Pharma-Cog

Prediction of cognitive properties of new drug candidates for neurodegenerative diseases in early clinical development
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FACTS & FIGURES

Start Date
End Date
Call
IMI1 - Call 1
Grant agreement number
115009

Contributions
IMI Funding
9 685 388
EFPIA in kind
11 690 333
Other
7 422 044
Total Cost28 797 765

Summary

​​​​​​​When it comes to Alzheimer’s disease (AD), most potential drug candidates fail during clinical trials, resulting in significant setbacks in the development of effective treatments. IMI’s Pharma-Cog project set out to change that. The project developed a matrix of biomarkers which can be used to study the effect of a drug candidate both in animals and humans, and has the potential to more accurately predict the success of future drugs in early stages of drug development. Pharma-Cog scientists also found a better way to stratify patients with early signs of Alzheimer’s disease, which may lead to more definitive clinical trials. All this has the potential to help pharmaceutical companies conduct more efficient and more precise clinical trials in the future, speeding up the development of AD drugs. At least one biotech company is already using the results of Pharma-Cog to test a promising new drug candidate.

A challenging disease

Over 4 million Europeans suffer from Alzheimer’s disease (AD), and the cost of the disease in the EU amounted to more than 100 billion in 2008. Currently approved drugs for patients with Alzheimer's disease only treat symptoms (symptomatic approach) and their effect is limited or absent in many patients. No drugs have been approved yet that can actually slow the progression of the disease (disease modifying approach). Trials with candidate drugs take years and cost tens of millions of euros. Furthermore, a number of AD drugs which showed promise in the laboratory didn’t translate into success in the clinic, resulting in a high number of costly drug failures.

The Pharma-Cog project aimed to develop and validate new tools to test candidate drugs for the treatment of symptoms and disease in a faster and more sensitive way. By bringing together results from blood tests, electroencephalography (EEG) recording of brain activity, magnetic resonance imaging (MRI) scans, and behavioural tests, the scientists set out to develop a more comprehensive matrix of clues (biomarkers) that may give more accurate information on the progression of the disease and the effect of candidate drugs than current approaches. The project worked in three core areas: preclinical work with animal models; experimental medicine work involving healthy volunteers that undergo a challenge, such as sleep deprivation; and patients with mild cognitive impairment (MCI), an early sign of Alzheimer’s.

Improving translatability between animals, healthy volunteers and patients

In order to find biomarkers which could help predict the effectiveness of a new drug candidate in the early stages of drug development, Pharma-Cog scientists measured the effect of known Alzheimer’s drugs in all three core areas above. By cross-checking the results, they identified and validated a matrix of biomarkers, such as EEG recordings of brain activity and MRI scans, which could help predict the effect of drugs more accurately. For example, they demonstrated that some changes in the rhythm of brain activity observed via EEG are a good marker to detect the effect of a new drug in early studies involving both human and animal models. This important discovery could help pharmaceutical companies make better decisions on which drugs are worth pursuing in clinical trials, and do this much earlier, before starting the more costly studies in patients. A French biotechnology small and medium-sized enterprise (SME) is already using some of these findings to evaluate a promising new AD drug candidate.

Improving stratification of patients

An important part of the project was a study involving more than 150 patients with MCI. MCI is one of the early signs of Alzheimer’s but not all patients who have it will go on to develop the disease. In clinical studies involving MCI patients, the effect of a potential drug candidate can be masked by this variability among patients.

By monitoring a group of MCI patients over a longer period of time, and taking measurements such as EEG readings, MRI scans and blood tests, Pharma-Cog scientists were able to identify a set of biomarkers which signal whether a patient is likely to progress to Alzheimer’s or not. This important discovery has the potential to improve the stratification of AD patients in future clinical trials, making it more sensitive and effective.

