Ablynx and Protagonist Therapeutics today acknowledged mid-stage trial failures, with both companies saying they are evaluating the future of the pipeline candidates that generated the disappointing clinical results.
Ablynx—which is being acquired by Sanofi for €3.9 billion ($4.8 billion)—disclosed that its systemic lupus erythematosus (SLE) candidate vobarilizumab missed its primary endpoint of dose response in the Phase II STEADY SLE dose-ranging study based on the modified BILAG-based combined lupus assessment (mBICLA) at week 24.
The failure may trigger a second rejection by AbbVie of plans to license vobarilizumab in SLE. The first rejection of the drug came in 2016 when AbbVie opted against licensing the drug candidate in rheumatoid arthritis after it generated mixed Phase IIb results. Three years earlier, AbbVie paid $175 million upfront for licensing rights to vobarilizumab, then called ALX-0061, as part of a broader inflammatory disease collaboration that could have generated up to $840 million for Ablynx.
“AbbVie will review the complete data set when available from the Phase II STEADY SLE study to determine whether to exercise its option to license vobarilizumab,” Ablynx stated in a company announcement. “Should AbbVie exercise the option, it would trigger a payment to Ablynx. If the option is not exercised, Ablynx's agreement with AbbVie would terminate.”
STEADY SLE was initiated in August 2015 and enrolled 312 patients with moderate to severe, active seropositive SLE across five treatment arms—four dose regimens of vobarilizumab and placebo. Ablynx said two deaths were reported in the vobarilizumab group, which saw treatment-emergent adverse events leading to discontinuation reported in 12.4% of all treated patients, versus 6.5% in the placebo group.
Ablynx highlighted favorable safety results through week 58, showing that treatment-related serious adverse events were reported in 2.0% of all vobarilizumab-treated patients versus 6.5% in the placebo group.
“We are disappointed that vobarilizumab didn't show a dose response in the analysis of the study's primary endpoint; however, vobarilizumab was well tolerated in all tested dose groups, confirming its favorable safety profile,” Ablynx CMO Robert K. Zeldin, M.D., stated. “We will continue to analyze the full dataset and thank the study participants and their families as well as the investigators and staff who contributed to this study.”
Vobarilizumab targets the interleukin-6 (IL-6) pathway via its IL-6 receptor (IL-6R); the drug contains an anti-IL-6R Nanobody® linked to an anti-human serum albumin (HSA) Nanobody, designed to increase the in vivo serum half-life.
Nanobodies are therapeutic proteins that are based on single-domain antibody fragments that contain the structural and functional properties of naturally occurring heavy-chain-only antibodies. Ablynx says its proprietary Nanobody platform allows for rapid generation and large-scale production of novel biological therapeutics that have potential in a wide range of human diseases.
PTG-100 Fails PROPEL Study
Protagonist said it would assess the future of its development program for the ulcerative colitis (UC) candidate PTG-100 after discontinuing the Phase IIb PROPEL study assessing the drug in patients with moderate to severe UC.
The decision to end the trial followed an assessment by the study’s independent Data Monitoring Committee (DMC) that the trial was futile based on an analysis of the primary endpoint of clinical remission.
The assessment came after the close of the market on Friday, and came during a planned interim analysis of unblinded efficacy and safety data from the first 65 patients from the ongoing 240-patient trial who had completed the 12-week treatment with PTG-100, Protagonist said, adding that no safety concerns were noted.
PROPEL was a global, randomized, double-blind, placebo-controlled, two-stage, adaptive clinical trial designed to assess the safety, efficacy, and dose optimization of three doses (150 mg, 300 mg, or 900 mg) of PTG-100 compared to placebo for 12 weeks. The study’s primary efficacy endpoint was the proportion of patients who achieved clinical remission as defined by rectal bleeding, stool frequency, and endoscopic subscores of the Mayo score.
Pending further review of PROPEL results, Protagonist added, the company is notifying trial investigators to discontinue randomization of potential participants and further treatment of patients currently in the study. Protagonist added that it will also hold off on deciding whether to launch a Phase II/III clinical trial of PTG-100 in chronic pouchitis until after its full review of interim data from PRPOPEL.
“We are very disappointed with this futility-based outcome, which was also accompanied by an unexpectedly high placebo rate,” Protagonist president and CEO Dinesh V. Patel, Ph.D., said in a statement. “We will conduct an extensive review of the complete dataset on the totality of patients enrolled in the trial before making any further decisions about the future development of PTG-100.”
TG-100 is an investigational oral gastrointestinal (GI)-restricted alpha-4-beta-7 (α4β7) integrin-specific antagonist peptide product candidate. Protagonist has reasoned that α4β7 integrin is one of the most GI-specific biological targets for inflammatory bowel disease due to its binding to