Phytopharm plc (PYM: London Stock Exchange) (“Phytopharm”, the “Group” or the “Company”) have announced the results of the Phase II, randomised, double blind, placebo controlled, dose-ranging trial of Cogane™ in unmedicated patients with early-stage Parkinson’s disease (“CONFIDENT-PD”).
Analysis of the headline results indicated that Cogane™ had no beneficial effects on patients’ symptoms measured by the primary or secondary endpoints in the study.
Over four hundred subjects with early-stage Parkinson’s disease were randomly allocated to receive either Cogane™ 60 mg, 120 mg or 180 mg, or placebo, which was taken orally, once daily for up to 28 weeks. Measurements were taken during the study to determine the efficacy, safety and tolerability of each dose of Cogane™ compared with placebo and also the systemic exposure to Cogane™.
The prospectively defined primary endpoint in this study was the change in the combined UPDRS II/III (an assessment of activities of daily living and motor symptoms) score from baseline to end-of-treatment for each dose of Cogane™ vs. placebo. A number of secondary efficacy outcome measures were also explored.
No statistically significant effects or trends towards improvement were seen in any of these endpoints. Analysis of the results indicates that the study was well conducted and gave a clear, albeit negative result.
Review of the safety data confirmed that Cogane™ administered orally once daily for up to 28 weeks was well tolerated.
The full results of the study will be published in an appropriate scientific forum in due course.
Professor C Warren Olanow, Professor of Neurology and Neuroscience at Mount Sinai Medical School and Co-chief Investigator for the study commented: “This is disappointing news for the Parkinson disease community. Trophic factors that enhance and restore function to remaining nerve cells is an extremely promising approach for the treatment of neurodegenerative disorders such as Parkinson’s disease. Cogane™ offered the potential of providing trophic effects throughout the brain with an oral medication that was relatively safe and well tolerated. The company is to be congratulated for carrying out this important study in such a high quality manner. Sadly, the results are negative. Nonetheless, the search for more effective therapies for the millions of patients who suffer from Parkinson’s disease must continue.”
Commenting on these results, Tim Sharpington, CEO said: “We are naturally disappointed with the outcome of this study of Cogane™ in patients with Parkinson’s disease. Cogane™ had demonstrated encouraging efficacy in a wide range of industry standard pre-clinical models but this promise has not translated into clinically meaningful efficacy in this study. I would like to thank the investigators who conducted the trial, our collaborators and especially the patients who participated in the study, along with the Parkinson’s disease community and all our stakeholders who have supported the development of Cogane™.
During the coming weeks we will further analyse these results with our scientific advisors to better understand whether to continue the development of Cogane™ and Myogane™. In addition, a review of other strategic options for the Company will be initiated by the Board and shareholders will be kept informed of progress. No further R&D expenditure will be committed whilst this review is taking place.”
Parkinson’s disease (“PD”) is a movement disorder affecting 1 in 100 people over 60 years of age and is characterised by muscle rigidity, tremor and a slowing of physical movement (bradykinesia) and, in extreme cases, a loss of physical movement (akinesia). The primary symptoms are the result of altered signalling in an area of the brain, the striatum, responsible for the control of movement. This is caused by degeneration of dopaminergic neurones that project from the substantia nigra to the striatum, leading to insufficient formation and action of dopamine. Parkinson’s disease is therefore termed a neurodegenerative disease. The disease is relatively slow in its onset, with the appearance and worsening of symptoms reflecting the progressive loss of dopaminergic neurones. There is increasing awareness within the field, of the non-motor symptoms of PD (e.g. cognitive impairment, depression and anxiety, sleep difficulties, anosmia, constipation, speech problems), which have a major impact on patients and their families/carers.
Most patients with PD have only a slightly reduced lifespan, although quality of life during the advanced staged of the disease is often poor especially for those patients with dementia. Patients often become severely disabled as symptoms cannot be adequately controlled by current drug therapies, which may also be associated with severe side effects.
Cogane™ in Parkinson’s disease
Cogane™ has previously been shown to demonstrate neuroprotective and neurorestorative properties in a number of industry-standard preclinical models of Parkinson’s disease and other neurodegenerative diseases conducted at independent laboratories. It has been formulated as a once-daily oral medication which was shown to be well tolerated and have good bio-availability in Phase I clinical studies.
The CONFIDENT-PD trial was a multi-national, Phase II, double blind, placebo controlled, dose ranging clinical trial which compared the efficacy, safety and tolerability of three doses of Cogane™ with placebo, when administered for 28 weeks to unmedicated patients with early-stage Parkinson’s disease. Importantly, this trial assessed the ability of Cogane™ to affect both the motor and non-motor symptoms of Parkinson’s disease. In this trial, over 400 patients were randomised across more than 90 sites in North America and Europe.
The primary efficacy endpoint of the CONFIDENT-PD clinical trial was the change from baseline to end-of-treatment on the Unified Parkinson’s disease rating scale (“UPDRS”), Parts II and III combined. The UPDRS is a well-established and widely-used tool used to assess patients’ PD symptoms. UPDRS Part II is an assessment of the impact of PD on activities of daily living (“ADL”), which include routine tasks such as doing up buttons and shoe laces. UPDRS Part III is an assessment of patients’ motor symptoms (e.g., gait, bradykinesia, postural stability, tremor).
The scales for outcomes in Parkinson’s disease-cognition tool (“SCOPA-COG”) is an assessment designed specifically to assess the impact of PD on cognitive function by measuring performance on a number of tasks relying on memory, learning ability, level of attention, executive decision-making and visuo-spatial function. The non-motor symptom scale (“NMSS”) is a rating scale used to assess a broad spectrum of important non-motor features associated with PD.
The Parkinson’s disease 39 instrument (“PDQ-39″) is a quality-of-life (“QoL”) questionnaire which generates a profile of scores, providing a subjective indication of the effect of PD on patients’ QoL
The Beck depression inventory, 2nd revision (“BDI-II”) is a questionnaire for assessing depression.
The Epworth Sleep Scale (“ESS”) is a well-established questionnaire used to assess the level of excessive daytime sleepiness.
Source: Phytopharm plc