OSD Overhaul
Three new pipeline therapies may offer relief to patients with ocular surface disease
It’s estimated that there are nearly 100 million people worldwide who have some form of dry eye disease (DED). However, most people with DED go undiagnosed, and for those who do receive a diagnosis, the most commonly offered treatment is artificial tears. This might be about to change. We review three of the latest developments in the DED therapy pipeline.
Early-phase trials: rhNGF
Neurotrophic keratitis (NK) is a rare degenerative disease in which trigeminal nerve function – and therefore corneal sensation – is impaired (1). As a result of this lack of sensation, metabolism and mitosis in the corneal epithelium occur at a reduced rate and, eventually, corneal epithelial cells show damage and the cornea begins to thin. Although there are ways to alleviate the symptoms of the disease, what’s really needed is a treatment for its root cause – and the European Medicines Agency (EMA) has just granted recombinant human nerve growth factor (rhNGF) orphan drug status to treat neurotrophic keratitis (2). rhNGF was recently the subject of the REPARO Phase I/II trial (NCT01756456) which evaluated its safety and efficacy in patients with stage 2 and 3 NK; preliminary results presented at EUCORNEA last year indicate that corneal healing occurred in more than 70 percent of patients after eight weeks, with reductions in lesion size and symptom improvements also being observed. The link with DED? NK can present in patients with severe DED, and the same underlying pathologies can underpin both disease states.
Phase III trials: tavilermide
The nerve growth factor story continues – tavilermide (Mimetogen Pharmaceuticals/Allergan), a small molecule, NGF peptidomemtic, which functions as a TrkA receptor partial agonist and acts to induce mucin production has recently commenced a Phase III trial (NCT02634853), billed as a double-blind, randomized, placebo-controlled evaluation of twice-daily 1% tavilermide ophthalmic solution (vs. vehicle control) for the treatment of keratoconjunctivitis sicca (KS), and has an estimated enrolment of 400 patients. Primary outcome measures are corneal fluorescein staining (CFS) and ocular discomfort at day 57 of the trial.
Interestingly, this trial mirrors the previous tavilermide Phase III trial (NCT01960010) that compared the same drug dose and regimen as the newer trial against vehicle control in patients with “dry eye syndromes” (rather than KS), but had slightly different primary outcome measures of CFS and ocular dryness at days 29 and 28, respectively. Topline results from the earlier trial (published in a press release) declared “significant improvements in both signs and symptoms with 1% tavilermide vs. placebo”, together with “strong safety, comfort and tolerability profiles” (3).
Preclinical research: Oculeve OD-01
Allergan made quite a few headlines in 2015 (and it looks like they will continue to do so in 2016 [4]). But last July, a headline informed us that “Allergan [was] to Acquire Oculeve Dry Eye Disease Development Programs.” Why? Because of Oculeve’s promising device in development, OD-01. It's a non-invasive, nasal neurostimulation device that stimulates the lacrimal gland to produce more tears. One recently published study (5) suggests that the device could be made more effective than originally intended, just by changing where the device is placed. Stanford University-based researchers found that electrical stimulation of the lacrimal gland and afferent nerves in rabbits increased tear generation by over 50 percent, but when the Oculeve device was implanted beneath the inferior lacrimal gland, and near the afferent athmoid nerve, they found something quite unexpected.
Daniel Palanker, one of the study’s co-authors explains: “Initially we only planned to stimulate the lacrimal gland. The biggest surprise for us was discovering that stimulating the afferent neural pathway provided a more potent and long-lasting tear response.”
- S Bonini et al., “Neurotrophic keratitis”, Eye (Lond), 17, 989–995 (2003). PMID: 14631406.
- Business Wire, “rhNGF, the Dompé Biotech molecule for the treatment of neurotrophic keratitis, receives orphan drug designation from the European Medicines Agency”, (2015). Available at: bit.ly/1Id3HMj. Accessed December 18, 2015.
- BioSpace, “Mimetogen Pharmaceuticals announces topline results of its second clinical study with MIM-D3 for the treatment of dry eye syndrome”, Available at: bit.ly mimetogen. Accessed January 12, 2015.
- M Schubert, “A turbulent transation”, The Ophthalmologist, 25 (2015). Available at: bit.ly/turbtrans. Accessed January 12, 2016.
- C Orlet, “Allergan inks $50 million licensing deal for Mimetogen’s dry eye treatment”, (2015). Available at: bit.ly/1PcYjKq. Accessed December 18, 2015.
I have an extensive academic background in the life sciences, having studied forensic biology and human medical genetics in my time at Strathclyde and Glasgow Universities. My research, data presentation and bioinformatics skills plus my ‘wet lab’ experience have been a superb grounding for my role as a deputy editor at Texere Publishing. The job allows me to utilize my hard-learned academic skills and experience in my current position within an exciting and contemporary publishing company.
I spent seven years as a medical writer, writing primary and review manuscripts, congress presentations and marketing materials for numerous – and mostly German – pharmaceutical companies. Prior to my adventures in medical communications, I was a Wellcome Trust PhD student at the University of Edinburgh.
