Rare Disease & Orphan Drug Research

We have extensive experience in supporting orphan drugs for various rare diseases, including rare cancers, ultra-rare genetic disorders, metabolic diseases, neurological diseases, and autoimmune diseases. We have a deep understanding of the unique challenges (e.g., limited data, heterogeneous and multi-organ impacts, small populations, growing pricing pressure and competition) and opportunities (e.g., high unmet needs, opportunities for accelerated approval, extended market exclusivity) associated with rare disease research. In this work, we have used a variety of data sources including registries, clinical trials, chart reviews, global academic collaborations, and administrative data.

Our research for rare diseases has included:

  • Support for orphan designations via epidemiological studies (e.g., estimating prevalence) and establishing expected relative benefit
  • Characterizing natural history data and providing consultation on clinical trial designs 
  • Supporting and presenting at joint FDA/industry workshops to address challenges in bringing rare disease drugs to market
  • Incorporation of real-world evidence (RWE) and external controls in clinical regulatory submissions
  • Evaluating the burden of rare diseases and conducting comparative analysis
  • Developing health economic models and supporting global Health Technology Assessment (HTA) submissions 
  • Conducting HEOR planning and strategy development 
  • Collaborating with rare disease foundations on registry design, patient and caregiver surveys, and database analyses
  • Developing and validating instruments for measuring patient-reported outcomes (PROs) and health care resource use 

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Selected Examples of Our Work

