Novaremed AG announced the completion of patient enrollment in a National Institutes of Health (NIH)-sponsored Phase 2b clinical trial evaluating its investigational non-opioid drug NRD.E1 for treating chronic pain associated with diabetic peripheral neuropathy. The last patient first visit (LPFV) marks the enrollment of 127 adult and elderly patients in the randomized, placebo-controlled trial, with topline data expected in Q4 2025.
The Phase 2b EN21-01 trial (ClinicalTrials.gov identifier NCT05480228) is funded by the NIH Helping to End Addiction Long-term Initiative (HEAL Initiative) and represents a significant milestone in developing non-opioid alternatives for chronic pain management. Study completion, with the last patient's last visit, is anticipated in Q3 2025.
Study Design and Objectives
The 12-week, multicenter, randomized, double-blind, placebo-controlled clinical trial has a primary objective to demonstrate that a once-daily dose of NRD.E1 80 mg is superior to placebo in relieving chronic pain among patients with painful diabetic peripheral neuropathy (PDPN). The study will also assess safety, tolerability, pharmacokinetics, and the compound's impact on sleep and quality of life.
"Completing the study enrollment is a major milestone for us," said Jessica Robinson-Papp, MD, MS, FAAN, Lead Primary Investigator and Professor at the Icahn School of Medicine at Mount Sinai. "Achieving it was a deeply collaborative effort including multiple academic medical centers, the NIH, and the Novaremed team. It wasn't always easy, but the goal of developing desperately needed new non-opioid pain therapies was an ongoing source of inspiration."
Novel Mechanism of Action
NRD.E1 (or NRD135S.E1) is an orally active small molecule with a novel mechanism of action that differs from approved pain therapies. Notably, it does not bind to opioid receptors or other receptors associated with opioid mode of action, positioning it as a potential non-addictive alternative for chronic pain management.
The drug has demonstrated favorable safety and tolerability profiles in completed Phase 1 studies, showing tolerance as a single dose up to 1200 mg and repeated doses of 300 mg/day for five consecutive days. The studies revealed dose-dependent absorption, small increased exposure when administered with food, and no relevant accumulation after oral administration.
Promising Phase 2a Results
The current Phase 2b trial builds on encouraging Phase 2a proof-of-concept results. The earlier study was a randomized, double-blind, placebo-controlled, dose-finding trial in 88 patients with moderate to severe PDPN. Conducted over a 3-week treatment period, the study investigated NRD.E1 at doses of 10, 40, or 150 mg/day compared to placebo and showed clinically relevant placebo-corrected pain reductions at the 40 and 150 mg/day doses.
Addressing Unmet Medical Need
The development of NRD.E1 addresses a significant gap in current treatment options for PDPN. According to the company, peripheral nerve injury from various etiologies may result in chronic and severe intractable neuropathic pain, with PDPN representing the most common form of neuropathic pain with high unmet medical need.
Worldwide, an estimated 8.1 million diabetes patients with PDPN requiring treatment do not obtain sufficient pain relief with current therapies. Many currently available products for treating chronic neuropathic pain have limited efficacy and are often poorly tolerated.
"Currently, approved medications for painful diabetic peripheral neuropathy provide inadequate pain relief and are associated with many intolerable side effects," said Camilla Mittelholzer, PhD, CSO and Head of R&D at Novaremed. "Completing enrollment in this study brings us closer to Phase 2b study results, which hopefully will support the continued development of NRD.E1 as a novel, non-opioid treatment option for patients experiencing chronic pain."
Regulatory Recognition
NRD.E1 has received significant regulatory recognition for its potential. The US FDA granted Fast Track Designation to NRD.E1 for the treatment of PDPN, and the NIH selected it as the only oral agent to be included in the EPPIC-Net (Early Phase Pain Investigation Clinical Network) master protocol to assess treatments for PDPN.
The EPPIC-Net is part of the NIH HEAL Initiative and seeks to enhance the treatment of acute and chronic pain while reducing reliance on opioids by accelerating early-phase clinical trials of non-addictive treatments for pain. The NIH HEAL Initiative represents an NIH-wide effort to speed scientific solutions to the overdose epidemic, including opioid and stimulant use disorders, and the crisis of chronic pain.
