Implant Evaluated for Alzheimer's Disease

The study will measure the safety and efficacy of DEBIO-9902 SR implants, in comparison to oral donepezil, in a clinical trial named ‘BRAINz' (Better Recollection for Alzheimer's patients with Implants of ZT-1).

Debiopharm (Lausanne, Switzerland), a biopharmaceutical development company specializing in oncology and serious medical conditions, announced its first patient has enrolled in the phase II study with DEBIO-9902 SR implants (formerly ZT-1), the first monthly sustained-release AChE inhibitor being developed for Alzheimer (AD) patients.

"This is a promising new therapeutic approach,” said Dr. David Wilkinson, from the Moorgreen Hospital (Southampton, UK) and principal investigator in the United Kingdom. "The DEBIO-9902 SR implant provides a new treatment alternative with the potential for better tolerance through a progressive, steady release of the active compound. This becomes an important factor in terms of compliance and efficacy for Alzheimer's patient who may find taking regular oral medication difficult or distressing.”

The phase II, double-blind, double-dummy clinical trial with DEBIO-9902 SR, which will be conducted on three continents, received prompt positive opinions from the ethics committee and regulatory agencies and was approved in the record time of one month. Results are expected during the first half of 2008.

Results of an open label, phase II study with a once daily oral formulation of DEBIO-9902 demonstrated efficacy in mild to moderate AD patients, according to the Alzheimer's assessment cognitive sub-scale (ADAS-cog), the Mini mental state examination (MMSE), as well as by the Neuropsychiatric inventory questionnaire (NPI-Q). DEBIO-9902 was found to be safe for doses up to 2 mg per day. A prior phase I implant study showed that DEBIO-9902 SR implants were safe up to a dose of 15 mg/month and continuously released the active pharmaceutical ingredient over a period of 28 days.

Current estimates show that approximately four million people suffer from AD in the United States and 15 million worldwide. Most available treatments produce an increase of the acetylcholine levels by inhibiting AChE, the enzyme responsible for its breakdown. Currently used therapies have significant side-effects that can occur with a frequency of up to 50% for nausea, for instance. These treatments generally require complicated titration schemes to minimize these cholinergic side-effects, which is a challenge when dealing with memory-deficient patients.

An AChE inhibitor with a better tolerance profile than existing treatments and with an easier dosing schedule could improve patient compliance and therefore optimize the patient's treatment. DEBIO-9902 SR is an innovative AChE inhibitor that is transformed non-enzymatically into its active compound, huperzine A (hup A).

Hup A has been used in China for centuries to treat distinct disorders such as memory loss, schizophrenia, and hypertension, and is widely used in North America and Europe as a food additive to enhance cognition and neuroprotection. The dual mode of action of DEBIO-9902 SR as an N-methyl-D-aspartate receptor antagonist and an AChE inhibitor, positions it as a third generation anti-Alzheimer's product by improving the general condition and cognitive functions of affected patients as well as having the potential of being a neuroprotectant. A compound with neuroprotective properties to complement the cholinergic effects could potentially reduce the progression of AD.


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