The ALPHA Project

• Identify knowledge gaps both in clinical care and research
• Create consensus around the fundamental pillars that are missing in the field and stalling drug development and progress
• Pave a path forward for more accurate and timelier diagnosis, greater access to care, and improved treatment options for people with lupus
• Result in an actionable, documented, and published roadmap that is meaningful and useful to everyone in the field, no matter where they are in the world

We know that the level and quality of data and research addressing issues related to lupus care, treatment, and healthcare access are not consistent across the global field. For example, there are differences in opinion when it comes to disease definition, treatment regiments, diagnostic criteria, and clinical trial design. The forum and opportunity to develop consensus around these issues had not existed.

This lack of consensus has led to a poor understanding about lupus, the inability to diagnose lupus in a timely fashion, especially by physicians with less experience in lupus, and a string of clinical trials of potential new treatments that failed to reach their primary endpoints and preventing them from being approved for use in treating lupus.

• Established a geographically and professionally diverse Global Advisory Committee (GAC) of lupus thought leaders to guide and oversee the study
• Conducted in-depth interviews to obtain further opinions and detailed rationale for the most urgent barriers in the field and access the level of existing agreement across the lupus expert community
• Conducted a global online survey of lupus experts focusing on the attitudes and perceptions about lupus and prioritization of the most pressing challenges to improve diagnosis, care, treatment and research
• Analyzed the survey results to identify and prioritize the barriers as ranked by the survey participants
• Global Advisory Committee has met and established next steps for addressing the identified barriers

Lupus heterogeneity (diversity of the disease and the many manifestations or ways that it can impact the body) was identified as the primary barrier impeding the development of clinically meaningful treatments, the advancement of clinical care, and improvements to access and value. The study validated known challenges in lupus, identifying the five top barriers to improving outcomes in lupus:

• Lack of diagnostic, predictive and prognostic biomarkers for lupus and deficiency of biomarkers to predict drug response in clinical trials;
• Flawed clinical trial design;
• Lack of access to clinicians familiar with lupus/limited awareness of lupus among non-expert medical professionals;
• Barriers to the effective management of lupus due to social determinants of care in predominantly lower socioeconomic status areas;
• And, lack of treatment adherence.

• Drug development: Update current lupus outcome measures and issuing a declarative consensus statement on steroid-sparing drugs.
• Clinical care: Lead the development of a consensus effort to define lupus. The new definition will build on current research definitions to include closely related immune-mediated inflammatory disorders, such as cutaneous variants. After establishing a consensus definition, it will be disseminated through publication and broader discussion.
• Access to care: Spearhead an effort to gain a better understanding of social determinants of health and contributors to health disparities, and investigate the unique access to care issues faced by children with lupus.
• Additional steps: Conduct an assessment of current biomarker development and data-sharing activities and identify gaps. The assessment will lead to the creation of standardized global data-sharing efforts and support international collective research collaborations.

The ALPHA team will continue to engage stakeholders and support further research endeavors to characterize key barriers and further explore and conceptualize the lupus spectrum. The next step will be for the Global Advisory Committee (GAC) to establish a task force to develop and implement the chosen solutions to each barrier to improve outcomes for people living with this very challenging and life-altering disease.

• Sang-Cheol Bae, MD, PhD, MPH | Hanyang University, South Korea
• Ian Bruce, MD, FRCP | University of Manchester, U.K.
• Erin Connolly-Strong, PhD | Mallinckrodt Pharmaceuticals, U.S.
• Karen Costenbader, MD, MPH | Brigham and Women’s Hospital, U.S.
• Brad Dickerson | Lupus and Allied Disease Association, Inc. U.S.
• Thomas Dörner, MD | Charité University, Germany
• Amy Kao, MD, MPH, MS | EMD Serono Research & Development Institute, Inc. (a business of Merck KGaA, Darmstadt, Germany)
• Sue Manzi, MD, MPH | Allegheny Health Network, U.S.
• Eric Morand, MBBS (Hons), FRACP, PhD | Monash University, Australia
• Sandra Raymond | Lupus Foundation of America, U.S.
• Brad Rovin, MD, FACP, FASN | Ohio State University, U.S.
• Laura Schanberg, MD | Duke University Medical Center, U.S.
• Joan Von Feldt, MD, MSEd | GlaxoSmithKline, U.S.
• Victoria Werth, MD | University of Pennsylvania and Philadelphia VAMC, U.S.

The ALPHA Project was launched in partnership with founding partner EMD Serono Research & Development, Inc. (a business of Merck KGaA, Darmstadt, Germany) and through additional support by GlaxoSmithKline.

The continued support and additional contributions of AstraZeneca and Lupus and Allied Diseases Association have made current Phase II efforts possible.