On August 1st RXi Pharmaceuticals (NASDAQ:RXII) issued a press release announcing positive results from their RXI-109-1501 Phase I/II trial for retinal scarring. The primary outcome for the trial was to determine the safety of RXI-109 and to measure the pharmacokinetic profile of the drug in blood. A secondary objective was to measure efficacy of RXI-109 employing a variety of measures. These included change from baseline in subretinal fibrosis lesion size, measure of best corrected visual acuity (BCVA) and relative change of connective tissue growth factor (CTGF) in aqueous fluid compared to baseline.
The safety endpoint was met in the trial. There were a total of 25 adverse events, but the majority were mild and the remaining seven were moderate. No dose limiting toxicities or serious toxicities were observed. Based on the assessment of the investigator, none of the adverse events were related to RXI-109 and five were related to the administration procedure.
More specifically, the safety assessment found no instances of:
‣ clinically significant ocular inflammation (such as 3+ aqueous and vitreous cells)
‣ retinal toxicities (such as moderate or severe retinal hemorrhages)
‣ reduction from baseline BCVA ≥30 letters using ETDRS visual acuity charts
‣ drug related adverse events above Grade 3 or sustained intraocular pressure ≥30 mmHg
The efficacy outcomes were favorable and all but one enrollee showed an improvement in best corrected visual acuity (BCVA) using ETDRS. The one individual that experienced deterioration on this metric was in the low dose cohort. Below we summarize the BCVA score by cohort.
View Exhibit I – RXI-109 Retinal Scarring Results
Subretinal fibrosis lesion size was measured by spectral domain optical coherence tomography. The overall measured reduction in the study was -6.9% with a range of -14.8% to +3.6%. Below we summarize the dose dependent reduction in lesion size by cohort.
View Exhibit II – Central Lesion Thickness Change
Despite being a small study, the outcome was positive. Safety was confirmed and there was a dose dependent response in the nine patients who participated in the trial.
Study 1501 – RXI-109 / Retinal Scarring Trial Design
Study 1501 was a Phase I/II assessment designed as a multi-dose, dose escalation study conducted in subjects with AMD with evidence of subretinal fibrosis. The study was divided into three equal cohorts with low, intermediate and high dose of RXI-109 administered. Each of the 9 subjects enrolled received four doses of RXI-109 by intraocular injection at one month intervals for a total dosing period of three months. The study began in November 2015 and topline results were announced August 2018. Primary endpoints for the study include an assessment of the incidence and severity of adverse events and determination of peak whole blood concentration (Cmax), area under the whole blood concentration versus time curve (AUC) and drug half-life in whole blood (T1/2). The secondary endpoint is an evaluation of the ability of RXI-109 to reduce the formation or progression of subretinal fibrosis.
View Exhibit III – Early Treatment Diabetic Retinopathy Study (ETDRS) Acuity Charts (Source: Precision Vision)
Additional Development of RXI-109 for Retinal Scarring
RXi plans to partner further development of RXI-109. It is expected that a Phase IIb trial will be necessary for the retinal scarring programs requiring multiple hundreds of observations from a safety perspective. This will be directed and funded by a partner. Now that results are available, potential suitors have the information needed to move forward. During 2018 to date, RXi has met with several potential suitors who are familiar with the programs and we expect that a decision will be made before year end.
Age Related Macular Degeneration (Retinal Scarring) Refresher
There are two types of age related macular degeneration (AMD), dry and wet. The dry type, or non-exudative, non-neovascular type is thought to result from the effects of aging and the thinning of macular tissues and depositing of pigment in the macula. Wet AMD is usually more severe and arises from the formation of new blood vessels that grow beneath the retina and leak blood and fluid. The extravasation of fluid from the eye can cause damage to retinal cells resulting in spot blindness. About 10% of the total AMD population suffers from the wet version.
We see a global addressable market of just under 3 million persons today growing at a 2% annual rate. Our model forecasts this population to be over a third penetrated by RXI-109 as there are no alternative therapies.
The results for the RXI-109 Retinal Scarring study were very favorable. Safety was a strong point with no severe adverse events and only Grade I or II adverse events mostly related to administration. Regarding efficacy, fibrous lesions and visual function were both improved compared to baseline in the treated eye. Anti-VEGF treatments for blood vessel growth in the eye were approved based on a standard of avoiding deterioration in vision, rather than improvement. Therefore, the dose dependent improvement in response to RXI-109 is a strong argument for its efficacy if this same standard is applied. While the trial only enrolled nine patients, we interpret the results as strongly supportive of an expanded Phase IIb study. With no other therapies available to treat retinal scarring, RXI-109 is a validated attractive asset that can can provide non-dilutive capital to RXi when sold or partnered.
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