Palatin pummelled as dry eye therapy underwhelms in phase 3

Palatin Technologies’ therapy for dry eye disease (DED) missed its primary endpoints in a phase 3 trial, knocking investor confidence as it tries to chart a way forward.

The MELODY-1 study of melanocortin agonist PL9643 failed to show statistical significance on two co-primary endpoints of a symptom (pain) and sign (conjunctival lissamine green staining) of DED, so Palatin has turned to a subgroup analysis to try to keep the programme going.

The company said that significant improvements in pain and various secondary endpoints were seen in female patients and those aged 60 or over and would be discussed with the FDA to see if there is a path to approval with a second pivotal trial. It also pointed to a high response to the control therapy, the ophthalmic solution used in the drug without the active ingredient.

Investors seemed unconvinced by the assurances, however, and shares in the company fell by more than a third (38%) in the wake of the announcement, likely in part because the company has been looking for a partner to take PL9643 forward and that could now become more difficult.

Analyst Michael Higgins at Ladenburg Thalman said, however, that the mixed results were “not unlike other DED phase 3s” and showed proof-of-concept in older subjects and women, noting that the study had been especially designed to look at specific patient groups.

“Investors should appreciate that several approved DED treatments have missed the topline efficacy endpoints, but gone on to gain approval,” he wrote in a research note.

That has not always been the case, though. In December, the FDA turned down Aldeyra’s rebroxalap, which also struggled to show efficacy in pivotal trials, saying that the clinical evidence was not adequate to support approval.

“Should PL9643 hit on efficacy measures outside of >60 and women in additional phase 3s, we believe the agency would not limit PL9643 to those demographics in the label,” said Higgins. The FDA requires at least one pivotal, with at least one sign and one symptom improvement for approval.

Palatin is now hoping to meet with the FDA to discuss the data in the second quarter, and Higgins acknowledged that “any partnership would follow the Q2 FDA meeting and be less favourable to Palatin than [...] expected before these results.”

DED is a common inflammatory disease estimated to affect around 38 million adults in the US and causes pain, inflammation, and discomfort. In severe cases, it can lead to permanent visual impairment.

Current therapies like Bausch + Lomb’s Xiidra (lifitegrast) and AbbVie’s Restasis (cyclosporine) are acknowledged to lack efficacy and have side effect problems, but have nevertheless achieved solid sales. Xiidra made around $500 million last year, while former blockbuster Restasis brought in $436 million after a steep decline caused by the start of generic competition.

Bausch + Lomb also claimed FDA approval last year for Miebo (perfluorohexyloctane), which is described as the only FDA-approved treatment for DED that directly targets tear evaporation and which met both primary sign and symptom efficacy endpoints in pivotal trials.

Photo by Fa Barboza on Unsplash