At the 81st Scientific Sessions of the American Diabetes Association (ADA) annual meeting, researchers from Massachusetts General Hospital (MGH) presented an update on their trials of the Bacillus Calmette-Guerin (BCG) vaccine as a treatment for type 1 diabetes (T1D). The presentation (abs: 1142-P) included an increased understanding of how the age of onset affects a patient’s response to BCG, and additional data to support its ability to alter glucose transport and address the over-methylation of regulatory T-cells (Tregs). Because the lack of a disease-modifying therapeutic is a critical unmet need in T1D, as identified by key opinion leaders (KOLs) interviewed by GlobalData, BCG is well-positioned as a repurposed drug to out-compete more expensive pipeline immunotherapy options to address this unmet need.
BCG is originally a vaccine for tuberculosis (TB) and is used in many countries with a high prevalence of the infectious disease. In the US, the vaccine is not generally recommended for use as there is a low risk of infection, and there is potential interference with the tuberculin skin test reactivity and may cause a false-positive result. BCG is almost 100 years old, but while its primary use has been in tuberculosis, the BCG vaccine has also been investigated for its use in bladder cancer, multiple sclerosis and, most recently, Covid-19.
Data from the Phase I trial were first presented by lead researcher Denise Faustman at ADA in 2018, but were quickly met with controversy. The presented results of the follow-up to the Phase I trial showed lasting drops in HbA1c values that persisted with eight years of follow-up while continuing supplemental information. Many participants at ADA that year, however, misinterpreted that BCG itself could restore normal blood sugar levels, branding BCG as a ‘cure’ for T1D. This misunderstanding and vast excitement over the trial results prompted the ADA and Juvenile Diabetes Research Foundation (JDRF) to release an unprecedented joint statement urging a cautionary approach when interpreting the data, noting the study’s small sample size and the need for further investigation before the results could be touted as promising.
The MGH team presented data from the ongoing five-year Phase II study at ADA last week and demonstrated several new findings. The study found that over a period of three years, BCG can return gene expression in Tregs in T1D patients to a pattern consistent with non-type 1 control subjects. In addition, patients with an onset before 21 years of age had a faster response time and were able to achieve a greater change in HbA1c than adult-onset patients, showing a response at two years that matched the three-year response shown in older subjects. This Phase II study includes 150 patients and is expected to be complete in two years.
To date, 236 patients have been enrolled in the randomised and open-label MGH trials and 143 patients have received at least two doses of BCG, 34 of whom are being followed in open-label, unblinded trials. MGH is awaiting approval from the US Food and Drug Administration (FDA) for a paediatric study of 150 participants planned for this year. MGH also aims to conduct several additional human clinical trials, including trials for those with longstanding T1D.
The only treatment currently available for T1D is the administration of exogenous insulin, and there is no approved treatment that actually addresses the disease’s underlying cause. There are several therapeutics in the late-stage pipeline that aim to be disease-modifying for T1D, such as Provention Bio’s teplizumab and Dompé Farmaceutici’s ladarixin. But like BCG so far, these therapies do not negate the need for exogenous insulin.
While the long-term effects and greater population effects of BCG remain to be seen, one major advantage for the vaccine is its accessibility. As a vaccine that has been prevalent for almost a century, it is likely that pricing will not be a barrier for patients who wish to take BCG. In addition, two doses of BCG, as part of the clinical trials, have been effective in patients with longstanding diabetes, whereas the late-stage pipeline is focusing its trials on the newly diagnosed population. Accessibility and overall patient population are critical factors that make the presented results exciting and distinctive from other therapeutics in development.