FREMONT, CA, USA I June 25, 2014 I Quark Pharmaceuticals, Inc. today announced that the first patient has been dosed in a double-masked, randomized sham controlled Phase IIa safety, tolerability and pharmacokinetics study of Quark’s proprietary neuroprotective agent QPI-1007 when administered by single intravitreal (IVT) injection in patients suffering an acute attack of primary angle closure glaucoma (PACG). QPI-1007 is a siRNA designed to temporarily inhibit the expression of Caspase 2, a protein that has been shown to play a role in retinal ganglion cell (RGC) cell death. QPI-1007 is currently under investigation for the treatment of non-arteritic ischemic optic neuropathy (NAION). In a Phase I/IIa multicenter clinical study recently completed in the USA and Israel a single intravitreal injection of QPI-1007 resulted in a neuroprotective effect in NAION patients.
The study is a double-masked, single dose, randomized sham controlled study of QPI-1007 conducted in several centers in the United States, Vietnam, and Singapore. Approximately 60 patients with unilateral acute PACG (APACG) will be randomized at a 1:1 ratio to receive 1.5 mg IVT injection of QPI-1007 (active group) or sham injection (control group). Once the acute attack has been treated by standard of care methods (medical therapy and laser iridotomy) and the intraocular pressure in the study eye becomes less than 25 mmHg, subjects will be randomized into the study within 120 hours of the attack. Randomization will be stratified by time from symptom onset to the study drug administration or sham procedure ( 72 hours). The primary objective of the study is to evaluate the safety, tolerability and pharmacokinetics of QPI-1007 in subjects with acute primary angle-closure glaucoma. In addition, the biological activity of the drug will be studied by comparing the active group and control group study eyes at Month 4 with respect to a series of visual function parameters.
“We are delighted to announce that patient dosing has begun in the Phase I/IIa trial of QPI-1007 in patients with acute angle closure glaucoma,” said Dr. Daniel Zurr, CEO of Quark. “Acute attacks of angle closure glaucoma are potentially associated with significant ocular morbidity and may lead to permanent vision loss from ocular ischemia and consequent RGC death. The ability to protect ganglion cells from cell death could represent a breakthrough in the effort to save the vision of patients who suffer acute angle closure glaucoma attacks and in the broader area of neuroprotection. With its unique properties, we believe that QPI-1007 is a potential game changer in the future treatment of all glaucoma patients.”
About QPI-1007
QPI-1007 is an investigational chemically modified siRNA drug designed to temporarily inhibit the expression of Caspase 2 developed by Quark based on entirely internally developed intellectual property of Quark. Intravitreal administration of QPI-1007 in rat models of optic nerve crush and axotomy as well as in acute retinal ischemia achieved by acute transient elevation of the intraocular pressure had ocular neuroprotective effects.
In the Phase I/IIa study in patients with NAION, an intravitreal injection of QPI-1007 was well tolerated. There were no reported serious adverse events, no dose limiting toxicities and no discontinuations due to adverse events. The study was not designed for determining the efficacy of the drug, however, best-corrected visual acuity (BCVA) was compared to historical control. The proportion of NAION patients improving by >= 3 lines (>= 15 letters) at month 3 was 51.7% (n=29) compared with 39.7% (n=121) of IONDT historical controls [The IONDT Research Group (1995). JAMA, Vol.273, pp.625 — 632]. None of the NAION patients lost three or two lines (and only 1 patient lost 1 line only) of VA at months 3 and 6 compared with 9.1% and, 14.8% respectively, in the historical controls. One patient (3.6% of patients) with QPI-1007 treatment lost >= 3 lines of VA at 12 months. This was the first proof of concept in human for this unmet medical need.
About Acute Angle Closure Glaucoma
Acute angle-closure glaucoma represents an ocular emergency, in which the outflow of aqueous humor through the anterior chamber angle is blocked. As a result, intra-ocular pressure (IOP) rises to levels high above the normal, causing pain, hyperemia, corneal epithelium edema, iris ischemia and ocular tissue damage including damage to the lens, and increased risk of ischemic damage to the neurosensory retina and the optic nerve. The high IOP during the acute attack was found to cause progressive long-term damage and structural and functional changes to the retina. Contributing to this damage is likely to be ischemic injury sustained RGCs during the attack. Some cells may not survive the acute attack, while other cells initiate apoptotic cascade. The visual morbidity from APACC is significant. The natural history in untreated patients is progressive vision loss that may result in unilateral or bilateral blindness. It is estimated that all forms of PACG account for about 10% of glaucoma cases in the U.S., but in 35% up to 50% of glaucoma cases in Asian populations. Acute attacks of ACG seem to occur in 20%-40% of PACG.
About Quark Pharmaceuticals, Inc.
Quark Pharmaceuticals, Inc., the world leader in novel therapeutic RNAi discovery and development, has the largest clinical-stage siRNA pipeline in the industry. The Company’s fully integrated drug development platform spans therapeutic target identification to drug development. Quark’s approach to delivery allows targeting of tissues and organs including the eye, kidney, ear, lung, skin, spinal cord and brain. Quark has three siRNA product candidates in clinical development in five different disease indications of which four are in Phase II. Quark’s Joint venture in China, Kunshan Ribo-Quark Pharmaceutical Inc, and its strategic partner in India, Biocon Limited, are part of Quark’s world wide clinical studies network.
Quark is headquartered in Fremont, California and operates research and development facilities in Boulder, Colorado and Ness-Ziona, Israel. For additional information please visit: www.quarkpharma.com.
