MARLBOROUGH, Mass.,
Aug. 1, 2018 /PRNewswire/ -- RXi
Pharmaceuticals Corporation (NASDAQ: RXII) a biotechnology company
developing the next generation of immuno-oncology therapeutics
based on its proprietary self-delivering RNAi (sd-rxRNA)
therapeutic platform, today announced positive results with RXI-109
in a Phase 1/2 clinical trial. RXI-109-1501 is an open-label,
multi-dose, dose escalation study with three dose cohorts, enrolled
sequentially, evaluating the safety and tolerability of RXI-109
injections in the eye of subjects with advanced neovascular
age-related macular degeneration (NVAMD), and accompanying
subretinal fibrosis. During this study, the clinical effect of
these injections was evaluated as a secondary endpoint.
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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, Gerrit
Dispersyn, Dr. Med. Sc., commented: "This study is exciting
on several levels. First, the impressive safety and tolerability of
intravitreal injections of RXI-109 and the promising clinical data,
support further development of this compound in retinal scarring.
In addition, these positive findings also open significant avenues
for the use of our platform technology in ophthalmology, with
sd-rxRNA targeting other proteins for other ocular indications.
Also, the results contribute to an already extensive set of data
that RXI-109, by preventing the overexpression of connective tissue
growth factor, can result in a positive impact in various
indications where excessive fibrosis is seen. Even though this is a
small study, it is encouraging that some of the summary statistics
on ocular assessments performed in the study eye at the last
follow-up visit, suggest a more pronounced change over
baseline in the highest dose group (Cohort 3), compared to other
groups."
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.
Clinical activity
- 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
In the United States, there is
no FDA-approved targeted therapy for the treatment and prevention
of subretinal scarring in advanced wet age-related macular
degeneration. This presents a large unmet market opportunity
with approximately 11M Americans have
some form of AMD, while 1.1M have
NVAMD. We believe that RXI-109 is an excellent
candidate to help patients with advanced NVAMD to reduce the
progression of subretinal fibrosis, or as a potential prophylactic
treatment for early stage NVAMD patients prior to the development
of subretinal fibrosis.
About RXi's Ophthalmology Franchise
RXI-109 and RXi's sd-rxRNA technology platform are broadly
protected in the United States and
International regions. The Company's robust patent estate
provides for multiple commercial and business development
opportunities.
RXi announced in January 2018 that
it would exclusively focus on developing the next generation of
immuno-oncology therapeutics based on its self-delivering RNAi
therapeutic platform. As such, it is actively seeking to
partner or out-license both its Dermatology and Ophthalmology
Franchises.
Each of these Franchises is comprised of a number of preclinical
and clinical-stage assets broadly covered by a robust intellectual
property estate. To obtain more information about these assets,
contact RXi's Vice President of Business Operations, Dr.
James Cardia at
jcardia@rxipharma.com.
About RXi Pharmaceuticals
RXi Pharmaceuticals Corporation (NASDAQ: RXII) is a
biotechnology company developing the next generation of
immuno-oncology therapeutics based on its self-delivering RNAi
(sd-rxRNA®) therapeutic platform. The Company's discovery and
research efforts are focused on developing sd-rxRNA therapeutic
compounds to be used with an Adoptive Cell Transfer (ACT) approach.
This process uses immune cells, such as T-lymphocytes that are
isolated from the patient or retrieved from allogeneic immune cell
banks, and then expanded and in some cases processed to express
tumor-binding receptors. Our approach introduces a new and
important step in ex-vivo processing of the immune cells where
sd-rxRNA is used to eliminate the expression of immunosuppressive
receptors or proteins from the therapeutic immune cells, making
them less sensitive to tumor resistance mechanisms and thus
improving their ability to destroy the tumor cells. Essentially, we
aim to maximize the power of our sd-rxRNA therapeutic compounds by
weaponizing therapeutic immune effector cells to attack cancer and
ultimately provide patients battling terminal cancers with a
powerful new treatment option that goes beyond current treatment
modalities.
For additional information, visit the Company's website,
www.rxipharma.com.
Forward-Looking Statements
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.
Contact RXi Pharmaceuticals
Corporation
Tamara
McGrillen
Tel: +1 508-929-3646
Email: tmcgrillen@rxipharma.com
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
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