BIOPROJET PHARMA, RESEARCH & DEVELOPEMENT
Most of the products developed by Bioprojet are “First in Class”, in other words, they are the leaders in a new class of drugs. These include Racecadotril, an enkephalinase inhibitor, and Pitolisant, antagonist/inverse agonist of histamine H3 presynaptic receptors, or BP1.4979, a partial agonist of the dopamine D3 receptor.

These products are new chemical entities, and most of them have original mechanisms of action. Obtaining a marketing authorisation (MA) entails completing a comprehensive pharmaceutical, preclinical and clinical development process.

The Clinical Development Department in Paris takes charge of the drug candidates from the Bioprojet Biotech research centre to conduct the pharmaceutical development and therapeutic trials in humans from phase I to phase III and to obtain product regulatory registration in the selected indications.

PHARMACEUTICAL DEVELOPMENT
The development and preparation of pharmaceutical forms (tablets, sachets, i.v. solutions…) are performed according to Good Laboratory Practice by specialized subcontractors, on the initiative and under the supervision of Bioprojet pharmacists who provide regulatory approval for use.

PHASE I
Phase I studies are the first time a substance is administered to healthy volunteer humans (“First In Human”). The products are first administered in gradually increasing single doses, then in repeated doses, to assess PK parameters and tolerability. This method is used to determine the maximum tolerated dose and to define the dosage level to be tested for efficacy under phases II and III.

Other phase I studies are carried out on specific populations (young or elderly subjects, paediatric populations, kidney or liver failures, the effect of food intake, subjects from different racial groups etc.), and on the metabolism, in particular with a radio-labelled product, or on cardiovascular safety.

These clinical trials are conducted in specialized centres, following protocols provided by Bioprojet physicians who are monitoring their execution, while bioassays are carried out by Bioprojet Biotech.

PHASE II
These “proof of concept” studies assess the product efficacy and safety, and lay down active doses in a limited number of patients for the target indications set out on the basis of their mechanism of action. They are particularly important to identify the therapeutic indications of the new classes of agents created by Bioprojet.

PHASE III
These double blind, randomized studies against placebo or a reference product confirm the efficacy and safety of medicines. Conducted on wider cohorts of patients with a disease previously identified during phase II, they also allow for product comparison among existing therapies.

Phase II or III studies are usually multicenter trials conducted in the hospitals of several European countries. Bioprojet clinicians and clinical research associates write out the protocol, and ensure follow-up according to Good Clinical Practice and international harmonization requirements (ICH), with the participation of assistants working for companies under contract in the countries of enforcement. European scientific committees participate in the elaboration of protocols and check their implementation throughout the development, periodically assessing the risk benefit ratio for patients.

The study results are evaluated by methodologists and statisticians outside Bioprojet, which drafts the report to be submitted to the Medicines Agencies.

BIOPROJET THERAPEUTIC AREAS
Pitolisant, the first histamine H3 receptor (H3R) antagonist, was developed for its awakening effect in the treatment of narcolepsy with or without cataplexy. A European MA was obtained for this indication in March 2016 (Wakix®). A paediatric investigation plan is underway and studies are being carried out in narcoleptic children.

Pitolisant has also been developed for treating excessive daytime sleepiness (EDS) related to sleep apnoea and Parkinson’s disease. It is the subject of several international multicentre phase III studies.

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