Background Eliglustat is a first-line oral treatment for adults with Gaucher disease type 1 who have an extensive, intermediate or poor CYP2D6 metabolizer phenotype (> 90% of patients). Whereas enzyme replacement therapy for Gaucher disease has been widely used for more than two decades, eliglustat has only been in commercial use since 2014. Clinicians and patients want to better understand which adverse events are most commonly associated with eliglustat, as well as their severity, frequency, and duration. Methods This pooled analysis of treatment-emergent adverse events combines data from four completed eliglustat clinical trials involving 393 Gaucher disease type 1 patients. It represents 1400 patient-years of eliglustat exposure and a mean treatment duration of 3.6 years (maximum: 9.3 years). Results Eighty-one percent of patients remained in their respective trial until commercial availability of eliglustat (US patients only) or until trial completion. Nine patients (2.3%) withdrew from their respective trial due to one or more adverse events reported as eliglustat treatment-related; all but one of these events were mild or moderate. Overall, 97% of adverse events were mild or moderate and 86% were reported by the investigator as unrelated to eliglustat treatment. The overall rate of adverse events decreased over time and did not increase with increasing eliglustat dose. We evaluated frequency, duration, and severity of 14 adverse event terms reported at least once as treatment-related in 2% or more of all patients: dyspepsia (5.9%), headache (5.3%), abdominal pain upper (5.1%), dizziness (5.1%), diarrhea (4.6%), nausea (4.6%), arthralgia (3.6%), constipation (3.3%), abdominal pain (2.8%), gastroesophageal reflux disease (2.8%), fatigue (2.8%), palpitations (2.8%), abdominal distension (2.5%), and gastritis (2.3%). For abdominal pain upper, diarrhea, nausea, abdominal pain, and headache events, median duration was less than 14 days. All 14 adverse event terms, except for arthralgia and headache, were reported only once per patient in more than 70% of patients experiencing the event. Conclusions This final pooled analysis of treatment-emergent adverse events reinforces the favorable safety profile of eliglustat. The majority of the most frequently reported treatment-related adverse events were mild or moderate, transient, and occurred only once per patient. Electronic supplementary material The online version of this article (10.1186/s13023-019-1085-6) contains supplementary material, which is available to authorized users.

The objective of this review is to summarize the pharmacology, efficacy, and safety of cerliponase alfa for the treatment of late infantile neuronal ceroid lipofuscinosis type 2 (CLN2). Cerliponase alfa is recombinant human tripeptidyl peptidase 1 enzyme replacement therapy. A phase 1/2 trial established the efficacy and safety of cerliponase alfa for treatment of neuronal ceroid lipofuscinosis type 2. Treatment with intracerebroventricular cerliponase alfa resulted in slower decline of motor and language functions compared with natural history controls. Common adverse events include convulsions, electrocardiography abnormalities, pyrexia, vomiting, and upper respiratory tract infections. Intracerebroventricular device–related adverse events also occur. Cerliponase alfa is the first therapy for neuronal ceroid lipofuscinosis type 2 that targets the disease etiology. Cerliponase alfa is effective in delaying the progression of motor language decline for patients with neuronal ceroid lipofuscinosis type 2.

Gaucher disease type 1 (GD1) is an inherited lysosomal storage disorder caused by deficient enzymatic activity of acid β‐glucosidase, resulting in accumulation of its substrate glucosylceramide, leading to debilitating visceral, hematologic, and skeletal manifestations. Women with GD1 are at increased risk for complications during pregnancy, delivery, and postpartum. Treatment with enzyme replacement therapy is generally recommended before and during pregnancy to reduce risks. Eliglustat, an oral substrate‐reduction therapy, is a first‐line treatment for adults with GD1 adults who have extensive, intermediate, or poor CYP2D6‐metabolizer phenotypes (>90% of patients). We report on pregnancy outcomes among women in eliglustat trials who had unplanned pregnancies and female partners of men in the trials. In four phase 2 and 3 eliglustat trials of 393 adults with GD1, women of childbearing potential were required to use contraception, have monthly pregnancy tests, and discontinue eliglustat promptly if pregnant. In phase 2 and 3 trials, 18 women had 19 pregnancies, resulting in 14 healthy infants from 13 pregnancies (one set of twins), three elective terminations, one ectopic pregnancy, one spontaneous abortion, and one in utero death. Median estimated eliglustat exposure duration during pregnancy was 38 days. In phase 1 trials (non‐GD1 subjects), one woman had a spontaneous abortion. Partners of 16 eliglustat‐treated men with GD1 had 18 pregnancies, all resulting in healthy infants. Eliglustat is not approved during pregnancy due to limited data. Guidelines for clinicians and patients with GD that address use of eliglustat in women of childbearing potential are needed.

Introduction Approved in 1994 and assigned the International Nonproprietary Name (INN) imiglucerase by the World Health Organization, Cerezyme ® (Sanofi Genzyme) is an enzyme replacement therapy used to treat Gaucher disease in > 90 countries. At least two therapies approved outside the USA and the European Union, Abcertin ® and Asbroder ® , have adopted the identical INN imiglucerase. Both drugs were approved via regulatory pathways not aligned with World Health Organization Similar Biotherapeutic Product guidelines. Objective We analyzed whether the use of the identical INN "imiglucerase" for these drugs impacts adverse event (AE) reporting in the Sanofi Global Safety Database. Methods First, we reviewed all imiglucerase individual case safety reports (referred to as cases) including AE data reported between January 2012 and March 2018 that contained Abcertin or Asbroder in the narrative. In a second analysis, we examined cases from Mexico reported between May 2013 and March 2018 to assess changes in imiglucerase reporting following the 2015 approval of Asbroder in Mexico. Results Fifty-six cases mentioning Asbroder and none mentioning Abcertin were retrieved in the first analysis. Upon close review, the AEs of 45 cases (80.4%) were attributed to Asbroder, one (1.8%) to Cerezyme; the specific drug attribution for the AEs of ten cases (17.9%) could not be determined. In the second analysis, a substantial increase in cases and AEs was observed in the period after Asbroder approval (73 cases with 150 AEs pre-approval vs 132 cases with 333 AEs postapproval). Twenty-three of 132 (17.4%) post-approval cases reported discontinuation of treatment (19 related to Asbroder AEs, and four related to Cerezyme AEs). Infusion-associated reactions occurred in 25/132 cases (17 Asbroder related, six Cerezyme related, two indeterminate). Conclusions This analysis demonstrates two potential consequences of identical INN use between Cerezyme and Asbroder:(1) an aggregate safety profile for Cerezyme that includes other products using the identical INN leading to inaccurate pharmacovigilance data and (2) healthcare providers switching, substituting, or potentially assuming interchangeability between the products. Identical INN use without the brand name differentiator may compromise pharmacovigilance data, potentially masking differences in safety profiles between products.