Baseline characteristics of 32 patients with Gaucher disease who were treated with imiglucerase: South African data from the International Collaborative Gaucher Group (ICGG) Gaucher Registry.

BACKGROUND: Gaucher disease (GD) is a rare inherited autosomal recessive metabolic disorder with a prevalence in the general population of ~1 per 100 000. To optimise the recognition, diagnosis and management of patients with GD in South Africa (SA), it is important to have an understanding of local patterns of presentation of the disease. OBJECTIVES: To describe the baseline pretreatment characteristics of the SA cohort of patients enrolled into the International Collaborative Gaucher Group (ICGG) Gaucher Registry whowere treated with imiglucerase (Cerezyme; Sanofi Genzyme). METHODS: The ICGG Gaucher Registry is an observational, longitudinal, international database that tracks the clinical, demographic, genetic, biochemical and therapeutic characteristics of patients with GD globally, irrespective of disease severity, treatment status or treatment choice. The study population included all SA patients reported in the ICGG Gaucher Registry as of 1 May 2020. RESULTS: The registry included 49 SA GD patients, of whom 32 received imiglucerase as first primary GD therapy. All the patients had GD type 1, 59.4% were female, and mean and median ages at diagnosis were 14.7 and 9.8 years, respectively. The most common genotype was N370S/N370S (37.5%). At treatment initiation, 30.0% of patients had been splenectomised. Among patients for whom data were available, anaemia was present in one-third of non-splenectomised patients and 12.5% of those with splenectomy, and moderate or severe thrombocytopenia was reported in two-thirds of non-splenectomised patients. Bone pain was present in 30.8% and 57.1% of non- splenectomised and splenectomised patients, respectively. No bone crises were reported, and data relating to other bone complications were available for only ≤3 patients. CONCLUSIONS: Haematological findings and bone pain in this group are similar to those in the global ICGG Gaucher Registry cohort. Lack of baseline data for other bone complications limits interpretation in that regard. Clinicians who treat patients with GD are encouraged to submit accurate, complete and up-to-date information so that comprehensive data for the subset of SA GD patients can be maintained to improve recognition and diagnosis, and guide appropriate and effective use of treatment for SA patients.

A double-blind, randomised, placebo-controlled, dose-finding trial of the novel tuberculosis vaccine AERAS-402, an adenovirus-vectored fusion protein, in healthy, BCG-vaccinated infants.

BACKGROUND: Several novel tuberculosis vaccines are currently in clinical trials, including AERAS-402, an adenovector encoding a fusion protein of Mycobacterium tuberculosis antigens 85A, 85B, and TB10.4. A multicentred trial of AERAS-402 safety and immunogenicity in healthy infants was conducted in three countries in sub-Saharan Africa, using an adaptive design. METHODS: In a double-blind, randomised, placebo-controlled, dose-finding trial, we enrolled BCG-vaccinated, HIV-uninfected infants aged 16-26 weeks. Infants in the safety/dose-finding phase received two doses of AERAS-402 across three dose levels, or placebo, intramuscularly on days 0 and 28. Infants in the expanded safety phase received three doses of the highest dose level, with the 3rd dose at day 280. Follow up for safety and immunogenicity was for up to two years. RESULTS: We enrolled 206 infants (52 placebo and 154 AERAS-402 recipients) into the dose-finding phase and 281 (141 placebo and 140 AERAS-402 recipients) into the expanded safety phase. Safety data were acceptable across all dose levels. No vaccine-related deaths were recorded. A single serious adverse event of tachypnoea was deemed related to study vaccine. Antibodies directed largely against Ag85A and Ag85B were detected. Low magnitude CD4+ and CD8+ polyfunctional T cell responses were observed at all dose levels. The addition of a third dose of AERAS-402 at the highest dose level did not increase frequency or magnitude of antibody or CD8+ T cell responses. CONCLUSIONS: AERAS-402 has an acceptable safety profile in infants and was well tolerated at all dose levels. Response rate was lower than previously seen in BCG vaccinated adults, and frequency and magnitude of antigen-specific T cells were not increased by a third dose of vaccine.