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Using Advanced Imaging Biomarkers to understand if your drug works Dr. Olga Kubassova, Founder and CEO of Image Analysis 15/05/2013.

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Presentation on theme: "Using Advanced Imaging Biomarkers to understand if your drug works Dr. Olga Kubassova, Founder and CEO of Image Analysis 15/05/2013."— Presentation transcript:

1 Using Advanced Imaging Biomarkers to understand if your drug works Dr. Olga Kubassova, Founder and CEO of Image Analysis 15/05/2013

2 Clinical Trials Today Competition Baminnercept (BG9924), Biogen, an agent in development for rheumatoid arthritis (RA) and lupus, which targets lymphotoxin-beta, a component on the surface of cells that signals the inflammatory process to begin. Denosumab (AMG 162), Amgen, which targets RANK ligand, a protein involved in the development of bony erosions in Rheumatoid Arthritis and bone loss in osteoporosis. Ofatumumab (HuMax-CD20), GSK an infused biologic designed to reduce the number of B cells, which may decrease disease activity in Rheumatoid Arthritis Belimumab (Benlysta), Human Genome Sciences/GSK, which inhibits the activity of B-lymphocyte stimulator (BLys), a protein that causes B cells to grow in number and perhaps produce antibodies. Belimumab is in development for lupus as well as RA. Canakinumab (Ilaris), Novartis, which targets the proinflammatory cytokine interleukin-1 beta (IL-1β). Approved for a rare autoimmune disorder called cryopyrin-associated periodic syndrome (CAPS), canakinumab is currently in clinical trials for Rheumatoid Arthritis and Juvenile Arthritis. Fostamatinib disodium, AZ, an agent that works by blocking the effects of a protein called syk kinase, which helps B-cells to mature. Fostamatinib disodium is in clinical trials for Rheumatoid Arthritis. Masitinib, AB Science, which inhibits the activity of mast cells, which become activated and contribute to joint inflammation in RA. Masitinib is taken orally and has been in clinical trials for RA. ……Lexicon Genetics, Pfizer,Galapagos, Vertex, Morphosys, Lilly, Rigel/AstraZeneca, Takeda, Abbvie…. Regulatory Late Phase Trials Fail: ‘Trial with HuMax-CD4 in Patients With Rheumatoid Arthritis Failing Treatment With Methotrexate and a TNF-alpha Blocker’, Celltrion terminates European Phase III trial of Rituxan biosimilar, April 2013 Head to Head Trials don’t always succeed : ‘AZ's fostamatinib inferior to Humira in mid-stage RA trial, 2012’ 2-12- 13/AZ_s_fostamatinib_inferior_to_Humira _in_mid-stage_RA_trial.aspx’ 2-12- 13/AZ_s_fostamatinib_inferior_to_Humira _in_mid-stage_RA_trial.aspx ‘AstraZeneca has suffered another clinical setback after its investigational rheumatoid arthritis pill fostamatinib failed to match the efficiency of Abbott's blockbuster Humira.’ Budget Cuts Time Pressure

3 Why Clinical Trials Fail? The compound is ineffective. The dose or the dosage schedule administered is ineffective The compound is administered at the wrong time in the disease process. The trial population group may be inappropriate for demonstrating the effect of the agent. The outcome measures used to determine drug effect may lack the sensitivity to detect a change.

4 X-ray Use of X-ray will only allow seeing late manifestations of the inflammatory disease (such as bone erosions in Rheumatoid arthritis studies) Markers extracted from X-rays will certainly not make your drug efficacy competitive

5 Use of Advanced Imaging - MRI MRI allows seeing early disease manifestations: -synovitis or oedema in Rheumatoid Arthrits, which precede erosions. Erosions themselves will be shown on X- ray up to 2 years after they were seen in MRI -Tumors at earlier stages in MRI of breast patients

6 Quantification of MRI with sensitive metrics However, application of insensitive or qualitative metrics to quantify MRI will not make the full use of the information provided by MRI -If tumours are quantified using simplistic RESIST criteria (in effect measuring tumour diameter) gives a very crude measure of tumour shrinkage but doesn’t assess inflammatory activity -synovitis is measured by visually making a judgement of how much activity there is in the joint or using manual placement of Region of Interest, the measurements done by 2 people will have up to 25% variation

7 Solution: Sensitive Imaging to visualise the effect of treatment Quantitative Imaging Methods to show the effect of treatment Appropriate Infrastructure for multi-centres trials

