Disappointing clinical trial results have caused two companies to halt development of once-promising drug programs in age-related macular degeneration—squalamine topical solution for treatment of wet AMD and the intravitreal antigen-binding agent lampalizumab for geographic atrophy in AMD.

Ohr Chief Executive Officer Jason Slakter, MD, disclosed the decision to scrap the squalamine program during an announcement of the company’s 2017 finan


cial results. 

In January, the company announced that top-line results of the MAKO trial failed to reach its endpoints. The multicenter, randomized, double-masked trial evaluate

d combination therapy of squalamine b.i.d. in combination with monthly ranibizumab (Lucentis, Roche/Genentech) injections and topical placebo b.i.d with monthly ranibizumab injections. At the time, Dr. Slakter said Ohr was “very disappointed” with the results of the MAKO trial. 

Those on squalamine combination therapy (n=119) achieved a mean gain of 8.33 letters from baseline vs. 10.58 letters from baseline in the placebo-ranibizumab (n=118) group. 

“Based on these results, we have discontinued development of squalamine, taken measures to preserve cash and are evaluating strategic alternatives to maximize shareholder value,” Dr. Slakter says. 

Ohr has engaged Roth Capital Markets to advise the company going forward. 

Lampalizumab is an antigen-binding fragment (Fab) of a humanized, monoclonal antibody directed against complement factor D, a rate-limiting enzyme in the activation and amplification of the alternative complement pathway, dysfunction of which has been linked to the pathogenesis of AMD.

Disappointing results from two Phase III trials, SPECTRI and CHROMA, apparently doomed the lampalizumab program. Roche reported last September that the SPECTRI trial showed the drug did not reduce mean change in GA lesion area compared to sham treatment at 48 weeks. 

At the time, Roche decided to suspend further dosing in SPECTRI study participants until it could evaluate results from CHROMA, the second Phase III trial. 

At a review of Roche’s 2017 results in London in February, Roche CEO Severin Schwan disclosed the company was removing lampalizumab for GA, also known as RG7417, from Phase III trials. The drug has also been removed from Roche’s online product development portfolio. 

The financial analytics firm Jefferies had projected lampalizumab would achieve $2 billion in yearly sales for Roche.

Could Müller Glia Cells be a New Treatment Target in AMD? 

Researchers at Duke University may have identified a potential new treatment target in macular degeneration. Early stage research has shown that injection of human umbilical stem cells, or hUTC, into the retina may help preserve and restore vision in macular degeneration, although the underlying mechanisms behind the therapy remain unknown.

The findings, published online in the Journal of Neuroscience, show that hUTC treatment preserves the function of Müller glia cells in rats with degenerative vision loss.1 “This provides strong evidence that Müller glia are important therapeutic targets for treating degenerative eye diseases,” says lead study author Sehwon Koh, PhD. 

The Duke scientists first examined the retinas of young rats that were genetically predisposed to an eye disease similar to retinitis pigmentosa in humans. They found that the neural synapses within the retina began to deteriorate even before the photoreceptors started to die.

As the number of neural synapses declined, the Müller glia also deteriorated, pulling their branches away from neurons and dividing haphazardly. When the researchers injected hUTC behind the retinas of the rats, the Müller glia remained healthy, as did the neural synapses. The treatment succeeded in preserving the majority of the rats’ vision and stopped the photoreceptors from dying.

“Previous studies primarily focused on neurons and the retinal pigment epithelium cells as culprits in degeneration,” says Cagla
Eroglu, PhD, an associate professor of cell biology and neurobiology at Duke University Medical Center whose laboratory is conducting the research. 

“Müller glia were not considered an important player in the early stages of retinal degeneration and were not thought to be an important target for hUTC treatment, but our findings suggested otherwise,” Dr. Eroglu says.

To test whether the Müller glia were truly the key players in the synaptic loss, the team used gene editing to remove a specific gene from Müller glia cells. Deleting this gene is known to cause retinal degeneration, but its function in Müller glia has never been explored.

Without this gene, the Müller glia were defective and bore striking similarities to those in rats that had developed RP. In addition, the neural connections within retinas of these rats were malformed, mimicking the problems seen in early stages of retinal degeneration.

“What we are seeing here is that Müller glia are important players in retinal health,” Dr. Eroglu says. “They are impaired in disease, and effective cellular therapies should target not only other retinal cell types but these cells as well.”

The research was carried out in collaboration with Janssen Research & Development and supported by grants from the National Institutes of Health and other organizations.  RS


1. Koh S, Chen WJ, Dejneka NS, et al. Subretinal human umbilical tissue-derived cell transplantation preserves retinal synaptic connectivity and attenuates Müller glial reactivity. J Neuroscience. Published online February 5, 1018. DOI: 10.1523/JNEUROSCI.1532-17.2018