Safety and Tolerability of Triumeq in Amyotrophic Lateral Sclerosis: The Lighthouse Trial
30 Pages Posted: 8 Mar 2019More...
Background: Neuroinflammation and human endogenous retroviruses (HERV-K) are thought to have a role in the pathophysiology of amyotrophic lateral sclerosis (ALS). Therapy directed against endogenous retroviruses has demonstrated positive effects during in-vitro and biomarker studies. Consequently, the present study was undertaken to assess the safety and tolerability of long-term Triumeq (abacavir, lamivudine and dolutegravir) exposure in patients with ALS and to assess efficacy against biomarkers of disease progression.
Methods: Patients were observed during a 10-week lead-in period before receiving Triumeq treatment for 24 weeks at four specialist ALS centres. The primary outcomes were safety and tolerability. Secondary outcomes included HERV-K expression levels, urinary p75ECD levels, neurophysiological parameters and clinical outcomes. The ENCALS prediction model was applied to provide an estimate of the cohort survival. The trial was registered on www.clinicaltrials.gov (NCT02868580).
Findings: 40 patients with ALS received Triumeq and 35 (88%) completed treatment. There were no drug-related serious adverse events; one patient was withdrawn from the study due to a drug-associated increase in liver enzymes. A favourable response on HERV-K expression levels was observed, accompanied by a potential slowing in ALSFRS-R progression rate of 21.8% (95% CI -4.8 %- 48.6%) and the amount of urinary p75ECD measured. One patient died five months after stopping treatment, while five were expected to have died during the treatment period (interquartile range 2-8).
Interpretation: Long-term Triumeq exposure was safe and well tolerated. There was suggestive evidence for a biological response in pharmacodynamic and clinical biomarkers. A larger international phase III trial will be deployed to assess the effect of Triumeq on overall survival and disease progression.
Funding: Funding was provided by the FightMND Foundation; MND Research Institute of Australia; MND Association, United Kingdom. ViiV Healthcare provided the Triumeq.
Declaration of Interest: The authors have no conflict of interest with respect to the research or data presented in this study. No funder was involved in the study design or interpretation or reporting of the results.
Ethical Approval: The relevant ethics committees at each site approved the protocol. The study was conducted in accordance with Good Clinical Practice (GCP) and the Declaration of Helsinki (2000). The trial was registered on clinicaltrials.gov (NCT02868580).
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