Alzheimer s Disease Research

Transcription

1 PRA INSIGHTS REPORT Alzheimer s Disease Research JULY 2017 Page 01 of 9

2 TABLE OF CONTENTS Introduction Methodology Summary Question One: Demographics Question Two: The Foremost Challenge in Neuroscience Drug Development Question Three: Promising Threads in Alzheimer s Research Question Four: Recruitment of Prodromal Subjects Question Five: Barriers Toward Participation in Alzheimer s Disease Trials Question Six: The Future of Alzheimer s Disease Research External Sources Page 1 of 9

3 INTRODUCTION The Alzheimer s Association International Conference (AAIC) is the world s largest forum for dementia research, attended by approximately 5,600 individuals from industry, academia, non-profit organizations and government bodies. Following the success of the PRA Insights survey which took place at DIA US, PRA s Neuroscience and Pain team piloted the scheme in Europe with a short, primarily multi-choice questionnaire, run across all four exhibition days to gather insight on clinical development and the future of research in Alzheimer s disease. The questions were as follows: 1. What do you believe is the foremost challenge in neuroscience drug development? Target identification/validation Regulatory review and approval Uncertainty/risk Funding 2. What do you believe is the most promising thread of Alzheimer s research? Amyloid hypothesis Tau protein Beta-secretase (BACE) Hormonal research Inflammation 5HT6 receptor 3. What do you believe could impact recruitment of prodromal Alzheimer s patients in a positive way? Interacting with online patient communities Digital screening of potential subjects with self-reported cognitive symptoms Pre-screening in the community Streamlining site visits combined with virtual reporting tools 60/40 alternate allocation ratio towards active treatment 4. What do you feel are the main barriers toward participation in Alzheimer s trials? (pick the 3 most important) Low trial awareness Comorbidities Concomitant medications Risks of side effects Barriers associated with procedures (eg. unwillingness to undergo procedures such as lumbar puncture) Risk of placebo Travel and other logistics Informed consent Page 2 of 9

4 5. Do you believe that a Disease Modifying Drug for Alzheimer s will have been discovered by target 2025? Yes No METHODOLOGY Data for this report was gathered during exhibit hours at the Alzheimer s Association International Conference (AAIC) over July, PRA ran a single survey over the four exhibition days, obtaining a total of 119 responses. Participants self-selected their company affiliation from four choices: CRO Investigator/Site Pharmaceutical/Biotechnology company Service/product provider Of the 119 responses, the majority (57%) identified as coming from an Investigator/site background, followed by 24% from pharma/biotech, 10% for Service/product provider to the industry and 9% from a CRO. This largely reflected the attendance of the conference itself. SUMMARY QUESTION ONE: WHICH CATEGORY BEST DESCRIBES YOU? (N=119) Question 1 CRO 11% Service/Product Provider 12% AAIC 2017 (N = 119) Pharma/Biotech Company 29% Investigator/Site 67% Page 3 of 9

5 QUESTION TWO: WHAT DO YOU BELIEVE IS THE FOREMOST CHALLENGE IN NEUROSCIENCE DRUG DEVELOPMENT? (N=118, 1 PERSON SKIPPED) This question was selected to address the fact that despite major advances in science and our understanding of the brain, research has not yet translated into meaningful therapeutic discoveries for patients suffering from a broad range of brain disorders, including Alzheimer s disease. We sought to understand the following: Whether our peers felt target identification and validation is lagging in comparison to other therapeutic areas such as metabolic disorders, infectious disease, and oncology. Is the lack of clear regulatory pathways off-putting? Are recent failures in research causing uncertainty, has a prior failure truly tested a hypothesis? Funding is there a lack of financial backing for neuroscience research in general? Question 2 Uncertainty/risk 19% AAIC 2017 Regulatory review and approval 12% N = PERSON SKIPPED Funding 17% Target identification/ validation 70% More than half of respondents were of the opinion that target identification was the foremost hurdle. Drug target identification is one of the most costly, labor-intensive and complex areas of drug development. The current main targets for Alzheimer s disease are amyloid, followed by inflammation and tau. However, improved understanding of the onset and progression of Alzheimer s disease will result in more efficient therapeutic approaches and expand potential targets. This opinion was mirrored in each respondent company grouping, most decisively within the Investigator/site sector (70%), followed by Pharma/biotech (64%). Page 4 of 9

6 QUESTION THREE: WHAT DO YOU BELIEVE IS THE MOST PROMISING THREAD OF ALZHEIMER S RESEARCH? (N=117, 2 SKIPPED) As a natural follow-on from question one, we asked our survey respondents to identify the strand of Alzheimer s disease research that they felt was most encouraging. Below follows a short explanation of the theories explored and an overview of their basic premise: Amyloid hypothesis - a microscopic protein fragment called beta-amyloid can accumulate in the brain, disrupting communication between brain cells and eventually killing them. Some researchers believe that flaws in the processes governing production, accumulation or disposal of beta-amyloid are the primary cause of Alzheimer s disease. Tau protein - abnormal aggregation of tau protein in the brain leads to the formation of tangles within nerve cells. In healthy areas, tau helps keep the transport system on track. But in areas where tangles are forming, the twisted strands of tau essentially disintegrate the transport system so that nutrients and other essential supplies can no longer move through the cells, which eventually die. Beta-secretase (BACE) closely related to the amyloid hypothesis, research into BACE inhibitors is currently ongoing, which, in theory would prevent build-up of beta-amyloid from forming. Hormonal research - changes in estrogen levels (for women and men) during aging may increase risk for Alzheimer s disease, use of selective estrogen receptor modulators (SERMs) to improve cognition, and studies of genetic risk factors could hold promise. Inflammation a mitochondrial protein, TSPO, accumulates in the inflamed brain under conditions that activate microglia. Along with amyloid, this protein is increased in the brains of people with Alzheimer s disease. 5-HT6 receptor the 5-HT6 receptor is a subtype of 5-HT receptor that binds serotonin. 5-HT6 antagonists improve cognition, learning, and memory, agents such as idalopirdine and intepirdine are being developed as novel treatments for Alzheimer s disease and other forms of dementia. Feedback received from survey participants was to consider lifestyle factors as an addition to this category. On the final day of the AAIC conference The Lancet presented data which suggested one in three cases of dementia could be prevented by addressing nine lifestyle factors, including increase in education, physical activity and social contact. Page 5 of 9

