PL9643_Dosage, benefits & legal status
Also known as PL-9643, PL9643 ophthalmic solution
An investigational eye drop whose phase 2 missed both primaries outright, whose phase 3 result depends on which analysis you read, and which its developer has now licensed out.
Common vial size is what vendors typically sell, not a recommendation. Enter your own vial in the calculator.
What is PL9643?
Plain language first. The technical label stays, but it never stands alone.Overview
It is an eye drop in the same drug family as PT-141 and the melanotans, aimed at the inflammation behind dry eye rather than at tear volume. A 160-patient phase 2 missed both of its primary endpoints. The 575-patient phase 3 then reported no significance on either co-primary endpoint in the planned analysis, and significance on the pain endpoint only after the analysis was adjusted for age and sex.
PL9643 is a synthetic melanocortin receptor pan-agonist formulated as an eye drop for dry eye disease, developed by Palatin Technologies. Its published description is that it is active at melanocortin receptors but not at MC2R, the one that drives cortisol release; its sequence and its potency at each individual receptor have not been disclosed.
What it's used for
An investigational prescription eye drop for moderate to severe dry eye disease. It is not approved and is not sold anywhere.
How does PL9643 work?
What it does in the body, and where.Melanocortin receptors are better known on this site for libido and tanning, through PT-141 and the melanotans. The eye carries them too, and the melanocortin system there is thought to hold inflammation in check rather than drive pigment or arousal.
- 01A pan-agonist that skips MC2RThe published description is that PL9643 acts at melanocortin receptors but not at MC2R, the receptor in the adrenal gland that releases cortisol. Skipping it is the point: it avoids a steroid-like hormonal effect. Which of the remaining receptors it hits, and how strongly, has not been published.
- 02Aimed at inflammation, not tear volumeDry eye drugs split into ones that add or hold moisture and ones that calm the inflammation that damages the surface. This is the second kind, so its endpoints were surface staining and pain rather than tear production.
- 03Why the endpoints matterDry eye trials have to move both a sign a clinician can measure and a symptom the patient reports. Many drugs move one and not the other. In this program the sign endpoint has not reached significance in either trial.
What else is it used for?
Each group carries its own evidence level.Approved means regulators have cleared it for that purpose. Investigational means it is in trials. Early research means it is being studied and is not established.
The published phase 2
peer-reviewed-human- Human trial160 patients, 12 weeks, 1 microgram per mL three times daily. Both primary endpoints missed: corneal staining P = 0.4363 and ocular discomfort P = 0.8360.
- Human trialA post hoc subgroup of 53 people with moderate to severe disease showed nominal improvements in staining and tear film breakup time. The authors state these were not adjusted for multiple comparisons and call them hypothesis-generating.
- Human trialSide effects were more common on placebo than on drug, and instillation-site pain occurred only in the placebo group.
The phase 3, and which analysis you read
Investigational- Human trialMELODY-1 enrolled 575 patients and is recorded as completed. Everyone got vehicle for a 2-week run-in, then 12 weeks of treatment.
- Human trialThe company states that in the planned unadjusted analyses, neither co-primary endpoint nor any secondary endpoint reached significance.
- Human trialAfter the intent-to-treat analysis was adjusted for age and sex, the pain endpoint reached p<0.025, and the company reports several secondary symptom endpoints reaching the same threshold. The staining endpoint showed positive effects over vehicle without reaching significance, and no p-value was given for it.
- No dataThe registry defines the pain co-primary within a hyper-responder subgroup, people who scored 4 or more on a pain scale within 30 minutes of being put in a controlled adverse environment chamber, a room set to low humidity with moving air and a visual task. That is narrower than the whole trial population.
- No dataPalatin has since issued further responder and symptom-resolution analyses. Those are additional looks at the same completed trial, not a new one.
- RegulatoryIn August 2024 the FDA confirmed it found the protocols and endpoints acceptable for two further pivotal trials, MELODY-2 and MELODY-3. Neither has started.
- RegulatoryPalatin sublicensed PL9643 in dry eye to Altanispac Labs in January 2026, recognizing about $3.8 million as cancellation of debt rather than cash, and now lists the program among candidates it is out-licensing rather than developing itself.
PL9643 is often summarized as having hit one of two phase 3 endpoints. The company's own release says the planned unadjusted analyses missed both co-primary endpoints and every secondary endpoint, and that the pain endpoint reached significance only after the intent-to-treat analysis was adjusted for age and sex. An adjustment applied after a planned analysis fails is a different claim from a prespecified win. The pain endpoint is also registered within a hyper-responder subgroup rather than the full population. The earlier 160-patient phase 2 is sometimes described as positive; it missed both primaries, at P = 0.4363 and P = 0.8360, and what was positive was a post hoc subgroup of 53 people.
The published record
Papers and trials about PL9643
4 papers tagged human · 1 not reviews or lab · 1 clinical trial publications
2 registered trials · none with posted results
Furthest stage reached: Phase 3, completed, no results posted
Counted from Europe PMC indexing, not read by a person; a human tag can land on reviews, commentary or lab papers; clinical trial publications is the narrower count.
