Melt Pharmaceuticals, Inc. released positive topline data from a phase 3 study evaluating MELT-300, a non-intravenous (IV) and non-opioid tablet intended for procedural sedation during cataract surgery.
Let’s start with Melt.
Formerly a subsidiary of Harrow, Inc., Melt is a clinical-stage pharmaceutical company working to develop and commercialize patented non-IV and non-opioid sedation and analgesic medications for short-term medical procedures.
Key to these medications: A series of combination non-opioid sedation drug formulations comprising its core technology of “procedural sedation.”
Why focus on this combination?
See here for the company’s explanation.
In a nutshell: Melt’s goal is to use “procedural sedation” to help patients tolerate potentially painful medical procedures (such as cataract surgery) and decrease their perceptions of pain.
And how is this being assessed for cataract surgery, exactly?
Via an evaluation method typically used to identify a patient’s degree of sedation: the Ramsay Scale of Sedation (RSS).
This classifies sedation on a Level 1 - 6 scale, with Level 1 indicating a patient is awake, anxious, agitated, or restless, and Level 6 translating to a patient having no response to firm nail-bed pressure or other conscious stimuli.
In the case of cataract surgery: Levels 2 to 3 are desirable for patients, where they’re either awake and cooperative or drowsy but responsive to verbal commands.
Now to this candidate.
As Melt’s lead investigational candidate, MELT-300 is comprised of two fixed doses:
- Midazolam (3 mg)
- Ketamine (50 mg)
Its administration: Is conducted sublingually (i.e., under the tongue) via Zydis (Catalent Inc.), a proprietary, fast-dissolving (in as little as 3 seconds) delivery technology platform that enables absorption across the sublingual mucosa.
And the intent behind it?
MELT-300 could potentially become a safe and effective alternative to current IV-based sedation protocols for cataract surgery.
Next up: this phase 3 study.
The randomized, double-blind, three-arm study (NCT06383273) sought to evaluate the use of MELT-300 on procedural sedation in patients undergoing cataract surgery with lens replacement.
The details:
- Participants: +530 patients (aged 18-64; criteria here) enrolled at 13 U.S. clinical sites
- The setup: Three procedural sedation methods provided to patients 30(± 5) prior to surgery, compared at a 4:1:1 ratio:
- MELT-300
- Sublingual midazolam
- Sublingual placebo
- The study duration: All outcome measures analyzed on Day 1 of study (pre-, intra-, and postoperative)
- The outcome measures:
So what are these topline findings?
Per the company, MELT-300 demonstrated statistical superiority compared to both sublingual midazolam (p = 0.009) and placebo (p < 0.001) in providing successful procedural sedation.
As for rescue sedation: The number of patients who required rescue sedation was found to be “nearly two-fold higher” for patients who received sublingual midazolam versus those receiving MELT-300 (p = 0.003).
And in regards to its safety profile?
MELT-300 was noted as having a “favorable safety profile” deemed to be generally comparable to the placebo tablet.
Sounds promising … so how does this compare to previous data?
Melt CEO Larry Dillaha, MD, noted that the phase 3 findings not only strengthen the company’s patient portfolio but also confirm and complement its phase 2 efficacy and safety results.
About that phase 2 trial. MELT-300 was evaluated and compared against three forms of procedural sedation (sublingual midazolam, ketamine, and placebo) in 300+ patients undergoing cataract surgery.
- The data: The candidate was found to be statistically superior for procedural sedation versus all three comparators.
Good to hear. So what’s next for the candidate?
Per a Special Protocol Assessment (SPA) agreed to by Melt and the FDA, the phase 3 study design and positive topline data will be used to support a future regulatory submission for MELT-300.
To note: The FDA’s final decision regarding marketing approval will be based on its final review of the complete MELT-300 submission package (once submitted).