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replacement therapy or experience anaphylactic reactions."
While this description is aligned with miglustat's label, it does
not apply to eliglustat, which is approved as a first-line therapy
for type 1 Gaucher disease.16,17 Eliglustat's efficacy in treatment-naive patients was demonstrated in the Phase 3
ENGAGE trial (NCT00891202), which is not cited in this
article's "Eliglustat Efficacy" section.18 In addition to this, the
authors state that comparisons between enzyme replacement
therapy and substrate reduction therapy are limited, despite the
fact that the Phase 3 ENCORE trial (NCT00943111) demonstrated noninferiority in patients switched from imiglucerase
to eliglustat, as cited elsewhere in the article.19 It should also
be noted that, since the publication of this review, data from
the ENCORE long-term extension have been released and
found that patients remained stable on eliglustat for up to 4
years of follow-up.20 Finally, the authors caution that "patients
who are ultra-rapid CYP2D6 metabolizers are not good candidates for eliglustat," but do not mention that ultra-metabolizers account for 2% to 5% of the population, a distribution that
was mirrored in eliglustat's clinical trial population.21,22 In
total, these statements mischaracterize the proportion of
patients that may benefit from eliglustat.
Finally, in both the abstract and conclusion, the authors
note that "there are no approved therapies for type 2 and type
3 disease." In fact, taliglucerase is approved in Canada for
"the hematological manifestations in pediatric patients with
a confirmed diagnosis of type 3 Gaucher disease."23 Also,
imiglucerase is approved for nonneurological manifestations
of type 3 disease in the European Union due to it having
effects beyond "symptom management," including improvement in anemia, thrombocytopenia, bone disease, and visceromegaly demonstrated in multiple studies.14,24
In summary, we respectfully request that your readership
be made aware of the inaccuracies and limitations described
above.
References
1. Van Rossum A, Holsopple M. Enzyme replacement or substrate reduction? A review of Gaucher disease treatment
options. Hosp Pharm. 2016;51(7):553-563.
2. Hospital Pharmacy. http://archive.hospital-pharmacy.com/.
Accessed July 6, 2017.
3. El-Beshlawy A, Tylki-Szymanska A, Vellodi A, et al. Longterm hematological, visceral, and growth outcomes in children
with Gaucher disease type 3 treated with imiglucerase in the
International Collaborative Gaucher Group Gaucher Registry.
Mol Genet Metab. 2017;120:47-56.
4. Charrow J, Andersson HC, Kaplan P, et al. The Gaucher registry: demographics and disease characteristics of 1698 patients
with Gaucher disease. Arch Intern Med. 2000;160:2835-2843.
5. Weinreb NJ, Deegan P, Kacena KA, et al. Life expectancy in
Gaucher disease type 1. Am J Hematol. 2008;83:896-900.
6. Pastores GM, Weinreb NJ, Aerts H, et al. Therapeutic goals in
the treatment of Gaucher disease. Semin Hematol. 2004;41:4-14.
7. VPRIV (velaglucerase) [package insert]. Lexington, MA:
Shire Human Genetic Therapies, Inc; 2015.

Hospital Pharmacy 52(11)
8. ELELYSO (taliglucerase) [packet insert]. New York, NY:
Pfizer Laboratories; 2014.
9. Cerezyme (imiglucerase) [package insert]. Cambridge, MA:
Genzyme Corporation; 2011.
10. Cox TM, Aerts JM, Belmatoug N, et al. Management of
non-neuronopathic Gaucher disease with special reference to
pregnancy, splenectomy, bisphosphonate therapy, use of biomarkers and bone disease monitoring. J Inherit Metab Dis.
2008;31:319-336.
11. Granovsky-Grisaru S, Belmatoug N, vom Dahl S, Mengel E,
Morris E, Zimran A. The management of pregnancy in Gaucher
disease. Eur J Obstet Gynecol Reprod Biol. 2011;156:3-8.
12. Sekijima Y, Ohashi T, Ohira S, Kosho T, Fukushima Y.
Successful pregnancy and lactation outcome in a patient with
Gaucher disease receiving enzyme replacement therapy, and
the subsequent distribution and excretion of imiglucerase in
human breast milk. Clin Ther. 2010;32:2048-2052.
13. Zimran A, Morris E, Mengel E, et al. The female Gaucher
patient: The impact of enzyme replacement therapy around
key reproductive events (menstruation, pregnancy and menopause). Blood Cells Mol Dis. 2009;43:264-288.
14. Cerezyme: EPAR Product Information. http://www.ema.
europa.eu/docs/en_GB/document_library/EPAR_-_Product_
Information/human/000157/WC500024112.pdf.
Published
2010. Accessed July 6, 2017.
15. Burrow TA, Grabowski GA. Velaglucerase alfa in the treatment
of Gaucher disease type 1. Clin Investig (Lond). 2011;1:285293.
16. Zavesca (miglustat) [package insert]. San Francisco, CA:
Actelion Pharmaceuticals US, Inc; 2014.
17. CERDELGA (eliglustat) [package insert]. Waterford, Ireland:
Genzyme Corporation, a Sanofi Company; 2014.
18. Mistry PK, Lukina E, Ben Turkia H, et al. Effect of oral eliglustat on splenomegaly in patients with Gaucher disease type 1:
the ENGAGE randomized clinical trial. JAMA. 2015;313:695706.
19. Cox TM, Drelichman G, Cravo R, et al. Eliglustat compared with imiglucerase in patients with Gaucher's disease
type 1 stabilised on enzyme replacement therapy: a phase 3,
randomised, open-label, non-inferiority trial. Lancet. 2015;
385:2355-2362.
20. Cox TM, Drelichman G, Cravo R, et al. Eliglustat maintains
long-term clinical stability in patients with Gaucher disease type
1 stabilized on enzyme therapy. Blood. 2017;129(17):23752383.
21. Hicks JK, Sangkuhl K, Swen JJ, et al. Clinical Pharmacogenetics
Implementation Consortium guideline (CPIC) for CYP2D6 and
CYP2C19 genotypes and dosing of tricyclic antidepressants:
2016 update. Clin Pharmacol Ther. 2017;102(1): 1532-6535.
doi:10.1002/cpt.597.
22. Peterschmitt MJ, Cox GF, Ibrahim J, et al. A pooled analysis of
adverse events in 393 adults with Gaucher disease type 1 from
four clinical trials of oral eliglustat: Evaluation of frequency,
timing, and duration. Blood Cells Mol Dis. 2017 Jan 13. pii:
S1079-9796(17)30025-6. doi:10.1016/j.bcmd.2017.01.006.
23. ELELYSO [package insert]. Kirkland, Quebec: Pfizer Canada,
Inc; 2016.
24. Sechi A, Deroma L, Dardis A, et al. Long term effects of
enzyme replacement therapy in an Italian cohort of type 3
Gaucher patients. Mol Genet Metab. 2014;113(3):213-218.

http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/000157/WC500024112.pdf http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/000157/WC500024112.pdf http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/000157/WC500024112.pdf http://archive.hospital-pharmacy.com/

Table of Contents for the Digital Edition of Hospital Pharmacy - December 2017