RXi Pharmaceuticals Announces Positive Results From Phase 1/2 Trial With RXI-109 For Retinal Scarring
The primary objective was met as shown by the absence of dose-limiting and serious toxicities, and only mild to moderate procedure related adverse events. None of the adverse events were drug related. In addition, comprehensive ocular examinations showed no indications of inflammation nor any other tolerability issues related to the treatment. Therefore, these study results show that RXI-109 was safe and well tolerated for all patients included in the three dosage groups.
Even though the primary objective of this study was to evaluate the safety and tolerability of ocular injections with RXI-109, several assessments were included to measure a potential clinical effect. These assessments included measuring the change from baseline in subretinal fibrosis lesion size, as measured by spectral domain (SD) optical coherence tomography (OCT), fundus photography and fluorescein angiography, as well as a potential effect on visual function by measuring the best corrected visual acuity (BCVA), i.e. the best vision a patient could achieve with correction (such as glasses), as measured on the standard eye charts.
RXi's Chief Development Officer,
About the RXI-109-1501 Study
RXI-109-1501 is a multi-center, multi-dose, dose escalation trial conducted in subjects with advanced neovascular or 'wet' age-related macular degeneration and accompanying subretinal fibrosis. It is the first clinical study (phase 1/2 trial) on the use of RXI-109 by ocular injections. Per the protocol, three dose levels were evaluated in a small number of subjects in order to establish safety information and to help determine the dosing regimen for a future Phase 2 study. Nine subjects were enrolled, three in each of the following dosage groups: Cohort 1 (low dose), Cohort 2 (intermediate dose), Cohort 3 (high dose). Each subject received a total of four doses of RXI-109 at one-month intervals. RXI-109 was administered by intravitreal injection in one eye only. The dosing period (3 months) was followed by a four-month observation period.
Overall Safety and Tolerability Results
- There were no instances of Dose Limiting Toxicities or Serious Toxicities throughout the study. In other words, there were 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, drug related adverse events with a CTCAE grade of 3 or higher or sustained intraocular pressure ≥30 mmHg.
- In total twenty-five AEs were reported, thirteen in Cohort 1, seven in Cohort 2 and five in Cohort 3. The severity of all these AEs was either mild or moderate: Eighteen of these AEs were considered mild and the other seven AEs were considered moderate. Of the twenty-five AEs, none were related to the study drug, and eight AEs occurring in five subjects were deemed related to the study procedures (i.e. the intra-ocular injections).
- There were no negative clinically significant changes in physical examination findings, ocular examinations and assessments, and clinical laboratory results that were deemed related to the study drug.
- Compared to the baseline visit, all but one subject had an improved BCVA of the study eye at the last follow up visit. One subject (Cohort 1) had a lower score compared to baseline. The average increase in BCVA was +2.3 for Cohort 1, +3.7 for Cohort 2 and +10.0 for Cohort 3. The median change from baseline BCVA was 32.0% for the study eye and 4.9% for the contralateral eye.
- The various imaging modalities and image analysis techniques used, suggest a halt or even reversal of the disease progression in the study eye of several subjects. For example, at the last follow-up visit the mean central lesion thickness change compared to baseline (as measured by OCT) was -6.9%, with a range of -14.8% to +3.6%. The largest change was again seen in Cohort 3 (mean reduction of -10.2%) followed by Cohort 2 (mean reduction of -6.7%) and Cohort 1 (mean reduction of -3.8%).
- A criterium for patient "success" was not predefined in this study, but if the same criteria would be applied in this study as in pivotal trials with anti-VEGF treatments1 (i.e. "maintaining vision" defined as losing fewer than 15 letters in BVCA tests at 52 weeks), treatment success would be declared in all but one patient.
About Advanced Neovascular Age-related Macular Degeneration, and Retinal Scarring
About RXi's Ophthalmology Franchise
RXI-109 and RXi's sd-rxRNA technology platform are broadly protected in
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This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Forward-looking statements are neither historical facts nor assurances of future performance. These statements are based only on our current beliefs, expectations and assumptions regarding the future of our business, future plans and strategies, projections, anticipated events and trends, the economy and other future conditions. Because forward-looking statements relate to the future, they are subject to inherent uncertainties, risks and changes in circumstances that are difficult to predict and many of which are outside of our control. Our actual results may differ materially from those indicated in the forward-looking statements as a result of a number of important factors, including the safety and efficacy of our product candidates, future success of our clinical trials and scientific studies, our ability to enter into strategic partnerships and the future success of these strategic partnerships, the availability of funds and resources to pursue our research and development projects and general economic conditions. Our Annual Report on Form 10-K and subsequent Quarterly Reports on Form 10-Q include detailed risks under the caption "Risk Factors" that may affect our business, results of operations and financial condition. Readers are urged to review these risk factors and to not act in reliance on any forward-looking statements, as actual results may differ from those contemplated by our forward-looking statements. RXi does not undertake to update forward-looking statements to reflect a change in its views, events or circumstances that occur after the date of this release.
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1 Lucentis – full prescribing information: https://www.gene.com/download/pdf/lucentis_prescribing.pdf
Eylea – full prescribing information: https://www.regeneron.com/sites/default/files/EYLEA_FPI.pdf