PITTSBURGH--(BUSINESS WIRE)--Knopp Biosciences LLC today announced detailed results of its positive Phase 2 dose-ranging EXHALE trial of the novel oral eosinophil-lowering drug dexpramipexole in patients with moderate-to-severe asthma. The data were presented in a virtual poster session at the ATS 2021 International Conference.
The EXHALE trial was a randomized, double-blind, placebo-controlled study of dexpramipexole in patients with moderate-to-severe asthma and blood absolute eosinophil count (AEC) ≥300/µL. Dexpramipexole study drug at oral doses of 75 mg/day, 150 mg/day, or 300 mg/day was added to standard of care. The primary endpoint was change in AEC from Baseline to Week 12 compared to placebo. Eosinophils, a type of white-blood cell, are validated as a therapeutic target in asthma as evidenced by the regulatory approval of multiple eosinophil-lowering biologics. The EXHALE trial enrolled 103 patients from 21 U.S. study centers. The majority of patients had severe asthma as classified by the Global Initiative for Asthma. Minority populations represented 23% of the patients enrolled.
Following are highlights of the ATS 2021 poster presentation by Calman Prussin, M.D., Knopp’s Vice President of Clinical and Translational Medicine:
- Treatment with dexpramipexole resulted in significant reductions in AEC from Baseline to Week 12 at all doses tested (75 mg/day, p=0.019; 150 mg/day, p=0.001, and 300 mg/day, p<0.001). Dexpramipexole demonstrated a dose-dependent effect on eosinophil lowering that was significant by log-linear testing (p<0.001).
- Patients receiving dexpramipexole 300 mg/day achieved an 80% reduction in their AEC from Baseline to Week 12 (p<0.001).
- While the study was not powered to assess lung function, patients receiving dexpramipexole 300 mg/day had an increase in placebo-corrected pre-bronchodilator peak forced expiratory volume in one second (FEV1) of 182 mL at Week 12 (p=0.099). Notably, this FEV1 improvement was maintained through the Week 16/18 visit (∆FEV1 225 mL, p=0.036), despite patients having been off drug for 4-6 weeks.
- A post-hoc analysis of all dexpramipexole doses across all study visits demonstrated a placebo-corrected improvement in prebronchodilator FEV1 of 172 mL (p=0.015).
Dexpramipexole was well tolerated in the trial, with no serious adverse events and no adverse events leading to discontinuation. Seventy-four of 76 dexpramipexole-treated patients and 25 of 27 placebo-treated patients completed the primary assessment phase.
“Dexpramipexole produced a significant reduction in eosinophil count, accompanied by clinically important improvements in lung function,” said Salman Siddiqui, M.D., Professor of Airway Disease at Leicester University, UK, and a co-author of the ATS 2021 poster. “We look forward to studying dexpramipexole as a potential pre-biologic alternative through the UK BEAT Severe Asthma Consortium Trials Program, funded by the National Institute for Health Research.”
Treatments approved to date for eosinophilic asthma are monoclonal antibodies requiring injection or infusion, while dexpramipexole is administered orally.
“We are pleased that EXHALE confirmed the significant eosinophil-lowering effects of dexpramipexole previously demonstrated in Phase 2 and Phase 3 clinical trials of more than 1,000 patients with other diseases,” said Michael Bozik, M.D., President and CEO of Knopp. “Even more encouraging are the clinical improvements in lung function that accompanied the targeted eosinophil depletion seen in asthma patients receiving dexpramipexole in the EXHALE trial.”
“Patients with eosinophilic asthma will welcome the addition of an oral alternative in treatment, providing the drug is safe and effective in Phase 3,” said Mary Jo Strobel, executive director of the American Partnership for Eosinophilic Disorders (APFED). “We look forward to future studies of dexpramipexole in additional eosinophil-associated diseases.”
Knopp expects to present additional analyses, including the effects of dexpramipexole on biomarkers of tissue eosinophilic inflammation and on additional measures of lung function, at a future scientific conference. In previous trials in hypereosinophilic syndrome and chronic rhinosinusitis with nasal polyps, dexpramipexole showed robust eosinophil reductions in skin, gastrointestinal, and sinus tissues.1,2
ABOUT KNOPP BIOSCIENCES LLC
Knopp Biosciences is a privately held drug discovery and development company focused on delivering breakthrough treatments for immunological and neurological diseases with high unmet need. Knopp’s clinical-stage oral small molecule, dexpramipexole, is in development for moderate-to-severe eosinophilic asthma. Knopp’s preclinical Kv7 platform is directed to small-molecule treatments for developmental and epileptic encephalopathies, other epilepsies, neuropathic pain, and tinnitus. Please visit www.knoppbio.com.
Dexpramipexole, a selective inhibitor of eosinophil maturation, is an oral small molecule drug in development by Knopp for asthma and other eosinophil-associated diseases. In hypereosinophilic syndrome, dexpramipexole has previously been shown in a Phase 2 trial to significantly reduce requirements for oral corticosteroids and in a subset of patients to produce durable disease remission. In its earlier development in amyotrophic lateral sclerosis, dexpramipexole was shown to be well tolerated in Phase 1, Phase 2, and Phase 3 trials comprising approximately 1,200 patients.
Founded in 2001, the American Partnership for Eosinophilic Disorders (APFED) is a 501(c)(3) nonprofit organization that assists and supports patients and families affected by eosinophil-associated disorders by providing education, creating awareness, supporting research, and promoting advocacy. To learn more, visit apfed.org.
This press release contains "forward-looking statements," including statements relating to planned regulatory filings and clinical development programs. All forward-looking statements are based on management’s current assumptions and expectations and involve risks, uncertainties and other important factors, specifically including the uncertainties inherent in clinical trials and product development programs, the availability of funding to support continued research and studies, the availability or potential availability of alternative therapies or treatments, the availability of patent protection for the discoveries and strategic alliances, as well as additional factors that may cause Knopp’s actual results to differ from our expectations. There can be no assurance that any investigational drug product will be successfully developed or manufactured or that final results of clinical studies will be supportive of regulatory approvals required to market a product. Knopp undertakes no obligation to update or revise any such forward-looking statements, whether as a result of new information, future events, or otherwise.
Knopp’s pipeline consists of investigational drug products that have not been approved by the U.S. Food and Drug Administration. These investigational drug products are still undergoing pre-clinical or clinical study to verify their safety and effectiveness.
1 Panch SR et al. Blood. 2018 Aug 2; 132(5): 501–509.
2 Laidlaw TM et al. Laryngoscope. 2019 Feb;129(2):E61-E66.