Early Data Support Continued Development of NVG-2089 as IVIg Alternative in CIDP

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Key Takeaways

NVG-2089 demonstrated a favorable safety profile in phase 1, with no serious adverse events and linear pharmacokinetics across tested doses.
The drug aims to replicate IVIg's anti-inflammatory effects at significantly lower doses, potentially reducing infusion time to about one hour.
The phase 2 INVGOR trial will assess NVG-2089 in CIDP patients, focusing on safety and efficacy, with a more patient-friendly design.
INVGOR includes both treatment-experienced and treatment-naïve patients, aiming to provide robust data for potential progression to a phase 3 study.

Nuvig's NVG-2089 shows promise in CIDP treatment, offering a safer, more efficient alternative to IVIg with a patient-friendly trial design.

Pamela Conley

Recently presented data from a phase 1 study of healthy volunteers demonstrated the safety profile of investigational NVG-2089 (Nuvig Therapeutics), coupled with pharmacokinetic (PK) data that suggest efficacy may be achieved with up to 4-week dosing intervals. NVG-2089, a recombinant human IgG1 Fc-F241A-targeting therapeutic, will be tested in the phase 2 INVGOR study, a currently enrolling trial of patients with chronic inflammatory demyelinating polyneuropathy (CIDP).^1,2

Across both single (SAD)- and multiple-ascending dose (MAD) cohorts, NVG-2089 was considered well tolerated, with no serious adverse events (AEs) observed, nor any early terminations related to AEs. Overall, the exposure was linear across the range of tested doses, with a half-life ranging from 11-12 days. Notably, investigators observed no clinically significant changes in vital signs, electrocardiogram, or clinical laboratory parameters across any of the doses evaluated.

"NVG-2089 is designed to recapitulate the anti-inflammatory activity of the sialated component of IVIg at a 10-to-20-fold lower dose,” Pamela Conley, chief scientific officer and interim chief executive officer at Nuvig, told NeurologyLive^®. "IVIg is the standard of care in CIDP, but its often a difficult therapy to tolerate on a chronic basis, due to the fact that it’s a very large dose of protein and a large volume, meaning it takes a long time for infusions, sometimes 1-2 days. With NVG-2089, we believe we can deliver the equivalent of high-dose IVIg, but in a much lower volume, with about a 1-hour infusion time that is typically required for IVIg."

The SAD cohort, testing single intravenous infusion doses of 9, 30, 100, 250, or 500 mg/kg NVG-2089, comprised 40 healthy individuals, whereas the MAD included 16 participants who were randomly assigned to 3 biweekly doses of 150 or 300 mg/kg of NVG-2089 or placebo. During the trial, FcγRIIB upregulation on conventional dendritic cells and expansion of activated CD39+ Tregs was observed in peripheral blood at all dose levels examined, with no clear dose response. Of note, FcγRIIB upregulation correlated with specific cytokine changes.

"Unlike FcRn inhibitors, which have been evaluated and recently approved for CIDP, those medications broadly reduce IgG levels," Conley added. "Complement inhibitors, which are also being studied, target a single pathway. Our molecule and mechanism modulates several key immune mechanisms on B cells, myeloid cells, and on T-regulatory cells. It offers a much broader, more balanced approach, and it’s not an immunosuppressive approach, like eliminating your B cells or inhibiting your T cells completely."

Based on these promising early-stage data, along with preclinical model studies, Nuvig is advancing NVG-2089 to the phase 2 INVGOR trial, a multicenter, global study testing the agent in 60 patients with CIDP. Spanning across 40 sites globally, the trial will include those currently treated with IVIg who will transition to NVG-2089 as well as treatment-naïve patients who have yet to receive therapy.

INVGOR will primarily focus on safety, but also include other efficacy end points, such as the proportion of patients achieving evidence of clinical improvement (ECI). The 14-week study will also record the percentage of IVIg treatment experienced patients achieving ECI at week 14 or stability of disease as measured by adjusted INCAT scores between weeks 4 and 14.

Alan Glicklich

Regarding INVGOR, "We’ve taken a lot of learnings from previous trials in CIDP,” Alan Glicklich, MD, chief medical officer at Nuvig, told NeurologyLive. “Some of the earlier trials had been a little less patient-friendly. They required patients to wash out of their existing treatment and then get worse before they get treated. After talking to KOLs, CIDP patient groups, and investigators, one of the messages that was loud and clear was that nobody really likes this kind of design, and it’s very hard on patients."

He went on to say, "We’ve designed a trial that’s more patient-friendly, where treatment-experienced patients get treated with active drug following a 3-week period after their last dose from IVIg to our drug (NVG-2089). We’re trying to keep the patient in mind for this study and for future studies in CIDP. By doing the study this way, we’ll collect data on improvement in treatment-naïve patients, or stability or improvement in treatment experienced patients. There’s lots of data on historical placebo response rates in CIDP, and we believe this study will provide robust data that will help us with the decision to go to the next study, the pivotal (phase 3) study."