After kicking off 2025 with Fast Track designation from the FDA for NPI-001 (N-acetylcysteine amide [NACA]) tablets, an investigational therapy for retinitis pigmentosa (RP) treatment, Nacuity Pharmaceuticals has received yet another designation: Breakthrough Therapy.
Where to start with this?
We’ll begin with Nacuity—a Texas-based, clinical-stage pharmaceutical company developing prescription antioxidant therapies targeting oxidative stress-induced diseases.
- The company 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).
Explain the focus on oxidative stress.
This is essentially an imbalance of free radicals and antioxidants in the human body that can lead to cell damage—and, importantly, 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.
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.
And NPI-001?
The investigational candidate is a proprietary, Good Manufacturing Practice (GMP)-grade formulation of 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: NPI-001 demonstrated this mechanism of action (MOA) in preclinical trials and animal studies, according to Nacuity, which also found that it preserved photoreceptor cells and functionality.
Interesting … any other clinical data to support its MOA?
You mean any non-pre-clinical trials? Yes indeed. The candidate was further evaluated in a later phase 1 study among healthy patients, in which it was self-administered in its tablet form.
- Those findings: The study concluded with no serious adverse events reported.
And, in more recent news, NPI-001 is also being studied 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.
Any data reported from that yet?
Yes, actually! The company released positive data just last month.
The 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
Sounds promising! Now to this designation—which is its … second?
Third, actually. While we previously covered NPI-001 receiving Fast Track designation in January, the candidate had already received Orphan Drug designation prior to that.
About Breakthrough Therapy designation: This is granted based on preliminary clinical evidence and is intended to expedite the development and review process for drugs designed to treat a serious or life-threatening disease (such as RP).
- Even further, it aims to:
- Enhance FDA communication and collaboration with a company
- Streamline a drug’s clinical trials
- Reduce (expedite) a drug’s development timeline
And take note: A drug granted this designation is also eligible for all Fast Track designations offered to investigational drugs by the FDA.
So what’s next?
Securing Breakthrough Therapy designation gives Nacuity even greater privileges and an expedited pathway to regulatory approval for NPI-001 … so stay tuned for more news on this in the near future!