7 Question 3 Tau protein 31% Inflammation 27% AAIC 2017 N = PEOPLE SKIPPED 5HT6 6% Beta-secretase (BASE) 5% Hormonal research 5% Amyloid hypothesis 43% Respondents were largely still confident in the amyloid hypothesis, within each company grouping the amyloid hypothesis garnered 35%-45% of the vote. Despite failures for amyloidtargeting compounds over the last year, some experts believe that the solution is to target the disease earlier, focusing on mild-moderate patients or prodromal subjects. QUESTION FOUR: WHAT DO YOU BELIEVE COULD IMPACT RECRUITMENT OF PRODROMAL ALZHEIMER S SUBJECTS IN A POSITIVE WAY? (N=117, 2 SKIPPED) Having identified that the amyloid hypothesis is still a very valid line of research and that the key to a cure or disease modifying treatment could stem from targeting patients at the earliest possible stage, recruitment of early onset and prodromal subjects has never been so important. The Alzheimer s Association recently identified that as many as 50,000 patients are required to support current research. Patients with Mild Cognitive Impairment (MCI) or prodromal subjects are often difficult to recruit, in part, due to biomarker eligibility requirements which may include PET imaging and/or cerebrospinal fluid assessments. Screening of subjects is therefore costly and time-consuming, with a significant screen fail rate. We wanted to find out what our peers felt could help increase prodromal subject recruitment and offered the following options: Interacting with online patient communities Digital screening of potential subjects with self-reported cognitive symptoms Pre-screening in the community Streamlining site visits combined with virtual reporting tools 60/40 alternate allocation ratio towards active treatment Page 6 of 9

8 Question 4 Pre-screening in the community 59% 60/40 alternate allocaion ratio towards active treatment 6% AAIC 2017 N = PEOPLE SKIPPED Streamlining site visits combined with virtual reporting tools 11% Digital screeening of potential subjects with self-reported cognitive symptoms 17% Interacting with online patient communications 24% Across all company types, pre-screening in the community was the most popular response. This would perhaps entail recruiting subjects via advertisements for people with memory problems or even depression. Several respondents also commented whilst at our booth that combining pre-screening in the community with materials on the positive societal impact of research participation could also be helpful. QUESTION FIVE: WHAT DO YOU FEEL ARE THE MAIN BARRIERS TOWARD PARTICIPATION IN ALZHEIMER S TRIALS? (PICK THE 3 MOST IMPORTANT) (N=117, 2 SKIPPED) To mobilize subjects to take part in clinical trials it is very important for researchers to understand the barriers preventing people from participation in Alzheimer s disease studies. We identified the following as factors which may obstruct a person from considering taking part in clinical research: Low trial awareness Comorbidities Concomitant medications Risks of side effects Barriers associated with procedures (eg. unwillingness to undergo procedures such as lumbar puncture) Risk of placebo Page 7 of 9

9 Travel and other logistics Informed consent We allowed survey participants to select up to three answers and therefore have recorded the answers to this question by instances of response. Question 5 Risk of side effects 30% Travel and other logistics 27% Low trial awareness 41% AAIC 2017 N = PEOPLE SKIPPED Comorbidities 25% Concomitant medications 25% Barriers associated with procedures (unwillingness to undergo procedures such as lumbar puncture 38% Risk of placebo 16% Informed consent 5% Overall, we saw that low trial awareness was the most popular response, however, we did not see the same unanimity among respondent groups as with other questions posed. Whilst the Investigator/site and Pharma/biotech groups agreed that low trial awareness was the key obstructive factor to research participation. The smaller CRO and Service/product provider to the industry groups were not as certain. Whilst identifying low trial awareness as a primary factor, they also identified barriers associated with procedures and travel/logistics as equally important. Within the CRO group barriers associated with procedures was identified as the main factor preventing potential volunteers participating in clinical trials. Page 8 of 9

10 QUESTION SIX: DO YOU BELIEVE THAT A DISEASE MODIFYING DRUG FOR ALZHEIMER S WILL HAVE BEEN DISCOVERED BY TARGET 2025? (N=116, 3 SKIPPED) G7 leaders have pledged to find a cure or disease-modifying treatment for Alzheimer s disease by We decided to end our survey with a general question on whether our survey respondents felt that this was achievable. 71% of all respondents were hopeful that this was the case, in all respondent groups the majority leaned toward an optimistic response. Question 6 Yes 71% No 29% 0% 10% 20% 30% 40% 50% 60% 70% 80% N = 116 (3 skipped) EXTERNAL SOURCES: Alzheimer s Research UK Alzheimer s Association Brightfocus Foundation Page 9 of 9