  • Karam C, Brown D, Yang M, Done N, Zhu JJ, Greatsinger A, Bozas A, Vera-Llonch M, Signorovitch J. Long-term treatment effects of inotersen on health-related quality of life in patients with hATTR amyloidosis with polyneuropathy: Analysis of the open-label extension of the NEURO-TTR trial. Muscle Nerve. 2022 Oct;66(4):438-446. doi: 10.1002/mus.27675. Epub 2022 Aug 4.
  • Maurer MS, Dunnmon P, Fontana M, Quarta CC, Prasad K, Witteles RM, Rapezzi C, Signorovitch J, Lousada I, Merlini G. Proposed Cardiac End Points for Clinical Trials in Immunoglobulin Light Chain Amyloidosis: Report From the Amyloidosis Forum Cardiac Working Group. Circ Heart Fail. 2022 Jun;15(6):e009038.
  • Muntoni F, Signorovitch J, Sajeev G, Goemans N, Wong B, Tian C, Mercuri E, Done N, Wong H, Moss J, Yao Z, Ward SJ, Manzur A, Servais L, Niks EH, Straub V, de Groot IJ, McDonald C; North Star Clinical Network, PRO-DMD-01 Study, The Association Française contre les Myopathies (AFM), The DMD Italian Group, and The Collaborative Trajectory Analysis Project (cTAP). Real-world and natural history data for drug evaluation in Duchenne muscular dystrophy: suitability of the North Star Ambulatory Assessment for comparisons with external controls. Neuromuscul Disord. 2022 Apr;32(4):271-283.
  • Goemans N, Signorovitch J, Sajeev G, Yao Z, Gordish-Dressman H, McDonald CM, Vandenborne K, Miller D, Ward SJ, Mercuri E; investigators from PRO-DMD-01 Study, CINRG DNHS, ImagingDMD, and the DMD Italian Group. Suitability of external controls for drug evaluation in Duchenne muscular dystrophy. Neurology. 2020 8;95(10):e1381-e1391.
  • Ho CY, Day SM, Ashley EA, Michels M, Pereira AC, Jacoby D, Cirino AL, Fox JC, Lakdawala NK, Ware JS, Caleshu CA, Helms AS, Colan SD, Girolami F, Cecchi F, Seidman CE, Sajeev G, Signorovitch J, Green EM, Olivotto I. Genotype and Lifetime Burden of Disease in Hypertrophic Cardiomyopathy: Insights from the Sarcomeric Human Cardiomyopathy Registry (SHaRe). Circulation. 2018 Oct 2;138(14):1387-1398.
  • Tzellos T, Yang H, Mu F, Calimlim B, Signorovitch J. Impact of hidradenitis suppurativa on work loss, indirect costs and income. Br J Dermatol. 2019 Jul;181(1):147-154.
  • Song J, Swallow E, Said Q, Peeples M, Meiselbach M, Signorovitch J, Kohrman M, Korf B, Krueger D, Wong M, Sparagana S. Epilepsy treatment patterns among patients with tuberous sclerosis complex. J Neurol Sci. 2018 Aug 15;391:104-108.
  • Nazareth T, Li N, Marynchenko M, Zhou Z, Chopra P, Signorovitch J, Wu E, Ahmed S, Marvel J, Sasane R. Burden of illness among patients with fragile X syndrome (FXS): a Medicaid perspective. Curr Med Res Opin. 2016;32(3):405-16.
  • Kimball AB, Jemec GB, Yang M, Kageleiry A, Signorovitch JE, Okun MM, Gu Y, Wang K, Mulani P, Sundaram M. Assessing the validity, responsiveness and meaningfulness of the Hidradenitis Suppurativa Clinical Response (HiSCR) as the clinical endpoint for hidradenitis suppurativa treatment. Br J Dermatol. 2014 Dec;171(6):1434-42.
  • Quittner AL, Zhang J, Marynchenko M, Chopra PA, Signorovitch J, Yushkina Y, Riekert KA. Pulmonary medication adherence and health-care use in cystic fibrosis. Chest. 2014 Jul;146(1):142-151.
  • Sawicki GS, Ayyagari R, Zhang J, Signorovitch JE, Fan L, Swallow E, Latremouille-Viau D, Wu EQ, Shi L. A pulmonary exacerbation risk score among cystic fibrosis patients not receiving recommended care. Pediatr Pulmonol. 2013 Oct;48(10):954-61.
  • Sawicki GS, Signorovitch JE, Zhang J, Latremouille-Viau D, von Wartburg M, Wu EQ, Shi L. Reduced mortality in cystic fibrosis patients treated with tobramycin inhalation solution. Pediatr Pulmonol. 2012 Jan;47(1):44-52.
  • Jordan L, Adams-Graves P, Kanter-Washko J, Oneal PA, Sasane M, Vekeman F, Bieri C, Magestro M, Marcellari A, Duh MS. Multicenter COMPACT Study of COMplications in Patients with Sickle Cell Disease and Utilization of Iron Chelation Therapy. Curr Med Res Opin. 2014 Dec 31:1–11.
  • Strosberg JR, Benson AB, Huynh L, Duh MS, Goldman J, Sahai V, Rademaker AW, Kulke MH. Clinical Benefits of Above-Standard Dose of Octreotide LAR in Patients with Neuroendocrine Tumors for Control of Carcinoid Syndrome Symptoms: A Multicenter Retrospective Chart Review Study. Oncologist. 2014 Sep;19(9):930–936.
  • Carlozzi NE, Victorson D, Sung V, Beaumont JL, Cheng W, Gorin B, Duh MS, Samuelson D, Tulsky D, Gutierrez S, Nowinski CJ, Mueller A, Shen V, Frank S. HD-PRO-TRIAD™ Validation: A Patient-Reported Instrument for the Symptom Triad of Huntington’s Disease. Tremor Other Hyperkinet Mov. 2014 Apr 14;4:223.
  • Truong HL, Nellesen D, Ludlam WH, Neary MP. Budget Impact of Pasireotide for the Treatment of Cushing’s Disease, a Rare Endocrine Disorder Associated with Considerable Comorbidities. J Med Econ. 2014 Apr;17(4):288–295.
  • Garrison LP Jr, Wang ST, Huang H, Ba-Mancini A, Shi H, Chen K, Korves C, Dhawan R, Cakana A, van de Velde H, Corzo D, Duh MS. The Cost-Effectiveness of Initial Treatment of Multiple Myeloma in the US with Bortezomib Plus Melphalan and Prednisone Versus Thalidomide Plus Melphalan and Prednisone or Lenalidomide Plus Melphalan and Prednisone with Continuous Lenalidomide Maintenance Treatment. Oncologist. 2013; 18(1):27–36. 
  • Kakkis ED, Signorovitch J. The Randomized Blind Start Trial: A New Study Design to Assess Clinical Outcomes in Rare, Heterogeneous Patient Populations. 12th International Congress of Inborn Errors of Metabolism (ICIEM), Barcelona, Spain, 3-6 September 2013. (Poster).
  • Chen L, Guérin A, Xie J, Wu EQ, Yu AP, Ericson SG, Jabbour E. Monitoring and Switching Patterns of Patients with Chronic Myeloid Leukemia Treated with Imatinib in Community Settings: A Chart Review Analysis. Curr Med Res Opin. 2012 Nov; 28(11):1831–1839. Epub date 2012 Nov 5.

Selected Examples of Our Work