MINNEAPOLIS, MN, USA I July 06, 2022 I DiaMedica Therapeutics Inc. (Nasdaq: DMAC), a clinical-stage biopharmaceutical company focused on developing novel treatments for neurological disorders and kidney diseases, today announced that the U.S. Food and Drug Administration (FDA) has placed a clinical hold on the Company’s Phase 2/3 ReMEDy2 trial studying the use of the Company’s product candidate, DM199, to treat acute ischemic stroke (AIS) patients. The clinical hold was initiated following the Company’s pause in patient enrollment and submission of three serious adverse event reports to the FDA related to clinically significant, transient hypotension (low blood pressure) occurring shortly after initiation of the intravenous (IV) dose of DM199. The blood pressure levels of the three patients recovered back to their baseline blood pressure within minutes after IV infusion was stopped.
The Company believes that the adverse events resulted from switching to an IV bag formulated from different materials in the ReMEDy2 trial compared to the IV bag used in the prior Phase 2 ReMEDy1 trial. Due to supply issues, the type of IV bag used in the ReMEDy1 trial was not available in many U.S. hospitals, and accordingly after routine compatibility testing, a different type of IV bag was selected for use in the ReMEDy2 trial. As part of the Company’s evaluation of the events that lead to these hypotensive events, the Company is confirming the differences in drug absorption in the IV bags used in the ReMEDy1 trial compared to the ReMEDy2 trial and plans to work with the FDA to modify the ReMEDy2 trial protocol to adjust the DM199 IV dosing to more closely match the dosing in the ReMEDy1 trial, taking into account these differences. The Company notes that no such hypotension issues were reported in its ReMEDy1 trial in which 46 stroke patients received DM199.
The Company may not enroll any additional patients in the ReMEDy2 trial until the Company provides the FDA with the Company’s analysis of the events leading to or causing the hypotension, its suggested protocol modifications to address the mitigation of these events, its rationale and supporting data for the protocol modifications, and the FDA notifies the Company that it may resume enrollment in the clinical trial. Based on information received to date, DiaMedica believes that proportionate reductions in the DM199 dose level and IV infusion times will effectively mitigate the hypotension issue in ReMEDy2 patients. The Company plans to submit a revised ReMEDy2 trial protocol with the supporting rationale and data to the FDA for review upon completion of its compatibility analysis.
Kirsten Gruis, M.D., Chief Medical Officer of DiaMedica, noted that, “Patient safety is very important as we plan and conduct our clinical studies. Patient blood pressure is easily and routinely monitored in stroke patients which is why our study sites were able to quickly identify the issue and immediately stop the dosing of DM199, after which the patients then recovered within minutes and suffered no injuries. We are committed to working diligently with the FDA to resolve this issue and resume the trial as soon as reasonably practicable.”
“While having to pause enrollment in the ReMEDy2 trial was not desirable, we remain confident about the future potential of DM199 and are committed to refining the dosing procedures and methods that will further enhance patient safety,” commented Rick Pauls, DiaMedica’s President and Chief Executive Officer. “We also take comfort in that the transient hypotension observed is yet another clinical indicator that DM199 may be biologically active in stroke patients and may provide a meaningful improvement in stroke outcomes.”
About ReMEDy2 Trial
The ReMEDy2 trial is an adaptive design, randomized, double-blind, placebo-controlled trial studying the use of the Company’s product candidate, DM199, to treat AIS patients. The trial is intended to enroll approximately 350 patients at 75 sites in the United States. Patients enrolled in the trial will be treated for three weeks with either DM199 or placebo, beginning within 24 hours of the onset of AIS symptoms, with the final follow-up at 90 days. The trial excludes patients treated with tissue plasminogen activator (tPA) and/or mechanical thrombectomy. The study population is representative of the approximately 80% of AIS patients who do not have treatment options today, primarily due to the limitations on treatment with tPA or mechanical thrombectomy. DiaMedica believes that the proposed trial has the potential to serve as a pivotal registration study of DM199 in this patient population.