SOURCE: Quark Pharmaceuticals
Post Views: 683
FREMONT, CA, USA I June 25, 2014 I Quark Pharmaceuticals, Inc. today announced that the first patient has been dosed in a double-masked, randomized sham controlled Phase IIa safety, tolerability and pharmacokinetics study of Quark’s proprietary neuroprotective agent QPI-1007 when administered by single intravitreal (IVT) injection in patients suffering an acute attack of primary angle closure glaucoma (PACG). QPI-1007 is a siRNA designed to temporarily inhibit the expression of Caspase 2, a protein that has been shown to play a role in retinal ganglion cell (RGC) cell death. QPI-1007 is currently under investigation for the treatment of non-arteritic ischemic optic neuropathy (NAION). In a Phase I/IIa multicenter clinical study recently completed in the USA and Israel a single intravitreal injection of QPI-1007 resulted in a neuroprotective effect in NAION patients.
The study is a double-masked, single dose, randomized sham controlled study of QPI-1007 conducted in several centers in the United States, Vietnam, and Singapore. Approximately 60 patients with unilateral acute PACG (APACG) will be randomized at a 1:1 ratio to receive 1.5 mg IVT injection of QPI-1007 (active group) or sham injection (control group). Once the acute attack has been treated by standard of care methods (medical therapy and laser iridotomy) and the intraocular pressure in the study eye becomes less than 25 mmHg, subjects will be randomized into the study within 120 hours of the attack. Randomization will be stratified by time from symptom onset to the study drug administration or sham procedure ( 72 hours). The primary objective of the study is to evaluate the safety, tolerability and pharmacokinetics of QPI-1007 in subjects with acute primary angle-closure glaucoma. In addition, the biological activity of the drug will be studied by comparing the active group and control group study eyes at Month 4 with respect to a series of visual function parameters.
“We are delighted to announce that patient dosing has begun in the Phase I/IIa trial of QPI-1007 in patients with acute angle closure glaucoma,” said Dr. Daniel Zurr, CEO of Quark. “Acute attacks of angle closure glaucoma are potentially associated with significant ocular morbidity and may lead to permanent vision loss from ocular ischemia and consequent RGC death. The ability to protect ganglion cells from cell death could represent a breakthrough in the effort to save the vision of patients who suffer acute angle closure glaucoma attacks and in the broader area of neuroprotection. With its unique properties, we believe that QPI-1007 is a potential game changer in the future treatment of all glaucoma patients.”
About QPI-1007
QPI-1007 is an investigational chemically modified siRNA drug designed to temporarily inhibit the expression of Caspase 2 developed by Quark based on entirely internally developed intellectual property of Quark. Intravitreal administration of QPI-1007 in rat models of optic nerve crush and axotomy as well as in acute retinal ischemia achieved by acute transient elevation of the intraocular pressure had ocular neuroprotective effects.
In the Phase I/IIa study in patients with NAION, an intravitreal injection of QPI-1007 was well tolerated. There were no reported serious adverse events, no dose limiting toxicities and no discontinuations due to adverse events. The study was not designed for determining the efficacy of the drug, however, best-corrected visual acuity (BCVA) was compared to historical control. The proportion of NAION patients improving by >= 3 lines (>= 15 letters) at month 3 was 51.7% (n=29) compared with 39.7% (n=121) of IONDT historical controls [The IONDT Research Group (1995). JAMA, Vol.273, pp.625 — 632]. None of the NAION patients lost three or two lines (and only 1 patient lost 1 line only) of VA at months 3 and 6 compared with 9.1% and, 14.8% respectively, in the historical controls. One patient (3.6% of patients) with QPI-1007 treatment lost >= 3 lines of VA at 12 months. This was the first proof of concept in human for this unmet medical need.
About Acute Angle Closure Glaucoma
Acute angle-closure glaucoma represents an ocular emergency, in which the outflow of aqueous humor through the anterior chamber angle is blocked. As a result, intra-ocular pressure (IOP) rises to levels high above the normal, causing pain, hyperemia, corneal epithelium edema, iris ischemia and ocular tissue damage including damage to the lens, and increased risk of ischemic damage to the neurosensory retina and the optic nerve. The high IOP during the acute attack was found to cause progressive long-term damage and structural and functional changes to the retina. Contributing to this damage is likely to be ischemic injury sustained RGCs during the attack. Some cells may not survive the acute attack, while other cells initiate apoptotic cascade. The visual morbidity from APACC is significant. The natural history in untreated patients is progressive vision loss that may result in unilateral or bilateral blindness. It is estimated that all forms of PACG account for about 10% of glaucoma cases in the U.S., but in 35% up to 50% of glaucoma cases in Asian populations. Acute attacks of ACG seem to occur in 20%-40% of PACG.
About Quark Pharmaceuticals, Inc.
Quark Pharmaceuticals, Inc., the world leader in novel therapeutic RNAi discovery and development, has the largest clinical-stage siRNA pipeline in the industry. The Company’s fully integrated drug development platform spans therapeutic target identification to drug development. Quark’s approach to delivery allows targeting of tissues and organs including the eye, kidney, ear, lung, skin, spinal cord and brain. Quark has three siRNA product candidates in clinical development in five different disease indications of which four are in Phase II. Quark’s Joint venture in China, Kunshan Ribo-Quark Pharmaceutical Inc, and its strategic partner in India, Biocon Limited, are part of Quark’s world wide clinical studies network.
Quark is headquartered in Fremont, California and operates research and development facilities in Boulder, Colorado and Ness-Ziona, Israel. For additional information please visit: www.quarkpharma.com.
SOURCE: Quark Pharmaceuticals
Post Views: 683
