PMID- 37677000
OWN - NLM
STAT- MEDLINE
DCOM- 20231106
LR  - 20231119
IS  - 1557-7732 (Electronic)
IS  - 1080-7683 (Print)
IS  - 1080-7683 (Linking)
VI  - 39
IP  - 9
DP  - 2023 Nov
TI  - Efficacy and Safety of the Melanocortin Pan-Agonist PL9643 in a Phase 2 Study of 
      Patients with Dry Eye Disease.
PG  - 600-610
LID - 10.1089/jop.2023.0056 [doi]
AB  - Purpose: The melanocortin receptor pan-agonist PL9643, a potential therapy for 
      ocular diseases, was investigated in a phase 2, 12-week study in patients with 
      dry eye disease (DED). Methods: This was a placebo-controlled study evaluating 
      efficacy and safety of thrice-daily PL9643. Placebo (vehicle) was similar to 
      tears. Primary endpoints were intra-patient changes in inferior corneal 
      fluorescein staining and ocular discomfort after 12 weeks. Secondary endpoints 
      were changes in additional DED signs or symptoms. Multiple secondary endpoints 
      were not adjusted for multiplicity. Patients with moderate or severe DED were 
      analyzed in addition to the overall intent-to-treat (ITT) population. Results: In 
      the ITT population (n = 160) the PL9643 group did not demonstrate significant 
      treatment difference versus placebo at week 12/day 85 for the primary endpoints 
      (P > 0.05). In patients with moderate or severe DED (n = 53), PL9643 treatment 
      demonstrated either nominally significant (P < 0.05) or trending (P < 0.1) 
      improvement over placebo in mean change from baseline at week 12/day 85 in 
      several sign endpoints, including fluorescein staining in inferior, superior, 
      corneal sum, and total sum regions; Lissamine Green staining in temporal, nasal, 
      conjunctival sum, and total sum regions; and tear film breakup time. Conjunctival 
      redness also showed (nonsignificant) improvement at week 12/day 85. There were no 
      drug-related adverse events (AEs) and no drug-related discontinuations. 
      Conclusions: PL9643 showed no significant efficacy for the ITT population; 
      however, efficacy results across several signs and symptoms in the subpopulation 
      of moderate to severe DED patients, the low number of ocular AEs, and no 
      tolerability issues suggest that PL9643 shows promise as a therapeutic for DED. 
      Clinical Trial Registration number: NCT04268069.
FAU - Evans, David
AU  - Evans D
AD  - Total Eye Care, Memphis, Tennessee, USA.
FAU - Kenyon, Kenneth
AU  - Kenyon K
AD  - Tufts University School of Medicine and New England Eye Center, Boston, 
      Massachusetts, USA.
FAU - Ousler, George
AU  - Ousler G
AD  - Ora, Inc., Andover, Massachusetts, USA.
FAU - Watson, Michael
AU  - Watson M
AD  - Ora, Inc., Andover, Massachusetts, USA.
FAU - Vollmer, Patrick
AU  - Vollmer P
AD  - Vita Eye Clinic, Shelby, North Carolina, USA.
FAU - McLaurin, Eugene B
AU  - McLaurin EB
AD  - Total Eye Care, Memphis, Tennessee, USA.
FAU - Torkildsen, Gail
AU  - Torkildsen G
AD  - Andover Eye Associates, Andover, Massachusetts, USA.
FAU - Winters, Jason
AU  - Winters J
AD  - Palatin Technologies, Inc., Cranbury, New Jersey, USA.
FAU - Dodd, John
AU  - Dodd J
AD  - Palatin Technologies, Inc., Cranbury, New Jersey, USA.
FAU - Jordan, Robert
AU  - Jordan R
AD  - Palatin Technologies, Inc., Cranbury, New Jersey, USA.
FAU - Wills, Stephen T
AU  - Wills ST
AD  - Palatin Technologies, Inc., Cranbury, New Jersey, USA.
FAU - Spana, Carl
AU  - Spana C
AD  - Palatin Technologies, Inc., Cranbury, New Jersey, USA.
LA  - eng
SI  - ClinicalTrials.gov/NCT04268069
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20230907
PL  - United States
TA  - J Ocul Pharmacol Ther
JT  - Journal of ocular pharmacology and therapeutics : the official journal of the 
      Association for Ocular Pharmacology and Therapeutics
JID - 9511091
RN  - 0 (Ophthalmic Solutions)
RN  - TPY09G7XIR (Fluorescein)
SB  - IM
MH  - Humans
MH  - Ophthalmic Solutions/adverse effects
MH  - Treatment Outcome
MH  - Fluorescein
MH  - *Dry Eye Syndromes/drug therapy/diagnosis
MH  - Cornea
MH  - Double-Blind Method
MH  - Tears
PMC - PMC10654643
OTO - NOTNLM
OT  - PL9643
OT  - conjunctival staining
OT  - dry eye disease
OT  - efficacy
OT  - melanocortin receptor agonist
OT  - tear film breakup time
COIS- D.E. received financial support from Alcon, Allergan, AxeroVision, Bausch + Lomb, 
      Hovione, Kala, Novaliq, Novartis, Ocular Therapeutix, and Vistakon. K.K. was an 
      independent contractor at Ora, Inc., throughout the duration of the study. G.O. 
      and M.W. were employees of Ora, Inc., throughout the duration of the study. G.T. 
      received financial support from Mitotech, Kowa, Aldeyra, Topivert, Brim, Palatin, 
      Oyster Point, Allergan, Aerie, Aurinia, ReGenTree, Novaliq, HanAll, and Ora, Inc. 
      P.V. has nothing to disclose. E.B.M. received financial support from Allergan, 
      Aldeyra, Aurinia, HanAll, Mallinckrodt, Mitotech, Nicox, Novaliq, Orasis, Ocular 
      Therapeutix, Palatin, ReGenTree, Santen, and Topivert. J.W., J.D., R.J., S.T.W., 
      and C.S. are employees of Palatin Technologies, Inc.
EDAT- 2023/09/07 18:42
MHDA- 2023/11/06 06:41
PMCR- 2023/11/02
CRDT- 2023/09/07 14:23
PHST- 2023/11/06 06:41 [medline]
PHST- 2023/09/07 18:42 [pubmed]
PHST- 2023/09/07 14:23 [entrez]
PHST- 2023/11/02 00:00 [pmc-release]
AID - 10.1089/jop.2023.0056 [pii]
AID - 10.1089/jop.2023.0056 [doi]
PST - ppublish
SO  - J Ocul Pharmacol Ther. 2023 Nov;39(9):600-610. doi: 10.1089/jop.2023.0056. Epub 
      2023 Sep 7.