The ReMEDy2 trial has two separate, independent, primary endpoints based upon both the results observed in the first ReMEDy1 phase 2 trial and published results from the urine-derived form of KLK1 used to successfully treat AIS in China. ReMEDy2 is powered for success with either endpoint: 1) physical recovery from stroke as measured by the well-established modified Rankin Scale (mRS) at day 90, and 2) the rate of ischemic stroke recurrence through day 90. Recurrent strokes represent 25% of all ischemic strokes, often occurring in the first few weeks after an initial stroke and are typically more disabling, costly, and fatal than initial strokes.
About DM199
DM199 is a recombinant (synthetic) form of human tissue kallikrein-1 (KLK1). KLK1 is a serine protease (protein) that plays an important role in the regulation of diverse physiological processes including blood flow, blood pressure, inflammation, fibrosis, oxidative stress and neurogenesis via a molecular mechanism that increases production of nitric oxide and prostaglandin. KLK1 deficiency may play a role in multiple vascular and fibrotic diseases such as stroke, chronic kidney disease, retinopathy, vascular dementia, and resistant hypertension where current treatment options are limited or ineffective. DiaMedica is the first company to have developed a recombinant form of the KLK1 protein. KLK1 protein, produced from porcine pancreas and human urine, has been used to treat patients in Japan, China and South Korea for decades. In September 2021, the FDA granted Fast Track Designation to DM199 for the treatment of acute ischemic stroke.
About DiaMedica Therapeutics Inc.
DiaMedica Therapeutics Inc. is a clinical stage biopharmaceutical company committed to improving the lives of people suffering serious diseases. Its lead candidate, DM199, is the first pharmaceutically active recombinant (synthetic) form of the KLK1 protein, an established therapeutic modality for the treatment of acute ischemic stroke and chronic kidney disease. For more information visit the Company’s website at www.diamedica.com.
SOURCE: DiaMedica Therapeutics
Post Views: 116
MINNEAPOLIS, MN, USA I July 06, 2022 I DiaMedica Therapeutics Inc. (Nasdaq: DMAC), a clinical-stage biopharmaceutical company focused on developing novel treatments for neurological disorders and kidney diseases, today announced that the U.S. Food and Drug Administration (FDA) has placed a clinical hold on the Company’s Phase 2/3 ReMEDy2 trial studying the use of the Company’s product candidate, DM199, to treat acute ischemic stroke (AIS) patients. The clinical hold was initiated following the Company’s pause in patient enrollment and submission of three serious adverse event reports to the FDA related to clinically significant, transient hypotension (low blood pressure) occurring shortly after initiation of the intravenous (IV) dose of DM199. The blood pressure levels of the three patients recovered back to their baseline blood pressure within minutes after IV infusion was stopped.
The Company believes that the adverse events resulted from switching to an IV bag formulated from different materials in the ReMEDy2 trial compared to the IV bag used in the prior Phase 2 ReMEDy1 trial. Due to supply issues, the type of IV bag used in the ReMEDy1 trial was not available in many U.S. hospitals, and accordingly after routine compatibility testing, a different type of IV bag was selected for use in the ReMEDy2 trial. As part of the Company’s evaluation of the events that lead to these hypotensive events, the Company is confirming the differences in drug absorption in the IV bags used in the ReMEDy1 trial compared to the ReMEDy2 trial and plans to work with the FDA to modify the ReMEDy2 trial protocol to adjust the DM199 IV dosing to more closely match the dosing in the ReMEDy1 trial, taking into account these differences. The Company notes that no such hypotension issues were reported in its ReMEDy1 trial in which 46 stroke patients received DM199.
