Nearly a year after first reporting positive phase 2a data on the use of TP-03 (lotilaner ophthalmic solution, 0.25%) for treating meibomian gland dysfunction (MGD), Tarsus Pharmaceuticals, Inc. announced new data from the ERSA clinical trial.
The findings were presented during the American Academy of Optometry’s (AAOpt) annual meeting in Indianapolis, Indiana, on Nov. 7.
First up: this ophthalmic solution.
TP-03 is formulated to target Demodex mite infestation, the root cause for Demodex blepharitis (DB).
Important to note: Lotilaner is what’s known as an “ectoparasiticide (anti-parasitic) agent” that essentially paralyzes and kills Demodex mites by blocking parasite-specific gamma-aminobutyric acid-gated chloride (GABA-Cl) channels.
Back up a moment: Wasn’t this FDA approved last year?
Indeed it was … in July 2023 (under the brand name XDEMVY), which was then followed by its U.S. commercial launch in August 2023.
- To note: That approved indication was for the treatment of DB—the first and currently only in the country.
What’s the recommended dosage for patients?
Its prescribing information—strictly for DB, keep in mind—indicates one drop of XDEMVY 0.25% (2.5 mg/mL) should be instilled in each eye twice daily, approximately 12 hours apart, for 6 weeks.
Check out the full details.
Alrighty, now to this phase 2 study.
Take note: Tarsus presented on data from both the phase 2 ERSA trial as well as the phase 2 RHEA study.
Here’s what to know about this MGD-targeted ERSA trial:
- The study: A randomized, two-arm, double-masked study (NCT05454956).
- Its purpose: To compare the safety and efficacy of two dosing schedules (BID and TID) of TP-03 in DB patients with MGD.
- The participants: 39 patients (aged 18+; average of 63.7 years) diagnosed with DB and MGD
And the RHEA study?
This was a randomized vehicle study among Demodex blepharitis patients diagnosed with MGD that enrolled a vehicle group.
- Its purpose: To evaluate efficacy of the vehicle on DB patients with MGD
- The participants: 40 patients (average age: 63.4)
- The setup: Three cohorts included:
- Cohort 1 (n =17) TID dosing for the first 15 days, then BID until day 85
- Cohort 2 (n =12) BID for 85 days
- Cohort 3 (n =11)TID for 85 days
And what was measured?
The endpoints gathered for both studies consisted of:
- Safety assessments
- Lower lid meibomian gland secretion score (MGSS)
- DB endpoints (collarette and erythema reduction)
- Dry eye symptoms via a visual analog scale ([VAS], 0 to 100) evaluating:
- Eye dryness
- Ocular discomfort
- Fluctuating vision
- Burning
- Itching
- Redness
Alrighty, now let’s get into this update.
Take note: The two studies were pooled for analysis after establishing between-group baseline equivalence, with no statistical differences between ERSA and RHEA observed at baseline (save for collarette grade; ERSA patients’ started off with worse at baseline [p = 0.0068]).
The company also noted that the meta-analysis results from both the BID and TID groups of the Ersa and Rhea studies were not statistically significant and combined for each study.
What to know first?
The company reported that, for the lotilaner 0.25% treatment group, “statistically significant improvements from baseline were observed at day 43 and day 85” for the following:
- Mean MGSS
- Mean number of glands secreting any liquid
- Percentage of patients achieving ≥3 glands with improvement to clear meibum (score 3, p < 0.001)
Further: There were no statistically significant improvements from baseline in the vehicle group.
Interesting … let’s talk about MGSS.
In the case of these studies: meibum scores of the 15 glands were summed up via the standardized grading system to result in the total MGSS.
With this in mind: Total scoring—MGSS—was determined by the sum of the grades for secretions from all 15 lower lid margins of each eye (range: 0 to 45):
- MGSS (31 - 45): normal to mild
- MGSS (12 - 30): moderate
- MGSS (<12): severe
To note: a 5-point improvement is considered clinically meaningful.
And how were patients’ MGSS?
For the lotilaner 0.25% group:
- Baseline: 21.9
- Day 43: 27.8
- Day 85: 33.2
For the vehicle-treated group:
- Baseline: 22.1
- Day 43: 23.3
- Day 85: 23.1
What about meibum quality?
Meibum quality scoring was based on a grading scale of 0 to 3.
- Grade 0: no meibum secretion
- Grade 1: inspissated/toothpaste meibum
- Grade 2: Cloudy meibum
- Grade 3: Clear meibum
The percentage of patients who achieved ≥ 3 glands with improvement—from baseline—to a clear meibum (ie: a score of 3) included:
At Day 43 (p < 0.01):
- Lotilaner 0.25% group: 44.7
- Vehicle group: 17.6
At Day 85 (p < 0.0001):
- Lotilaner 0.25% group: 78.9
- Vehicle group: 18.1
And in regards to collarette reduction?
