Nacuity Pharmaceuticals, Inc., recently announced that the first patient has been dosed in the global, confirmatory phase 3 SLO-RP Preserve clinical trial of NPI-001 for the treatment of retinitis pigmentosa (RP) associated with Usher syndrome.
Give me a refresher on Nacuity.
The Texas-based, clinical-stage pharmaceutical company is focused on developing prescription antioxidant therapies targeting oxidative stress-induced diseases.
Nacuity is supported and funded in part by the Foundation Fighting Blindness and its venture arm, the Retinal Degeneration (RD) Fund, for several of its clinical programs—check them out here.
And while NPI-001 is the company’s lead asset, it is also currently developing NPI-002, an intravitreal (IVT) implant for delay of cataract progression.
- Its clinical status: currently undergoing a phase 1/2 study (NCT05026632) assessing its safety and efficacy.
Can we take a closer look at oxidative stress?
Absolutely. This is essentially an imbalance of free radicals and antioxidants in the human body that can lead to cell damage.
- importantly, it plays a key role in the onset of such chronic and degenerative conditions like neurological and cardiovascular diseases, as well as cancer, to name a few.
And in the context of ocular disease: Oxidative stress also has a significant impact on the development of several ocular diseases and conditions, including: RP, cataract, and age-related macular degeneration (AMD).
- See here for a more in-depth look.
Now to NPI-001.
The investigational candidate is a proprietary, Good Manufacturing Practice (GMP)-grade formulation of (N-acetylcysteine amide [NACA]) tablets intended to address oxidative stress associated with RP (in Usher syndrome).
How it does this: by boosting glutathione—a strong endogenous antioxidant in the body—to prevent chemically-aggressive oxygen molecules from causing retinal cell damage.
- Take note: Nacuity noted that NPI-001 has demonstrated this mechanism of action (MOA) in preclinical trials and animal studies, which also found that it preserved photoreceptor cells and functionality.
And what’s its regulatory status?
The NACA tablet has received multiple FDA designations, including:
- Fast Track
- Breakthrough Therapy
- Orphan Drug
Why this is important: The latter designation provides 7 years of FDA regulatory exclusivity for the product upon regulatory approval.
Noted. So how has NPI-001 performed in previous trials?
A phase 1 study among healthy patients, in which the candidate was self-administered in its tablet form, concluded with no serious adverse events reported.
More recently: NPI-001 was also evaluated in the phase 1/2 SLO-RP trial (NCT04355689) among nearly 50 adult patients diagnosed with Usher syndrome.
- See here for details on the 24-month study’s setup and primary outcome measure.
Can we get a rundown on those results?
A few highlights from this reporting:
- NPI-001 slowed photoreceptor loss by over 50% over a 2-year period
- After daily dosings of NPI-001, loss of photoreceptors was significantly lower than with placebo (beginning at the 6-month mark and continuing through to 24 months)
- NPI-001 was safe and well-tolerated at dose levels of 500 mg/day—with +80% compliance for planned dosing
Moving on to the SLO-RP Preserve trial.
The 24-month, randomized, double-masked phase 3 study (NCT07710196) will enroll up to 80 adult participants who will self-administer a 250mg NPI-001 or placebo tablet twice a day (BID) orally and complete nine in-clinic visits.
- The goal: to evaluate whether NPI-001 can slow disease progression by reducing photoreceptor loss.
- Primary outcome measure: ellipsoid zone (EZ) area rate of change from baseline to 24 months.
Note: The Inherited Retinal Degeneration Clinic at the Retina Foundation of the Southwest in Dallas, Texas, and other sites in the U.S. and Australia are actively enrolling additional patients.
- See here for which clinic sites patients can enroll at.
Any comments from the company?
“We’re excited that the first patient has been dosed in this important confirmatory study,” said Mark Pennesi, MD, PhD, chief medical officer of Nacuity—and principle investigator of the SLO-RP Preserve trial. and director of the Inherited Retinal Degeneration Center at the Retina Foundation.
- Dr. Pennesi is also the director of the Inherited Retinal Degeneration Center at the Retina Foundation.
“Patients living with RP associated with Usher syndrome face progressive vision loss with limited treatment options,” he added. “Building on the encouraging findings observed to date, we look forward to further evaluating the potential of NPI-001 to slow disease progression and preserve vision in this phase 3 trial.”
So! When can we expect to see some data from this?
As the SLO-RP Preserve trial has a primary completion date of April 2029, topline data is likely to come sometime between now and then …
And in the meantime: The company is expected to report proof-of-concept results by early 2026 for NPI-002—so stay tuned.