Safety and effectiveness of taliglucerase alfa in patients with Gaucher disease: an interim analysis of real-world data from a multinational drug registry (TALIAS)

Abstract

Background Limited real-world data from routine clinical care are available on the safety and effectiveness of treatment with taliglucerase alfa in patients with Gaucher disease (GD). Methods Taliglucerase Alfa Surveillance (TALIAS), a multinational prospective Drug Registry of patients with GD, was established to evaluate the long-term safety (primary objective) and effectiveness (secondary objective) of taliglucerase alfa. We present an interim analysis of the data from the Drug Registry collected over the 5-year period from September 2013 to January 2019. Results A total of 106 patients with GD (15.1% children aged < 18 years; 53.8% females) treated with taliglucerase alfa have been enrolled in the Drug Registry, as of January 7, 2019. The median duration of follow-up was 795 days with quartiles (Q1, Q3) of 567 and 994 days. Fifty-three patients (50.0%) were from Israel, 28 (26.4%) were from the United States, and 25 (23.6%) were from Albania. At the time of enrollment, most patients (87.7%) had received prior enzyme replacement therapy (ERT). Thirty-nine of the 106 patients had treatment-emergent adverse events (AEs). Twelve of the 106 patients experienced serious AEs; two patients experienced four treatment-related serious AEs. Four patients died, although none of the deaths was considered to be related to taliglucerase alfa treatment by the treating physicians. Nine patients discontinued from the study, including the four who died. At baseline, patients with prior ERT had a higher mean hemoglobin concentration and platelet counts than treatment-naïve patients, likely reflecting the therapeutic effects of prior treatments. During follow-up, the hemoglobin concentration and platelet counts increased in the treatment-naïve patients and remained relatively constant or increased slightly in patients with prior ERT. Spleen and liver volumes decreased in treatment-naïve patients. Conclusions The interim data showed no new or emergent safety signals. The overall interim data are consistent with the clinical program experience and known safety and effectiveness profile of taliglucerase alfa.

A review on Gaucher disease: therapeutic potential of β-glucocerebrosidase-targeted mRNA/saRNA approach

“…Indeed, treatment with imiglucerase demonstrated exceptional and long-lasting efficacy in GD1 patients while minimal toxicity was observed 116 . Other two ERTs- velaglucerase and taliglucerase have also demonstrated remarkable efficacy, safety, and long-lasting effects 117 , 118 . Despite the effectiveness of ERT, the treatment does have some limitations.…”

Twelve Years of the Gaucher Outcomes Survey (GOS): Insights, Achievements, and Lessons Learned from a Global Patient Registry

“…In contrast to clinical trials, which by definition are limited to small patient numbers in rare diseases, rare disease registries afford the opportunity to amass real-world longitudinal data from larger cohorts, including children, pregnant women, asymptomatic patients, and patients with neuronopathic GD, over longer time periods, while collection of cross-sectional registry data allow the reconstruction of natural histories, which would otherwise not be evident in rare disorders [8]. A number of international registries for patients with GD exist, the largest being the International Collaborative Gaucher Group disease registry (ClinicalTrials.gov Identifier: NCT00358943), initiated by Genzyme in 1991 (now Sanofi), followed by the Gaucher Outcome Survey (GOS) disease registry, initiated in 2010 by Shire (now Takeda) after US Food and Drug Administration approval of velaglucerase alfa, and a drug-specific registry Taliglucerase Alfa Surveillance, for patients receiving treatment with taliglucerase alfa, initiated by Pfizer in 2013 (EUPAS4721 [9]), as well as national registries including the Spanish Gaucher Disease Registry, initiated in 1993 [10], the French Gaucher Disease Registry, initiated in 2009 [11], and the GAUCHERITE registry initiated in 2014 in the United Kingdom [12].…”

Plant-derived single domain COVID-19 antibodies

“…Plant cell suspension cultures are commonly cultivated in simple inexpensive liquid medium compared to mammalian cells and can offer significant advantages, including high safety, low production cost and easy scale-up. The potential of a plant cell suspension system for rapid production at a commercial scale has been demonstrated by the marketing of taliglucerase alfa (Elelyso®) for Gaucher disease that is produced in transgenic carrot cell suspension cultures [ [35] , [36] , [37] ]. Plant rapid production systems can quickly respond to pandemic crisis like COVID-19, as demonstrated during the Ebola outbreak by the manufacture of ZMapp, a cocktail of tobacco-produced monoclonal antibodies that confer protection against the Ebola virus [ 38 ].…”