a critical part of the body’s immune system.
Results, though, have been mixed thus far. Merck KGaA announced last month they were moving their BTK, evobrutinib, into Phase III for multiple sclerosis despite mixed Phase IIb results. Last year, Eli Lilly wrote off a BTK for rheumatoid arthritis it had licensed from Korea’s Hanmi, leading to the collapse of a $690 million pact. Celgene similarly saw its auto-immune BTK fizzle in Phase II, while Bristol-Myers Squibb has given few updates on its early-stage BTK program.