ABOUT CURE Citizens United for Research in Epilepsy (CURE) is a nonprofit organization dedicated to finding a cure for epilepsy by raising funds for research and by increasing awareness of the prevalence and devastation of this disease.

STATE OF EPILEPSY RESEARCH 2010

LETTER FROM THE CHAIR Dear Friends, As Chair of CURE and a member of the epilepsy community, I am at once dismayed and hopeful as we publish our first annual State of Epilepsy Research Report. In the pages that follow, you will find our first attempt to assess our community’s collective progress toward a cure for epilepsy. I am dismayed because as I read through this report, the enormous challenges we face in advancing this field crystallize. The data confirms that funds for epilepsy research—from government, industry, and private sources—are totally insufficient given the magnitude of the problem and the status of our progress in the field. We know now that the vast majority of funding goes to incremental improvements in anticonvulsant medications (which are largely ineffective for about 40% of patients) rather than to uncovering underlying mechanisms that may lead to cures. We also know that the number of basic researchers in epilepsy is declining and that those involved have been less collaborative than their colleagues in other neurological disorders.

But, we also have great reason for hope. While our challenges are significant, I have every confidence that, as a community, we have the will and determination it takes to make meaningful progress toward defeating this disease. We are finally making strides in our efforts to communicate well beyond our community the critical importance and urgency of the need. This gives me tremendous faith that together we can turn the challenges detailed in this report into opportunities to make a real difference for our patients and loved ones. It is within our power to make this happen, but we must act now. Lives are being ravaged and lost every day that we delay. I have tremendous hope that these reports in coming years will tell the stories of great progress toward our common goal—a cure. Sincerely,

Susan Axelrod Chair

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STATE OF EPILEPSY RESEARCH 2010

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SUMMARY OF THE STATE OF EPILEPSY RESEARCH To assess the state of epilepsy research, we examined progress toward a cure across three areas: financial capital, research focus, and human capital and scientific collaboration. Our analyses have uncovered some concerning facts: (1) epilepsy research is significantly underfunded, (2) over three quarters of epilepsy research is focused on improving symptoms versus uncovering the underlying mechanisms of the disease, and (3) epilepsy researchers are declining in number and are less collaborative than researchers in other neurological disorders. From these observations, we believe a few imperatives become clear. At a minimum, funding of epilepsy research must increase. Additionally, given the poor understanding of mechanisms, we, as a community, must focus more on basic discovery research. Finally, to give ourselves the best chance at a cure, we must go out of our way to demand and facilitate collaboration among researchers.

EPILEPSY RESEARCH IS IN NEED OF MORE FUNDING In total, and per patient, epilepsy research is significantly underfunded from three major sources: pharmaceutical companies, the government, and private foundations. Pharmaceutical investment in epilepsy is less than in Alzheimer’s and Parkinson’s, and given the lack of early stage clinical programs, it is projected to decline further over the next several years. The government invests $140–160 million in EXHIBIT 1 Total research funding per patient in US, 20081 USD epilepsy research, but per patient contributes less to 2,000–2,500 epilepsy than it does to other major neurological disorders. Finally, at less than $10 million, 900–1,200 non-profit foundations contribute 620–760 500–590 less than $4 per patient to epilepsy research. Parkinson’s, by contrast, receives $40–50 per Alzheimer’s Parkinson’s Autism Epilepsy patient from nonprofits. All told, disease disease epilepsy receives less total funding per patient than Alzheimer’s, Parkinson’s, and autism (Exhibit 1). Per researcher, funding for epilepsy lags average funding for all diseases by nearly 50%. It is hard to imagine finding a cure (or cures) for epilepsy will be feasible without a significant increase in funding across all three sources. In particular, much can be done to drive an increase in contributions to epilepsy organizations for research, where the gap is most significant relative to other neurological disorders.

STATE OF EPILEPSY RESEARCH 2010

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STATE OF EPILEPSY RESEARCH 2010

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RESEARCH ON UNDERLYING MECHANISMS IS NEEDED Our research efforts should be re-balanced to focus more on the underlying mechanisms of epilepsy. Today, we focus 75–80% of our research on better controlling outcomes, such as seizure frequency and severity (Exhibit 2). Despite this allocation, only incremental improvements have been made to marketed antiEXHIBIT 2 Estimated epilepsy research allocation2 Percent of total research funding convulsants in the last ten years, with 40% of patients refractory to treatment and up to 60,000 Understanding causes 20–25 deaths occurring annually due to and mechanisms seizure-related causes. The mechanisms of epilepsy are 75–80 clearly not well understood. An Managing outcomes increased focus on basic discovery—today only 20–25% of research—is required if we hope to someday find a true cure. Increasing epilepsy research investments from government and private foundations—the largest funders of underlying mechanism research today—is the best way to achieve this goal.