The following percentages were observed for a collarette reduction down to grade 0 (meaning 0-2 collarettes/lid) between the two groups at Day 43 and Day 85, respectively (p < 0.0001):
- Lotilaner 0.25% group: 42%, 66%
- Vehicle group: 0%, 0%
And the following collarette reduction to grade 0-1 (0-10 collarettes/lid) was noted at Day 43 and Day 85, respectively (p < 0.0001):
- Lotilaner 0.25% group: 82%, 100%
- Vehicle group: 6%, 8%
Did patient symptoms improve?
Yes! Let’s zero in on their symptoms: patient-reported burning and fluctuating vision, specifically.
Burning
- At baseline
- TP-03 mean VAS score = 35.4 (vs 46.0 for vehicle) (p < 0.01)
- At Day 43
- TP-03 mean VAS score = 20.0 (vs 34.8 for vehicle) (p < 0.01)
- At Day 85
- TP-03 mean VAS score = 10.5 (vs 31.6 for vehicle) (p < 0.05)
Fluctuating vision
- At baseline
- TP-03 mean VAS score = 46.5 (vs 51.9 for vehicle) (p < 0.01)
- At Day 43
- TP-03 mean VAS score = 22.2 (vs 40.1 for vehicle) (p < 0.01)
- At Day 85
- TP-03 mean VAS score = 13.1 (vs 30.8 for vehicle) (p < 0.05)
To note: A VAS score of 40-50 is considered moderate in severity, while a score of 10 or lower is considered very mild / normal.
And how did itching and redness fare?
Also improved!
Itching
- At baseline
- TP-03 mean VAS score = 47.0 (vs 52.8 for vehicle) (p < 0.01)
- At Day 43
- TP-03 mean VAS score = 16.9 (vs 42.6 for vehicle) (p < 0.01)
- At Day 85
- TP-03 mean VAS score = 11.4 (vs 40.5 for vehicle) (p < 0.01)
Redness
- At baseline
- TP-03 mean VAS score = 43.6 (vs 42.5 for vehicle) (p < 0.01)
- At Day 43
- TP-03 mean VAS score = 18.6 (vs 38.9 for vehicle) (p < 0.01)
- At Day 85
- TP-03 mean VAS score = 12.2 (vs 32.6 for vehicle) (p < 0.01)
Any adverse events?
A total of 5.1% (two patients) and 15% (six patients) in the ERSA and RHEA studies, respectively, were reported to have treatment-related ocular adverse events (AEs)—however, no serious treatment-related AEs were noted for either of the studies.
A few of those AEs included:
- In ERSA:
- Conjunctivitis
- Ocular discomfort
- In RHEA:
- Conjunctival hemorrhage
- Conjunctival irritation
- Eye irritation
- Ocular hyperemia
- Punctate keratitis
- Visual impairment
So how does this data compare to previously-reported findings?
Similar to that topline data reported in December 2023, TP-03 was deemed “promising” for treating MGD in patients with Demodex mites.
Specifically: The formulation demonstrated “statistically significant and clinically meaningful improvements” when compared to baseline in two key areas measured:
- Presence and quality of liquid secretion (according to the MGSS scoring range of 0-45)
- Number of glands producing normal liquid (as measured in the central 15 glands of the lower eyelid)
- See some data points here—as well as the statistically significant findings collected from collarette cure and lid margin erythema data.
And what did investigators have to say about this?
Ultimately, the researchers concluded that “lotilaner ophthalmic solution 0.25% demonstrated statistically significant improvements in measures of meibum quality, meibomian gland function, and patient-reported outcomes at 6 weeks and 12 weeks compared to baseline and vehicle.”
Further: Lotilaner 0.25% was well tolerated with a similar safety profile to that of the vehicle group.
Go on …
Ben Gaddie, OD, presenter of the data during AAOpt, noted the significance of the data for DB patients presenting with MGD.
“(The data) show that treating a patient’s DB with XDEMVY not only has the potential to improve objective measures of MGD, but may also result in meaningful improvements in symptoms, including fluctuating vision and itching – two very common symptoms my patients present with.”
Editor’s note: These findings were based on the AAOpt presentation by Ian Benjamin Gaddie, OD, Patrick Vollmer, OD, Leslie O’Dell, OD; Stephanie Baba, OD; and Kavita Dhamdhere, MD, PhD.