In November 2017, the National Institute for Health and Care Excellence (NICE) recommended Strimvelis (GlaxoSmithKline), a gene therapy for a form of severe combined immunodeficiency (SCID).
Although the therapy is priced at €594,000, NICE expects value for the money
. Value is assessed relative to stem-cell transplantation, which is also expensive, requires a matched donor and carries risk of graft versus host disease
. The acute nature of SCID and its limited and expensive treatment options made it an excellent early candidate for gene therapy. However, manufacturers of immunoglobulin replacement therapy (IVIG) for less acute common variable immunodeficiency (CVID) should take note. Very high lifetime IVIG costs with suboptimal outcomes may ultimately make gene therapy viable economically (if not economically necessary) for CVID.
Superior Strimvelis outcomes with a background of electronic health record analytical tools and inexpensive whole-genome sequencing should green-light a paradigm shift in timely CVID diagnosis and identification of the root cause. This should be fertile ground for a revolutionary age of gene therapy solutions for CVID.
In the United States, four million newborns are screened annually for SCID, a disease estimated to occur in one of every 58,000 births
. Screening has advanced early intervention, prior to infections
. US trials for Strimvelis are planned and, assuming that results are consistent with past trials, it should become a standard of care. Treatment of CVID, which has a much higher prevalence (one in 25,000) may seem less urgent, but it is not
. CVID often goes undiagnosed for years, and children and young adults may suffer recurrent sinusitis, bronchitis and pneumonia, as well as eye, ear and other infections
. Before diagnosis and treatment, many people have already developed permanent respiratory, hearing or visual impairment, or cancer
The IVIG treatment regimen is time-consuming, inconvenient, very expensive and not completely effective. In the US, a single, monthly infusion may cost $9,000 ($8,000 for the product and $1,000 for infusion costs)
. A teenager aged 15 years at diagnosis surviving to age 75 years (assuming no price increases or disease-related complications) will incur $6.5m of lifetime infusion costs. The average cost is, however, much greater because the price of IVIG has continuously risen, hospitalisations are common, and quality of life and productivity are negatively affected.
With current and emerging technology, the days of lifetime IVIG infusions for CVID should be numbered. CVID is an enormous economic and public health burden. Now is the time for the pharmaceutical industry to fully embrace gene therapy and partner with health systems, genetic diagnostic centres, research institutions and regulators to lead the way in developing gene therapy cures for CVID.
Masters student in public health
Milken Institute School of Public Health, George Washington University
 National Institute for Health and Care Excellence. Evaluation consultation document: Strimvelis for treating adenosine deaminase deficiency–severe combined immunodeficiency. Available at: https://www.nice.org.uk/guidance/gid-hst10005/documents/evaluation-consultation-document (accessed December 2017)
 Mulin E. A year after approval, gene-therapy cure gets its first customer. MIT Technology Review. 3 May 2017. Available at: https://www.technologyreview.com/s/604295/a-year-after-approval-gene-therapy-cure-gets-its-first-customer/ (accessed December 2017)
 Immune Deficiency Foundation. Questions about severe combined immunodeficiency disease. Available at: https://primaryimmune.org/wp-content/uploads/2014/08/questions-about-SCID.pdf (accessed December 2017)
 Immune Deficiency Foundation. Common variable immunodeficiency. Available at: https://primaryimmune.org/about-primary-immunodeficiencies (accessed December 2017)
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 National Institutes of Health, US National Library of Medicine, Genetics Home Reference. Common variable immune deficiency. Available at: https://ghr.nlm.nih.gov/condition/common-variable-immune-deficiency (accessed December 2017)