Akagera Medicines reported positive first-in-human Phase 1 data for long-acting AKG-100, showing favorable safety, sustained drug exposure, and encouraging early bactericidal activity against tuberculosis, including drug-resistant TB.
Written By: Shaik Yasmeen, PharmD
Reviewed By: Pharmacally Editorial Team
Akagera Medicines has reported positive results from the single-ascending-dose (SAD) portion of its first-in-human Phase 1 trial evaluating AKG-100, an investigational long-acting intravenous therapy for tuberculosis (TB), including multidrug-resistant tuberculosis (MDR-TB). The study found that AKG-100 was well tolerated across all tested dose levels while delivering prolonged drug exposure that could enable dosing at intervals measured in weeks or potentially months instead of daily treatment.
The SAD study enrolled 40 healthy volunteers and 15 patients with pulmonary tuberculosis in a 14-day Early Bactericidal Activity (EBA) cohort. Participants received single intravenous doses of AKG-100 ranging up to 850 mg.
Long-Acting Platform Targets a Major Challenge in Tuberculosis Care
Tuberculosis remains one of the world’s deadliest infectious diseases, with treatment requiring prolonged multidrug regimens that often extend for six months or longer. Adherence to daily therapy remains a major obstacle, particularly for patients with drug-resistant disease, increasing the risk of treatment failure and further antimicrobial resistance.
AKG-100 uses Akagera’s proprietary lipid nanoparticle (LNP) delivery platform to provide sustained systemic drug exposure following a single intravenous administration. Unlike first-line TB drugs such as rifampicin and isoniazid, AKG-100 acts through an independent mechanism and has demonstrated retained activity against multidrug-resistant clinical isolates.
Phase 1 Study Shows Favorable Safety and Sustained Drug Exposure
AKG-100 demonstrated a favorable safety profile across every evaluated dose. No participants discontinued treatment because of adverse events, and most reported events were mild and self-limiting.
Pharmacokinetic analyses showed that drug concentrations remained above the predefined therapeutic target for at least 14 days after a single infusion. Modeling further predicted that therapeutic exposure could persist for approximately 28 days, supporting the potential for substantially less frequent dosing than current standard therapy.
Investigators also reported encouraging early antibacterial activity in an exploratory model-based analysis of the tuberculosis patient cohort. A single dose administered on Day 1 was associated with an estimated 3.7 log10 reduction in bacterial burden by Day 14, representing approximately 99.98% bacterial killing. The analysis also predicted an improvement of roughly 298 hours in time to culture positivity compared with baseline.
Although these findings are exploratory and derived from a single-dose cohort, investigators said they compare favorably with historical early bactericidal activity benchmarks and justify further clinical evaluation.
Investigators Highlight Potential to Simplify Tuberculosis Treatment
Akagera Chief Medical Officer Dr. Sachin Marulkar said the study represents an important milestone toward reducing the lengthy daily treatment burden faced by tuberculosis patients. He noted that the observed pharmacokinetic profile supports the possibility of dosing over months if confirmed in later-stage studies.
TASK Group founder and Chief Scientific Officer Prof. Andreas Diacon said the early data combined favorable tolerability with strong bactericidal activity and suggested that long-acting therapies could substantially reduce pill burden, improve treatment adherence, and help limit the development of resistance.
Akagera’s Chief Scientific Officer Dr. Daryl Drummond added that the study provides the first clinical evidence that the company’s lipid nanoparticle platform can deliver sustained exposure for a tuberculosis therapeutic as intended.
Multiple-Ascending-Dose Study Underway
Based on the positive SAD findings, the multiple-ascending-dose (MAD) portion of the Phase 1 program is now underway. The study will further evaluate the safety, pharmacokinetics, and clinical potential of repeated AKG-100 dosing as Akagera advances development of a long-acting treatment that could simplify therapy for both drug-susceptible and drug-resistant tuberculosis.
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About the Writer
Shaik Yasmeen (LinkedIn) is a Pharm.D graduate with interests in clinical pharmacy, pharmacovigilance, and medical writing. She has gained experience through hospital clinical postings, patient case reviews, case presentations, and literature evaluation. Passionate about evidence-based healthcare, she is committed to creating accurate and engaging medical content while continuously expanding her professional knowledge.