At a glance
Four things to know about PL9643
Evidence
Investigational
Category
Healing and recovery
Common vial
Varies
Half-life
Not published
How much, and do you cycle it?
The range, and whether you take breaks.1 microgram per mL, one drop in each eye, in the published phase 2, three times daily (phase 2 schedule). Continuous while taken Trial dose
Dry eye treatment is daily and ongoing. The trials dosed for 12 weeks with no break, and the phase 3 ran a 2-week run-in on vehicle before treatment started, to pick who entered the trial.
Not publishedNo figure
No pharmacokinetic data have been published for PL9643. For an eye drop the question is usually how long it stays on the eye surface rather than in the blood, and neither has been reported.
You can compare this against the whole library to see where it sits.
What does it cost?
Typical dose and cost, in plain numbers.PL9643 is not injected
It is taken as eye drops.
How do you store it?
Before mixing, and after.Eye drops: store them as the label or trial instructions say.
PL9643 is used as eye drops, not mixed from a powder. Keep the bottle or single-use vials as the label or trial instructions say, do not let the tip touch the eye or anything else, and throw away a single-use vial once it has been opened.
What are the side effects and cautions?
Known cautions and warnings for this compound.Who should avoid it
- Any use outside a trial: no product exists and nothing is sold
- Anything described as a melanocortin eye drop from a supplier: this is a sterile ophthalmic formulation and nothing of the kind is on sale
Stop and get help
- Not applicable outside a trial
Common effects
- Ocular treatment-related events in 5.6% on drug against 6.3% on vehicle in the 575-patient phase 3
- In the phase 2, 20.0% of the drug group and 27.5% of the placebo group had any side effect
Where this page says nothing is established, that means nobody has studied it, not that a compound is safe.
Is PL9643 approved?
And where the numbers on this page come from.No. PL9643 is not approved anywhere and is currently in company-run clinical trials. There is no legal route to obtain it outside a trial.
- Approval statusInvestigational
- RouteAs eye drops
- Checked23 October 2026
- DoseFrom published clinical trials. Not approved by a regulator for this dose.
- Vial sizeFrom what vendors typically list; not a recommendation.
- Sources
What has happened recently
Not approved anywhere, and nothing is sold. MELODY-1 (NCT05201170) is registered as a completed phase 3 with 575 participants, run from December 30, 2021 to a primary completion date of September 1, 2023. The registry's two co-primary endpoints are conjunctival lissamine green staining at week 12 and ocular pain by visual analog scale in a defined hyper-responder subgroup. Palatin's results release says the planned unadjusted analyses missed both co-primary and all secondary endpoints, and that after the intent-to-treat analysis was adjusted for age and sex the pain endpoint and several secondary symptom endpoints reached p<0.025. In August 2024 the FDA confirmed the protocols and endpoints for two further pivotal trials, MELODY-2 and MELODY-3, neither of which has started; Palatin's pipeline lists them as a potential 2026 initiation. In January 2026 Palatin sublicensed PL9643 in dry eye to Altanispac Labs, recognizing about $3.8 million in license revenue as cancellation of debt, and the program now sits under its out-licensed candidates. There is no FDA substance record, no INN and no published sequence.
You can compare this against the whole library, or read how to check a seller.
What else is like PL9643?
Others in Healing and recovery, side by side.If you're weighing PL9643, it's worth reading Plecanatide (Trulance), Redasemtide, and Retinalamin in the same class.
An investigational eye drop whose phase 2 missed both primaries outright, whose phase 3 result depends on which analysis you read, and which its developer has now licensed out.
- Dose
- 1 microgram per mL, one drop in each eye, in the published phase 2
- How often
- Three times daily (phase 2 schedule)
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- Dose
- 3 mg once daily (label)
- How often
- Once daily, with or without food
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- Dose
- 0.75 to 1.5 mg/kg daily for 5 days, or weekly (trial doses)
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- Daily for 5 days, or weekly for 4 weeks (trials)
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- Dose
- 5 up to 10 mg per day
- How often
- Daily, in 10-day courses
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Sources
- MELODY-1 trial record, ClinicalTrials.gov NCT05201170(2023)Completed phase 3, 575 participants actual, started December 30, 2021, primary completion September 1, 2023, sponsor Palatin Technologies. Co-primary endpoints: conjunctival lissamine green staining at week 12, and ocular pain by visual analog scale in a hyper-responder subgroup defined at Visit 2.
- Palatin MELODY-1 results release, February 28, 2024(2024)States that in the unadjusted planned analyses the co-primary and secondary endpoints did not reach significance, and that pain reached p<0.025 after the intent-to-treat analysis was adjusted for age and sex. The staining endpoint showed positive effects without significance. Ocular treatment-related events 5.6% against 6.3%.
- Evans et al., phase 2 results, Journal of Ocular Pharmacology and Therapeutics, 2023(2023)160 patients randomized 1:1. Both primary endpoints missed: inferior corneal staining difference -0.11 (95% CI -0.38 to 0.16, P = 0.4363) and ocular discomfort 0 (95% CI -0.3 to 0.4, P = 0.8360). A post hoc moderate-to-severe subgroup of 53 showed nominal improvements the authors call hypothesis-generating.
Beyond these, 4 records are indexed. Browse the records