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First patient dosed in phase 3 study on needle- and opioid-free sedation for cataract surgery

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Melt Pharmaceuticals, Inc. announced that the first patient has been dosed in the phase 3 program of its lead investigational candidate: MELT-300, formulated as a needle- and opioid-free alternative to intravenous (IV) sedation during cataract surgery.

Refresh me on the company.

Founded in 2019 and a former subsidiary of Harrow, Inc., Melt is a clinical-stage pharmaceutical company.

Its focus: Developing and commercializing patented non-IV and non-opioid sedation and analgesic medications for (+100 million, ideally) short-term medical procedures—specifically in outpatient and in-office settings.

Its core technology: A series of combination non-opioid sedation drug formulations.

Why combine sedatives and analgesics?

The intent, according to the company, is to help patients tolerate potentially painful medical procedures (such as cataract surgery) and decrease their perceptions of pain.

Plus: Prior research has found this procedural sedation increases both procedure safety and success while decreasing procedure time.

The goal: Via this technique, for patients to “experience a depressed level of consciousness while maintaining independent and continuous airway control.”

And how will Melt be targeting this for cataract surgery?

By using the Ramsay Scale of Sedation—an evaluation method for determining a patient’s degree of sedation:

  • Level 1: Patient is awake, anxious, agitated, or restless
  • Level 2: Patient is awake, cooperative, oriented, and tranquil
  • Level 3: Patient is drowsy, with response to commands
  • Level 4: Patient is asleep with a brisk response to glabella tap or loud auditory stimulus
  • Level 5: Patient is asleep with a sluggish response to stimulus
  • Level 6: Patient has no response to firm nail-bed pressure or other noxious stimuli

For cataract surgery patients: Surgeons should want to reach a Ramsay score of 2 to 3.

Alrighty. Now talk about this investigational candidate.

MELT-300 is formulated as a non-IV, non-opioid tablet that combines fixed doses of midazolam (3 mg) and ketamine (50 mg).

The candidate is administered sublingually (under the tongue) using a proprietary, fast-dissolving delivery technology platform called Zydis (Catalent Inc.).

The technology’s purpose: To rapidly dissolve the tablet for absorption across the sublingual mucosa

How has it performed clinically so far?

Statistically superior data was reported in December 2022 from a phase 2 study comparing MET-300 against the sublingual midazolam, ketamine, and placebo, respectively, in 300+ patients undergoing cataract surgery.

  • Specifically: MET-300 was found to be statistically superior for procedural sedation against all other comparator arms. See here for details.

Gotcha. Moving on to this new study …

The phase 3 trial is a randomized, double-blind, three-arm study (NCT06383273) evaluating and comparing the following methods at a 4:1:1 ratio:

  • MELT-300
  • Sublingual midazolam
  • Sublingual placebo

The participants: 528 patients (aged 18-64) undergoing cataract surgery with lens replacement.

What’s being measured?

The primary outcome measure is the number of patients who achieve a successful procedural sedation (ie: a Ramsay score of 2 or 3), to be observed before, during, and after the surgery.

Among the secondary outcomes are the number of patients requiring rescue sedation medication and those achieving preoperative procedural sedation without a need for rescue sedation.

See here for the complete list.

So when can we expect topline data?

A topline readout is expected Q4 2024, according to the company.

What’s the significance of this?

Melt CEO Larry Dillaha, MD, noted a significant unmet need for outpatient procedural sedation that has grown over the last two decades—not to mention the use of IV-administered medications contributing to an increase in opioid use.

“We believe that MELT-300 could revolutionize procedural sedation while enhancing the patient’s experience in all sites of care by offering greater comfort without a needle stick and by reducing exposure to opioids,” he stated.

And for the future?

While the company is currently targeting cataract surgery sedation, Dr. Dillaha noted, “We believe with further development and label expansion, MELT-300 could be utilized in over 100 million annual procedures in areas such as dermatology, plastics, dental, gastrointestinal, and emergency rooms.”

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