Protein agent may change approach to treating dry eye, inflammation

Reviewed by Paul Karpecki, OD

Take-home: Recombinant human lubricin showed potential as a new therapeutic approach to the management of dry eye disease in a small clinical trial. Compared with sodium hyaluronate, lubricin (Lubris BioPharma), significantly improved both signs and symptoms of moderate dry eye after two weeks of treatment.

Patients with moderate dry eye disease experienced significant improvement in signs and symptoms following a two-week clinical trial of a recombinant version of the human protein lubricin (Lubris BioPharma) compared to sodium hyaluronate (HA).

Although lubricin is still an investigational agent, it shows promise as an innovative approach to preventing or reducing ocular inflammation, said Paul Karpecki, OD, an expert on ocular surface disease.

In this randomized, double-masked, parallel group safety and efficacy trial and 1-week follow-up, 19 patients were treated with lubricin 150 µL eye drops and 20 with HA 0.18% eye drops.

Subjects receiving lubricin experienced greater than 70% reduction in their symptoms from baseline. Improvements against HA were reported for foreign body sensation (p < 0.013), sticky feeling (p < 0.0432), blurred vision (p < 0.0013), and photophobia (p < 0.011) in at least one eye.

Improvements shown

Lubricin also demonstrated statistically significant improvements against HA in the following objective signs of dry eye: corneal fluorescein staining (OD/OS: 43.8%, 50.0%, vs. 26.5%, 23.3%, p < 0.0398, p < 0.0232), TFBUT (p < 0.010), eyelid erythema (p < 0.004), conjunctival erythema (p < 0.0013), and daily mean  instillations (p < 0.04). No adverse effects related to lubricin were reported during the trial.

A key point from the trial was the statistical improvement in both signs and symptoms, Dr. Karpecki said, adding that the improvements in corneal staining, symptoms, and visual acuity amount to a “trifecta,” hinting at the potential of lubricin.

Results of the study were published in The Ocular Surface. The study was sponsored by Lubris BioPharma and Dompé Farmaceutici and was conducted at the Policlinico Umberto I, Sapienza University of Rome.

The molecule lubricin is one of the most lubricating and adhesive proteins in the body and is found on the ocular surface. It protects tissue surfaces from friction-related damage and wear, but its production may become impaired due to inflammation.

The hypothesis behind the development of recombinant lubricin is that by reducing friction it could interrupt the inflammatory cascade and help restore proper function in the treated area.

“This is exciting,” said Dr. Karpecki, who is in private practice in Lexington and Louisville, KY. He was not involved in the study. “The new area of interest is going to be proteins.”

Lubricin is one of a number of proteins found in tears and one of the most lubricious, making it an important barrier against ocular surface damage.

Commenting further on the trial findings, he noted that a small study with about 20 patients in each arm would not ordinarily be expected to produce statistically valid outcomes.

“The fact that it did really impress me,” Dr. Karpecki said. “It amazes me that you can get that kind of success with such a small N number, which bodes well for the future of this product.”

Blurred vision outcome

Blurred vision outcome

One finding that stood out was the day 14 outcome for blurred vision, Dr. Karpecki said, explaining that significant improvement often takes longer. In the left eye, lubricin supplementation achieved a 74.4% reduction from baseline compared to 56.3% in the HA group. However, it will be important to assess the efficacy of lubricin over longer periods in future studies.

The study design in which lubricin was compared with HA is also highly relevant, he said. HA is the most prescribed treatment for dry eye in most countries, although not in the United States.

“That in itself is fairly bold, to say we’re going to go up against number one and see if we can be equal,” he said. “In this case, they were far superior, and especially with a relatively small number of patients in each group.”

Paul Karpecki, OD

E: paul@karpecki.com

Dr. Karpecki is a consultant to Lubris BioPharma.