GREATER SCIENTIFIC COLLABORATION IS REQUIRED Epilepsy authors have 60% fewer “links,” or co-authorships, than authors in Parkinson’s, indicating lower levels of collaboration Number of authors and links by disease6

EXHIBIT 3 Number of authors Number of links

Epilepsy

1,230 6,590

+60% Parkinson’s

1,109 10,560

Leading researchers across institutions consistently claim that lack of collaboration among researchers is the number one obstacle to finding a cure for epilepsy. We compared collaboration among epilepsy researchers—as measured by co-authorship of research studies—to collaboration in other severe neurological disorders. Our findings confirmed that

STATE OF EPILEPSY RESEARCH 2010

epilepsy researchers collaborate less than those researching Parkinson’s and Alzheimer’s (Exhibits 3, 4). Often the greatest insights are made when researchers from different institutions or disciplines work together. Research funders can drive collaboration through grant criteria that require active engagement from multiple institutions or disciplines, and by creating forums for sharing positive and negative data, specimen repositories, and research discussion roundtables. Using “network mapping,” a way to map co-authorship on publications within a disease area, we can see that authors in epilepsy collaborate less than those in Parkinson’s6 Low betweenness*

Higher betweenness*

Co-authorship, rare

EXHIBIT 4

Co-authorship, frequent

Epilepsy network map More independent branches indicate fragmented research activity

Parkinson’s network map High density (dark green) of network highlights increased collaboration

* “Betweenness” measures how many researchers are connected through the same “middleman”

It is the recognition of both the successes and shortcomings described in this report that will allow us as a community to accelerate progress toward a cure.

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STATE OF EPILEPSY RESEARCH 2010

NOTES

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STATE OF EPILEPSY RESEARCH 2010

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STATE OF EPILEPSY RESEARCH DASHBOARD FINANCIAL BACKING

RESEARCH IN EPILEPSY

Parkinson’s

Alzheimer’s Autism

Epilepsy

Research $ spent per patient1

2004–2009 Research focus2 Percent of total

40 -50

Private

Government

Pharmaceutical

7-9

40 -60

3-4

150 -170

91 -96

220 -260

56 -64

1,800 -2,300

800 -1,000

360 -440

440 -520

CLINICAL PIPELINE Alzheimer’s Autism

75–80 1,856

Number of articles3

66%

Percent of epilepsies with unknown cause4

2004–2009 Collaboration6 Number of co-authorship links

Phase I

20

54

1

5

Phase II

18

41

0

2

Phase III

10

16

2

11

4

11

1

16

4

3

0

5

Parkinson’s

10,560

Alzheimer’s

7,371

Autism

6,331

Epilepsy

6,590

2009

EPIDEMIOLOGY Prevalence (Number of

Treatment

Epilepsy

Drug development by phase5 Number of compounds

Approved

20–25

SCIENTIFIC COMMUNITY

Parkinson’s

Filed

Underlying mechanism

Low people)7

Incidence (Number of people per year)8 Mortality (Number of deaths per

year)9

Child mortality (Number of people under age 19 who die each year) Refractory (Percent of all people with

epilepsy)10

High

2.4 M

3.0M

150,000

200,000

41,000

61,000

NA

NA

40%

53%

Many critical facts are either completely unknown or available only in wide ranges