Other achievements

In addition to improving translatability between animal and human studies, and improving the stratification of patients, the project recorded a number of other achievements, including:

  • Reconciling the symptomatic and disease modifying approaches to AD therapy, and highlighting the need for improved symptomatic drugs despite the emphasis on disease modification.
  • Building a large database which contains data on the effect of AD drugs on a matrix of biomarkers. As some studies are still ongoing, this database is currently open to only Pharma-Cog partners, but it will eventually be opened up to other researchers.
  • Demonstration that healthy humans and animals who have been sleep-deprived for one night show some of the same changes in brain activity as AD patients, and can be used in early studies to predict the effectiveness of new drug candidates.
  • Thanks to Pharma-Cog, a French SME was able to validate a diagnostic kit for AD, which they had developed before the project. The kit contains inflammatory proteins which show correlation with the worsening of the disease. A patent application is pending.
  • As the European Medicines Agency was a full partner in the project, the findings could have an impact on the revision of EMA guidelines on medicines for Alzheimer’s. Discussions with the agency are still ongoing.
  • Strengthening collaboration between key players in the Alzheimer’s disease field, including industry, academia and SMEs. The collaboration is continuing and could result in future projects.

For the benefit of industry, academia, and patients

The academic partners benefited from the project by gaining international visibility, strengthening their collaboration with industry and learning more about the drug development process, including the high standards of robustness and rigour of data that industry requires before further investment into novel drugs or technologies. Many publications and communications have also resulted from the project.

The industry also benefited from the collaboration with academia, SMEs and other industry partners. In the long term, the outputs of Pharma-Cog could help pharmaceutical companies make better decisions on which drugs are worth pursuing in clinical trials, saving them money and resources. Additionally, the stratification of patients devised in Pharma-Cog could make clinical trials more sensitive.

But it will be the patients who will benefit the most. Thanks to Pharma-Cog, future clinical trials may require smaller sample sizes and shorter duration, which could speed up the development of new AD drugs for the benefit of patients.

Thanks to the participation of a patient organisation, Alzheimer Europe, as a full partner in the project, Pharma-Cog also enabled patients to gain a better understanding of the drug development process and the challenges of predicting the safety and efficacy of new molecules.

What’s next?

Even though the project has officially ended, several studies are still ongoing and further publications are anticipated. Furthermore, some of the partners within the project are continuing to collaborate and apply for new projects.

Read the interview with project coordinators

Achievements & News

Pharma-Cog results may speed up Alzheimer’s drug development
September 2017

When it comes to Alzheimer’s disease (AD), most potential drug candidates fail during clinical trials, resulting in significant setbacks in the development of effective treatments. IMI’s Pharma-Cog project set out to change that. The project developed a matrix of biomarkers which can be used to study the effect of a drug candidate both in animals and humans, and has the potential to more accurately predict the success of future drugs in early stages of drug development. Pharma-Cog scientists also found a better way to stratify patients with early signs of Alzheimer’s disease, which may lead to more definitive clinical trials. All this has the potential to help pharmaceutical companies conduct more efficient and more precise clinical trials in the future, speeding up the development of AD drugs. At least one biotech company is already using the results of Pharma-Cog to test a promising new drug candidate. ‘We have attracted an SME which didn’t take part in our project’, explained scientific coordinator Régis Bordet, in an interview with the IMI Programme Office. ‘They saw the results of Pharma-Cog and they asked me to help them develop their compound which could be very interesting for AD treatment. The project is worth 3 million euros and has received support from the French government. By early 2019 we will know whether there is a sizeable effect of this compound on Alzheimer’s, and whether it is worth pursuing further in a clinical trial. Thanks to this cooperation, we will have a real-life demonstration that we have done in Pharma-Cog is useful for the development of new compounds for AD patients.’

PharmaCog completes patient recruitment for clinical trial of biomarker matrix
IMI’s Alzheimer’s disease project PharmaCog has completed the recruitment of 150 patients with mild cognitive impairment for a clinical trial of a matrix of biomarkers. ###The human and financial costs of Alzheimer’s disease are growing rapidly as the population ages, but the results of recent clinical trials for Alzheimer’s drugs have been disappointing. The main reason for the failure of these trials is a lack of demonstration of significant efficacy.
The working hypothesis of PharmaCog is that no single physiological, functional or biochemical marker will be sensitive enough to respond to a drug sufficiently to provide the confidence to progress to later clinical phase studies, but that a collection of markers will be necessary. With this in mind, the project is working to develop a biomarker matrix to track disease progression in patients with Alzheimer’s disease and patients with mild cognitive impairment as a novel tool to detect the efficacy of treatments.
PharmaCog’s matrix is a unique tool for the study of Alzheimer’s disease and potential treatments, as it can be applied to laboratory models, human volunteers and patients. By achieving this latest recruitment goal, PharmaCog is on track to test and reach conclusions on the value of the matrix as a tool for tracking disease progression in people with mild cognitive impairment.
(July 2013)