8 IA team and Independent Clinical Advisory Board have worked in close collaboration with clinical specialists and radiologists specialising in MSK, Oncology, Neurology and Cardiology focusing on quantification of inflammation and perfusion. Dr. Mikael Boesen, MD Parker Inst. Copenhagen, Denmark Dr. Olga Kubassova Olga is a CEO of IA, which she founded in 2007 after completing her PhD on ‘Development of Algorithms for Dynamic MRI Data Analysis’ UK. Olga co- authored of over 40 papers, 5 book chapters and books. Olga and the Clinical Board oversee each clinical trial design to ensure the most effective use of imaging Prof. Peter Taylor, Kennedy School of Rheumatology, Oxford, UK Nikolay Tzaribachev, MD Tuebingen, Germany Dr Omer Aras, Phd Sloan Kettering Cancer Centre, NY, USA

9 Quantitative Imaging + Infrastructure Computer-aided Detection of tumors, lesions, inflamed tissues to speed up and standardize image reading Metrics are quantified and objective Computer support allows for over 95% reproducibility of the results Ability to detect even slightest changes to analyse the impact of treatment early Comprehensive set of imaging markers to build treatment response profile to it differentiate from the competition Quality Control Assessment Image /Biomarker Reading Data Management Validation: over 40 papers Used: world-wide, over 25 installations in clinics and support of major clinical trials Regulatory: Class Iia, CE, ISO13485, CRF21-11 (pending), FDA510K (pending)

10 BaselineDay 1Day 2Day 7 Boesen, M; Kubassova, O et al, Arthritis 2011 Earliest Efficacy Indication, RA: Radiological Assessment of the Rheumatoid Arthritis knee with RAMRIS: Synovitis: Baseline: 1; Day 1: 1; Day 2: 1, Day 7: 1: no response to treatment Radiological Assessment of the Rheumatoid Arthritis knee with DEMRIS, Dynamika: imaging remission on Day 2

11 Automated Detection and Quantification Fully Automated Detection of tumor in DCE-MRI of breast using Dynamika’s pixel-by-pixel iMAPs approach: - In colours, active inflamed tissues, redder colours show less activity, bright, yellow colours - more Brain Tumors iMAPs with Dynamika, Image Analysis

12 Comprehensive assessment of DCE-MRI dataset from RA patient ME – Maximum Enhancement highlights tissues that retain contrast where red indicates low or no inflammatory activity and white/yellow high activity. GD – Contrast Uptake Pattern highlights regions where contrast was absorbed, retained and was quick to diffuse out of tissues over time. TONSET – Contrast Absorption Time highlights the initial time point where contrast was absorbed into tissues TWASHOUT – Time of Washout highlights the start point where contrast diffuses out of tissues IRE- Initial Rate of Enhancement highlights the how quickly contrast was absorbed IRW – Initial Rate of Washout highlights how quickly contrast diffuses out of tissues Automated mapping of inflammatory activity with Dynamika’s parametric maps

13 Automated Detection and Quantification Prostate Cancer Imaging Data Analysis Cardiac Perfusion Brain Tumors Osteoarthritis Nail bed inflammation in PsA

14 Use of Dynamika in a Clinical Trial In a TrialOperationsMarketing Analysis and interpretation of medical images is more reliable, less reader-dependent, and easier to accomplish. Faster data allow better patient monitoring and coordination between sponsor and sites Increased reliability of the quality of the imaging data to support regulatory filings. Lower variability and bias across readers Less training is needed Reduction of missing, lost or incomplete data leading to stronger statistical power and reduction of number of patients to enrol Robust dossier to support approval from Health Authorities Better evaluation of the drug candidate / new therapeutic strategy efficacy. Improved go/no go decisions Technology support allows less patients, faster data lock and immediate cost saving Supportive evidence to Pricing and reimbursement committees Direct access to retrospective data set to perform additional analysis for therapy assessment Full transparency over project activities near real time information, rapid feed –backs to the sites. Seamless translation of results into clinical practice

15 @OlgaKubassova or @ImageAnalysisUK E: Summary Dynamika is a powerful tool used to support superior image analysis We provide full support for imaging trials and improve the accuracy, objectivity and standardization of the image reading allowing for –Detection of even slightest changes, which otherwise might have been missed –Automating routine reading and saving time and costs Platform validated in over 40 publications and by major pharma, KOLs and physicians CE mark granted by BSI in 2011, FDA510K pending

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