Tarsus Pharmaceuticals, Inc. reported findings from the Ersa phase 2a clinical trial measuring TP-03 for the treatment of meibomian gland disease (MGD) in patients with Demodex mites.
Tell me more about TP-03.
TP-03 (lotilaner ophthalmic solution, 0.25%) is designed to target Demodex mite infestation, the root cause for Demodex blepharitis.
To note, lotilaner is an ectoparasiticide (anti-parasitic) agent that paralyzes and exterminates Demodex mites by blocking parasite-specific gamma-aminobutyric acid-gated chloride (GABA-Cl) channels.
And isn’t this already approved?
Yes… but not for MGD. The medication was approved by the FDA in July 2023 to treat Demodex blepharitis under the brand name XDEMVY.
See our coverage here, including a one-on-one interview with Tarsus CEO and Chairman Bobby Azamian.
In August 2023, XDEMVY was commercially launched in the U.S. (details here).
What’s the recommended dosage?
Based on its prescribing info for the treatment of Demodex blepharitis, one drop of XDEMVY 0.25% (2.5 mg/mL) can be instilled in each eye twice daily (approximately 12 hours apart) for 6 weeks.
See here for the full details.
Gotcha. So talk about the phase 2a study.
The randomized, two-arm, double-masked, multicenter, parallel pilot study (NCT05454956) compared the safety and efficacy of two dosing schedules of TP-03 (compared to vehicle) in a total of 40 patients (aged 18+) with MGD.
And the dosing schedules?
- TP-03 administered twice (BID) a day and three times a day (TID).
- TP-03 vehicle administered once a day (QD) in the BID dosing arm
- TP-03 administered twice a day in patients in the BID dosing arm and three times a day in patients in the TID dosing arm
All dosing schedules were followed for approximately 85 days.
And what was measured?
Per Clinical Trials, the primary outcome measure was treatment-emergent adverse events (TEAEs) after 85 days.
Other outcome measures, also measured at 85 days, included change from baseline in:
- Lower lid meibomian gland secretion score
- Lid margin erythema
- Tear breakup time (TBUT) assessed via slit lamp
- Dry eye symptoms via a visual analog scale ([VAS], 0 to 100) evaluating:
- Eye dryness
- Ocular discomfort
- Fluctuating vision
- Burning
- Itching
- Redness
*Note: these were assessed for one week prior to the in-office visit.
Now these findings.
Per Tarsus, TP-03 demonstrated “statistically significant and clinically meaningful improvements” when compared to baseline in two measures:
- Presence and quality of liquid secretion according to the Meibomian Gland Secretion Score (MGSS, scoring range of 0-45)
- Number of glands producing normal liquid (as measured in the central 15 glands of the lower eyelid)
Give me some numbers.
A statistically significant and clinically meaningful increase was noted in the mean MGSS of 10.5 (±1.6 standard error [SE]) and 11.7 (±1.9 SE) for the BID and TID arms, respectively at Day 85.
This increase was also observed in the mean number of meibomian glands secreting normal liquid, with a difference of 4.8 (±0.8 SE) and 5.3 (±1.1 SE) for the BID and TID arms, respectively.
What happened with the lid margin?
Collarette cure and lid margin erythema data were also statistically significant, which was on par with prior TP-03 studies—such as Saturn-1, Saturn-2, and Saturn 2b/3 for Demodex.
Any differences noted between dosing schedules?
Nope, the company reported no significant difference between dosing TP-03 BID or TID.
Any adverse side effects?
No on this as well. In fact, TP-03 was found to be “well-tolerated.”
Just for comparison: In clinical trials, 10% of patients treated with XDEMVY (for Demodex) encountered stinging and burning, while less than 2% experienced chalazion/hordeolum and punctate keratitis.
Significance?
These results, “underscore the potential of TP-03 to address the underlying cause of disease,” stated Tarsus’s Dr. Azamian.
Tarsus will be using this data to continue discussions with the FDA on next steps for potential market approval and a second indication for TP-03.