STATE OF EPILEPSY RESEARCH 2010

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END NOTES 1. Research funding per patient • Non-profit foundation funding. Sources: Foundation Directory Online (http://fconline.foundationcenter.org), Foundation Center, 2009; and individual foundation financial statements from 2007 and 2008. Methodology: used foundation contributions to research; applied ranges to account for assumptions. • Government funding. Sources: Research Portfolio Online Reporting Tool (http://report.nih.gov/rcdc/categories), National Institutes of Health, 2009. Methodology: Assumed total government funding is 5-10% higher than funding from NIH (e.g., Department of Defense). • Pharmaceutical funding. Sources: Joseph A. DiMasi, Ph.D., Impact Report, Tufts University Center for the Study of Drug Development, March 2007; Evaluate, 2008. Methodology: Assumed 40-50% of total R&D spending is attributed to development; determined annual development cost by calculating average cost per year, per phase of development, multiplied by the number of compounds currently in each development phase. • Prevalence of neurological disorders in the United States, sources: − Epilepsy. There is no definitive source. This report uses the Centers for Disease Control and Prevention (http://www.cdc.gov/epilepsy) which estimates prevalence at 2.5 million to 2.7 million. The National Institutes of Health estimates prevalence at 3 million (http://www.ninds.nih.gov/disorders/epilepsy/Curing_Epilepsy_Brochure.pdf). The CDC also reported in a 2008 study that 1% of non-institutionalized adults in the U.S. have epilepsy. This report did not include those most severely impacted, children, and those living in non-traditional homes. (http://www.cdc.gov/mmwr/preview/mmwrhtml/ss5706a1.htm?s_cid=ss5706a1_e) − Morbidity and Mortality Weekly Report. − Parkinson’s Disease. Estimate: 1.0 million. Parkinson’s 101 (http://www.michaeljfox.org/living_aboutParkinsons_parkinsons101. cfm#q1); Michael J. Fox Foundation, 2009. − Alzheimer’s Disease. Estimate: 4.5 million. Alzheimer’s Disease Fact Sheet (http://www.nia.nih.gov/NR/rdonlyres/7DCA00DB1362-4755-9E87-96DF669EAE20/11209/84206ADEARFactsheetAlzDiseaseFINAL08DEC23.pdf), National Institutes of Health, 2008. − Autism. Estimate: 0.5 million. Autism Spectrum Disorders (http://www.nimh.nih.gov/health/publications/autism/completeindex.shtml), National Institutes of Health, 2008. 2. Epilepsy research allocation • Sources: Clinicaltrials.gov, 2008; Research Portfolio Online Reporting Tool (http://report.nih.gov/rcdc/categories/ProjectSearch.aspx? FY=2008&DCat=Epilepsy), National Institutes of Health, Jan 2004-July 2009. • Methodology: Selected a representative sample of clinical trials and NIH-funded research projects, calculated the weighted average for research on managing outcomes, based on contribution of funding from each source. 3. Number of articles published in epilepsy • Source: “Core Clinical Journals,” (PubMed, Jan 2004-Aug 2009). • Methodology: Due to the high number of authors, we included only those who have published two or more articles in past 5 years. 4. Percent of epilepsies with unknown causes • Source: Hauser, W. A., Annegers, J. F., Kurland, L. T. (1993). “Incidence of epilepsy and unprovoked seizures in Rochester, Minnesota,” 1935-1984. Epilepsia, 34(3), 453-468. 5. Drug development • Source: Evaluate, 2008 6. Research collaboration • Source: Ibid, Endnote No. 3 • Methodology: Assumed co-authorship as proxy for collaboration. “Links” represent the number of co-authorships between researchers. “Betweenness” measures how many researchers are connected through the same “middleman.” Researchers with high betweenness scores have a greater opportunity to connect other researchers. • Note: articles included references to epilepsy, but not related topics (e.g., tuberous sclerosis) 7. Prevalence of epilepsy • Source: Ibid, Endnote No. 1 8. Incidences of epilepsy • Sources: Sander, J.W., “The Epidemiology of Epilepsy Revisited,” Department of Clinical and Experimental Epilepsy, Institute of Neurology, University College London, Current Opinion in Neurology, 2003 (Pubmed,http://www.ncbi.nlm.nih.gov/pubmed/12644744); “Targeting epilepsy: Improving the Lives of People with One of the Nation’s Most Common Neurological Conditions,” Centers for Disease Control and Prevention, 2009 (http://www.cdc.gov/NCCdphp/publications/AAG/epilepsy.htm); U.S. population - U.S. Census Bureau (http://www.census.gov). 9. Mortality from epilepsy • Sources: Tomson, T., “Mortality in Epilepsy,” Department of Clinical Neuroscience, Karolinska Institute, Karolinska Hospital, Stockholm, Sweden, Journal of Neurology, 2000 (Pubmed, http://www.ncbi.nlm.nih.gov/pubmed/10701892?ordinalpos=1&itool= EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum); U.S. Mortality rates – National Vital Statistics Reports, Deaths: Final Data for 2006 (http://www.cdc.gov/nchs/FASTATS/deaths.htm), Centers for Disease Control and Prevention, 2006. • Methodology: Assumed mortality for patients with epilepsy two to three times higher than the average U.S. population 10. Refractory to at least one anti-convulsant • Sources: Therapeutic Category Outlook, S.G. Cowen & Co., Sept. 2008; “Early Identification of Refractory Epilepsy,” Kwan, P. and Brodie, M.J., University Department of Medicine and Therapeutics, Western Infirmary, Glasgow, Scotland, New England Journal of Medicine, Feb. 2000 (Pubmed, http://www.ncbi.nlm.nih.gov/pubmed/10660394). 11. Intractable to all anti-convulsants • Source: Therapeutic Category Outlook, S.G. Cowen & Co., Sept 2008.

2010 CURE Leadership Board of Directors Susan Axelrod, MBA, Chair Chicago, IL Barbara Kelly, Vice-Chair Oak Brook, IL Jeanne Donalty Utica, NY

Scientific Advisory Board Robert Fisher, MD, PhD Stanford School of Medicine Howard Goodkin, MD, PhD University of Virginia Medical School Jeffrey L. Noebels, MD, PhD Baylor College of Medicine

Thomas Hynes, JD, MBA Chicago, IL LeeAnn Brigido Lincoln, RI

Ivan Soltesz, PhD University of California, Irvine Karen S. Wilcox, PhD University of Utah

Gardiner Lapham, MPH, RN Washington, DC

Staff

Randolph Siegel, MBA New York, NY

Michelle Marciniak, MPH Executive Director Vicky Holets Whittemore, PhD Scientific Consultant Danielle Davis Program Officer

For more information on CURE: www.CUREepilepsy.org