The Company may not enroll any additional patients in the ReMEDy2 trial until the Company provides the FDA with the Company’s analysis of the events leading to or causing the hypotension, its suggested protocol modifications to address the mitigation of these events, its rationale and supporting data for the protocol modifications, and the FDA notifies the Company that it may resume enrollment in the clinical trial. Based on information received to date, DiaMedica believes that proportionate reductions in the DM199 dose level and IV infusion times will effectively mitigate the hypotension issue in ReMEDy2 patients. The Company plans to submit a revised ReMEDy2 trial protocol with the supporting rationale and data to the FDA for review upon completion of its compatibility analysis.
Kirsten Gruis, M.D., Chief Medical Officer of DiaMedica, noted that, “Patient safety is very important as we plan and conduct our clinical studies. Patient blood pressure is easily and routinely monitored in stroke patients which is why our study sites were able to quickly identify the issue and immediately stop the dosing of DM199, after which the patients then recovered within minutes and suffered no injuries. We are committed to working diligently with the FDA to resolve this issue and resume the trial as soon as reasonably practicable.”
“While having to pause enrollment in the ReMEDy2 trial was not desirable, we remain confident about the future potential of DM199 and are committed to refining the dosing procedures and methods that will further enhance patient safety,” commented Rick Pauls, DiaMedica’s President and Chief Executive Officer. “We also take comfort in that the transient hypotension observed is yet another clinical indicator that DM199 may be biologically active in stroke patients and may provide a meaningful improvement in stroke outcomes.”
About ReMEDy2 Trial
The ReMEDy2 trial is an adaptive design, randomized, double-blind, placebo-controlled trial studying the use of the Company’s product candidate, DM199, to treat AIS patients. The trial is intended to enroll approximately 350 patients at 75 sites in the United States. Patients enrolled in the trial will be treated for three weeks with either DM199 or placebo, beginning within 24 hours of the onset of AIS symptoms, with the final follow-up at 90 days. The trial excludes patients treated with tissue plasminogen activator (tPA) and/or mechanical thrombectomy. The study population is representative of the approximately 80% of AIS patients who do not have treatment options today, primarily due to the limitations on treatment with tPA or mechanical thrombectomy. DiaMedica believes that the proposed trial has the potential to serve as a pivotal registration study of DM199 in this patient population.
The ReMEDy2 trial has two separate, independent, primary endpoints based upon both the results observed in the first ReMEDy1 phase 2 trial and published results from the urine-derived form of KLK1 used to successfully treat AIS in China. ReMEDy2 is powered for success with either endpoint: 1) physical recovery from stroke as measured by the well-established modified Rankin Scale (mRS) at day 90, and 2) the rate of ischemic stroke recurrence through day 90. Recurrent strokes represent 25% of all ischemic strokes, often occurring in the first few weeks after an initial stroke and are typically more disabling, costly, and fatal than initial strokes.
About DM199
DM199 is a recombinant (synthetic) form of human tissue kallikrein-1 (KLK1). KLK1 is a serine protease (protein) that plays an important role in the regulation of diverse physiological processes including blood flow, blood pressure, inflammation, fibrosis, oxidative stress and neurogenesis via a molecular mechanism that increases production of nitric oxide and prostaglandin. KLK1 deficiency may play a role in multiple vascular and fibrotic diseases such as stroke, chronic kidney disease, retinopathy, vascular dementia, and resistant hypertension where current treatment options are limited or ineffective. DiaMedica is the first company to have developed a recombinant form of the KLK1 protein. KLK1 protein, produced from porcine pancreas and human urine, has been used to treat patients in Japan, China and South Korea for decades. In September 2021, the FDA granted Fast Track Designation to DM199 for the treatment of acute ischemic stroke.
About DiaMedica Therapeutics Inc.
DiaMedica Therapeutics Inc. is a clinical stage biopharmaceutical company committed to improving the lives of people suffering serious diseases. Its lead candidate, DM199, is the first pharmaceutically active recombinant (synthetic) form of the KLK1 protein, an established therapeutic modality for the treatment of acute ischemic stroke and chronic kidney disease. For more information visit the Company’s website at www.diamedica.com.
SOURCE: DiaMedica Therapeutics
Post Views: 116
