Blue sky innovation...continued

Thanks to its significantly improved safety profile, ProveBlue methylene blue opens the way to widespread clinical testing of its pharmacological properties in a number of life-threatening diseases.

Methylene blue is widely used in diagnostic procedures and medical indications, such as methemoglobinemia antidote. More recently, the compound regained momentum in malaria and attracted the attention of clinicians as a promising application in a variety of affections such as dysplasia or pre-cancerous lesions identification, ifosfamide induced encephalopathy and Alzheimer’s.

Despite repeated attempts by many companies, which eventually proved unsuccessful, the available materials until now showed poor quality. The heavy metals content that was repeatedly reported led the European Directorate for the Quality of Medicines to loosen limits on such impurities in the European Pharmacopoeia (EP) monograph.

ProveBlue: free from heavy metals
Through an innovative patented chemistry designed by its mother company, Provence Technologies, Provepharm provides researchers and pharmaceutical companies with the world’s first EP and US Pharmacopoeia (USP)-compliant grade of methylene blue: ProveBlue. The active substance is virtually free from heavy metals and displays an unsurpassed level of purity.

Over the last year, Provepharm’s ambition was geared to reviewing manufacturing and controls of the compound to assure its complete characterisation, anticipate the regulatory requirements applicable to a drug substance and set-up robust and validated manufacturing operations. The company has successfully moved to large-scale industrial production and ProveBlue is now available from a GMP manufacturing site that is regularly inspected by the US Food and Drug Administration and the French medicinal product Agency.

‘In the longer term, Provepharm will be soliciting the EP, the USP, the Brazilian Pharmacopoeia and other bodies to tighten up their specifications and we will be updating the pharmacopoeia with respect to specifications and analytical methods,’ says Jeff Kaufman, R&D director of Provepharm.

Second building block
Capitalising on the substance distinctive purity and while gaining enhanced knowledge of its significantly reduced toxicological profile, Provepharm decided to apply for the marketing authorisation (MA) of the injectable drug (injectable methylthioninium chloride Proveblue EP), first of all in Europe. At the end of June 2009, an important milestone was passed when the EMEA confirmed the eligibility of this product to the European centralised procedure. Based on purely scientific criteria, the CHMP positively assessed the product technical innovation, leading to an improved risk-benefit balance to the patients.

‘We take this as recognition and as a strong encouragement to proceed with a complete update on the product through our Quality by Design approach and the submission of the MA dossier at the end of 2009,’ adds Jeff Kaufman.

Future steps
Provepharm is actively involved in an initiative aiming at investigating ProveBlue in malaria. The compound has no resistance problem and some preliminary testing shows that promising results are obtained. Therefore, it is a candidate drug for inclusion in a future combination therapy as recommended by the World Health Organization.

‘Our strategic initiative is to position ProveBlue as a potentially valuable drug against a number of diseases, among which is life-threatening malaria,’ says Michel Féraud, Provepharm’s CEO. ‘I am also convinced that researchers in other domains will consider ProveBlue’s distinctive safety as early as possible in their clinical trials or development programme.’

Company profile

Provepharm SAS is based in Marseilles, France.

For more information, visit:
www.provepharm.com.