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TORONTO, Feb. 01, 2023 (GLOBE NEWSWIRE) -- PharmaTher Holdings Ltd. (the "Company" or "PharmaTher")
PHRRF, a leader in advancing specialty ketamine pharmaceuticals, today submitted its meeting package with the U.S. Food and Drug Administration ("FDA") to discuss advancing KETARX™ (racemic ketamine) into Phase 3 development as a treatment for levodopa-induced dyskinesia in Parkinson's disease ("LID-PD"). This Type C meeting allows the Company to discuss with the FDA its plans for a Phase 3 clinical study to support the submission of a new drug application under the 505(b)(2) regulatory pathway for KETARX™ in treating LID-PD. In addition, the Company has requested guidance from the FDA to obtain Fast Track Designation for KETARX™. The Type C meeting is via written responses. The goal date for the FDA in providing its written responses is March 20, 2023.
The Company believes the safety and efficacy results from its previously announced presentation of the completed clinical study may support the investigation of KETARX™ in a proposed Phase 3 clinical study as a potential new treatment for LID-PD.
Summary results of the study:
* Enrolled subjects with moderate to advanced Parkinson's disease with a target infusion rate being 0.30 mg/kg/hr. Data highlight that ketamine was safe, well-tolerated, and demonstrated that 100% of subjects treated with ketamine had a reduction in dyskinesias as measured by UDysRS.
* UDysRS showed a 51% reduction from baseline during Infusion 2 (p=0.003), 49% at 3 weeks (p=0.006) and 41% at 3 months (p=0.011) post-ketamine.
* The maximum tolerated infusion rate ranged from 0.20-0.30 mg/kg/hr, which was dependent on either discomfort due to dissociation or hypertension. There were no adverse events post-infusion.
Patent
PharmaTher retains rights to US Patent No: 11,426,366 (expires May 2036), titled "Compositions and Methods for Treating Motor Disorders," which includes claims intended to cover ketamine in the potential treatment of Parkinson's Disease and motor disorders that cause involuntary or uncontrollable movement or actions of the body.
Fast Track
Fast Track is a process designed to facilitate the development and expedite the review of investigational drugs to treat serious conditions and fill an unmet medical need. Drugs that receive Fast Track Designation may be eligible for more frequent communications and meetings with the FDA to discuss the drug's development plan, including the design of the proposed clinical trials, and ensure the collection of appropriate data needed to support approval. Clinical programs conducted under Fast Track Designation may be eligible for Accelerated Approval and Priority Review of new drug applications if relevant criteria are met.
Trial
Randomized, Double-Blind, Active Placebo-Controlled Study of Ketamine to Treat Levodopa-Induced Dyskinesia
clinicaltrials.gov/ct2/show...
Ketamine’s Potential In Parkinson’s Disease
Ketamine is an FDA-approved N-methyl-D-aspartate receptor-modulating (NDMA) drug that is widely used as an anesthetic agent either alone or in combination with other anesthetic agents [Smith et al, 1987; Pacheco et al, 2014]. The possible therapeutic effect of low-dose ketamine on levodopa-induced dyskinesia was noted in a retrospective analysis of Parkinson’s disease patients who received ketamine for pain relief. During this analysis, it was observed that the patients experienced an improvement in LID lasting several weeks beyond treatment [Sherman et al, 2016]. These results were corroborated in a test of low-dose ketamine in a rodent LID model, and this possible effect has also been examined in a controlled study [Bartlett et al, 2016]. Ketamine may also have additional benefits in the treatment of pain [Niesters et al, 2014] and depression [Diamond et al, 2014; Murrough et al, 2013], which are frequent comorbidities of Parkinson’s disease.
About Ketamine
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it is good for depression as well
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PharmaTher currently holds five orphan drug designations granted by the FDA for KETARX™ (racemic ketamine), which include:
* Treatment of Rett Syndrome;
* Prevention of Ischemia-reperfusion injury from organ transplantation;
* Treatment of Status Epilepticus;
* Treatment of Amyotrophic Lateral Sclerosis; and
* Treatment of Complex Regional Pain Syndrome.
Ketamine’s Potential In Rett syndrome
Ketamine has the potential to treat Rett syndrome, which has been independently validated in two different laboratories in two different strains of Mecp2 mice and has completed a Phase 2 clinical trial with Rett syndrome, with results not published. The therapeutic potential of ketamine for treating Rett syndrome was first demonstrated by Dr. David M. Katz, Professor Emeritus, Department of Neurosciences, School of Medicine at CWRU, and colleagues, who found that treatment of heterozygous female Mecp2 mutant mice with a subanesthetic dose of ketamine (8 mg/kg) acutely reversed abnormalities in Fos expression and sensorimotor function [1]. Chronic administration of ketamine was also found to improve symptoms and extend lifespan in null male Mecp2 mutants [2].
The ability of low-dose ketamine to improve function across a broad range of symptoms may be related to its ability to increase cortical network activity, possibly by selective inhibition of GABAergic interneurons [3], as well as to decrease synaptic excitability in brainstem networks important for respiratory and autonomic control [4]. Thus, ketamine may be ideally suited to redress the imbalance between cortical and brainstem activity that characterizes the MeCP2-deficient brain. Moreover, in addition to its acute effects on circuit function, work in other disease models has shown that ketamine also rapidly stimulates dendritic growth, BDNF levels, and expression of key synaptic proteins [5, 6], at least in part through activation of mTOR signalling, which is deficient in Mecp2 mutants [7]. These findings suggest that, in addition to acute rescue of neurological function, ketamine also has the potential to promote synaptic repair in Rett syndrome by enhancing structural and functional connectivity, as previously shown in animal models of depression and stress [8].
The Orphan Drug Act
The Orphan Drug Act grants special status to a drug or biological product to treat a rare disease or condition upon request of a sponsor. This status is referred to as orphan designation (or sometimes “orphan status”). The FDA grants orphan status to products that treat rare diseases, providing incentives to sponsors developing drugs or biologics. The FDA defines rare diseases as those affecting fewer than 200,000 people in the United States at any given time. Orphan drug designation would qualify ketamine for certain benefits and incentives, including seven years of marketing exclusivity if regulatory approval is ultimately received for the designated indication, potential tax credits for certain clinical drug testing costs, eligibility for orphan drug grants, and the waiver of the FDA New Drug Application filing fee of approximately $2.4 million.
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