PharmaCog reaches out to European Parliament
IMI project PharmaCog presented some of its key findings at the European Parliament during a lunch hosted by French parliamentarians Françoise Grossetete and Elisabeth Morin-Chartier.###The 40 guests, including 7 Members of the European Parliament (MEPs) learnt about how the PharmaCog project is helping to speed up the discovery of drugs for Alzheimer’s disease. PharmaCog is developing new tools to identify potential drugs (and screen out ineffective ones) early in the drug development process. The project is also working on tests to determine how well a drug is working in individual patients, e.g. through brain scans, blood tests, and cognitive testing.
(March 2012)


Participants Show participants on map

EFPIA companies
  • AstraZeneca AB, Södertälje, Sweden
  • Boehringer Ingelheim International GmbH, Ingelheim, Germany
  • Eisai Limited
  • Eli Lilly and Company Ltd, Basingstoke, United Kingdom
  • F. Hoffmann-La Roche Ltd, Basel, Switzerland
  • Glaxosmithkline Research And Development LTD, Brentford, Middlesex, United Kingdom
  • H. Lundbeck A/S, Valby, Denmark
  • Institut De Recherches Servier S.A.S, Suresnes, France
  • Janssen Pharmaceutica NV, Beerse, Belgium
  • Merck KGaA, Darmstadt, Germany
  • Novartis Pharma AG, Basel, Switzerland
  • UCB Biopharma SPRL, Brussels, Belgium
Universities, research organisations, public bodies, non-profit groups
  • ARC-Net Applied Research On Cancer Centre, University of Verona, Verona, Italy
  • Centre National De La Recherche Scientifique, Paris, France
  • Consorci Institut d'Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain
  • Institut National De La Sante Et De La Recherche Medicale, Paris, France
  • Irccs Fondazione Sdn Per La Ricerca E L'Alta Formazione In Diagnostica Nucleare, Napoli, Italy
  • Istituto di Ricerche Farmacologiche Mario Negri, Milano, Italy
  • Provincia Lombardo-Veneta - Ordine Ospedaliero di San Giovanni di Dio— Fatebenefratelli, Brescia, Italy
  • Stichting VU, Amsterdam, Netherlands
  • The University of Exeter, Exeter, United Kingdom
  • Universidad de Murcia, Murcia, Spain
  • Universitaetsklinikum Essen , Essen, Germany
  • Università Cattolica del Sacro Cuore, Milan, Italy
  • Università degli Studi di Foggia (University of Foggia), Foggia , Italy
  • Università degli Studi di Perugia , Perugia, Italy
  • Università degli studi di Genova, Genova, Italy
  • Universität Leipzig, Leipzig, Germany
  • Université Lille 2 Droit et Santé, Lille, France
  • Université d'Aix-Marseille, Marseille, France
Small and medium-sized enterprises (SMEs)
  • Diaxonhit SA, Paris, France
  • Innovative Concepts in Drug Development (ICDD-sas), Meyreuil, France
  • Qualissima , Marseille, France
  • SAS Alzprotect, Loos, France
Patient organisations
  • Alzheimer Europe, Luxembourg, Luxembourg
  • Greek Association of Alzheimer's Disease and Related Disoders, Thessaloniki, Greece
Third parties
  • Centre Hospitalier Regional De Mars Eille Assistance Publique-Hopitaux Marseille, Marseille, France
  • Centre Hospitalier Regional et Universitaire de Lille, Lille, France
  • Museum National D'Histoire Naturelle, Paris, France
  • Université Paul Sabatier Toulouse III , Toulouse, France

CONTACT

Project coordinator
Graham Somers
GLAXOSMITHKLINE RESEARCH AND DEVELOPMENT LTD
graham.i.somers[at]gsk.com
Managing entity
Isabelle Amabile
Université d'Aix-Marseille
isabelle.amabile[at]univ-amu.fr