RARE DISEASE
Lassa fever
Lassa fever
Lassa fever
Synonyms: LF, Lassa hemorrhagic fever
Synonyms: LF, Lassa hemorrhagic fever
Synonyms: LF, Lassa hemorrhagic fever
Drug discovery
1
drug
With orphan designation
Overview
Lassa fever is an acute viral hemorrhagic illness caused by the Lassa virus, endemic in West Africa. Transmission occurs through contact with rodent excreta or contaminated materials, with human-to-human spread in healthcare settings lacking infection controls. Symptoms progress from nonspecific flu-like symptoms to multi-organ failure in severe cases (15% CFR in hospitalized patients). Early diagnosis remains challenging due to symptom overlap with malaria and typhoid. Ribavirin (IV/oral) is used as off-label treatment despite incomplete efficacy data, and supportive care is critical for survival [1][3][13].
Categories: rare infectious diseases
Research Papers
707 drug discovery papers related to Lassa fever, with 3 first-in-class and 5 next-in-class early-stage therapies forecasted to outperform the average preclinical success rate. Recent publications:
707 drug discovery papers related to Lassa fever, with 3 first-in-class and 5 next-in-class early-stage therapies forecasted to outperform the average preclinical success rate. Recent publications:
2026-06-27 | Evaluating vectors for the design of a spillover-disrupting Lassa virus transmissible vaccine.
Lassa fever is a viral zoonotic disease that sickens tens of thousands of people each year when it spills over from its rodent reservoir throughout West Africa. Despite the burden this persistent spillover places on public health, stopping it has proven to be an intractable challenge despite decades of investment and effort. A revolutionary solution is the development of a transmissible vaccine that can spread through the rodent population resulting in immune coverage sufficient to eliminate Lassa virus transmission. Here, we evaluate the feasibility of a transmissible vaccine constructed from native cytomegaloviruses (CMVs) previously isolated from the natural reservoir of Lassa virus, Mastomys natalensis. Using a combination of field sampling, large-scale CMV genome characterization, and mathematical models parameterized using Bayesian methods, we quantified transmission rates and interactions among viruses in northern Sierra Leone. The results demonstrate that two of the three previously isolated CMVs co-infect freely and have R0 values consistent with autonomous elimination of Lassa virus from its rodent reservoir. These results set the stage for the development of a CMV vectored transmissible vaccine that could stop the spillover of Lassa virus throughout West Africa.
2026-06-26 | Missed Opportunities for Timely Diagnosis and Effective Therapeutic Management of Prolonged Fever: A Case Study of Confirmed Lassa Fever in N'Zérékoré, Guinea, 2022.
Lassa fever is a potentially fatal viral hemorrhagic disease caused by a ribonucleic acid (RNA) virus of the Arenaviridae family, endemic in West Africa. It is highly virulent and contagious in several countries, with a nonspecific clinical presentation that poses a major public health challenge. An in-depth investigative survey was conducted in N'Zérékoré to identify the transmission chain of a confirmed case of Lassa fever. This study reports a confirmed case of Lassa fever diagnosed 13 days after the onset of persistent fever. The disease was suspected at the regional hospital of N'Zérékoré following the worsening of the initial clinical picture, characterized by the onset of hemorrhagic manifestations and failure of antibiotic therapy. Confirmation of Lassa virus infection by reverse transcriptase-polymerase chain reaction (RT-PCR) on a blood sample was obtained a day prior to the patient's death. The patient did not receive ribavirin treatment and remained on the same antibiotic regimen (ceftriaxone) from the onset of fever, combined with dexamethasone, omeprazole, and a unit of blood transfusion. The therapeutic pathway of this confirmed Lassa fever case in N'Zérékoré highlights the need for improved management of viral hemorrhagic fevers and consideration of differential diagnoses when broad-spectrum antibiotic therapy fails.
2026-06-10 | Adjuvanted inactivated rabies virus-vectored Lassa virus vaccine in healthy adults: a phase 1 trial.
Lassa fever causes substantial morbidity and mortality in West Africa, and no licensed vaccine is available. We evaluated LASSARAB, an inactivated rabies virus-vectored Lassa virus (Josiah strain) glycoprotein complex vaccine. We conducted a randomized, controlled, dose-escalation phase 1 trial. Participants (total n = 54) received two intramuscular doses of LASSARAB containing 700 (n = 15), 1,400 (n = 15) or 2,800 (n = 14) relative units of antigen formulated with the TLR-4 agonist 3D-6-acyl PHAD-SE adjuvant, or licensed rabies vaccine control (n = 10), administered 28 days apart. This protocol-defined interim analysis reports the primary safety evaluation and secondary immunogenicity assessments through day 61. There were no prespecified hypotheses or formal power calculations. All primary safety end points demonstrated an acceptable safety profile. After dose 1, local solicited adverse events occurred in 86.7-100.0% of LASSARAB groups and 80% of controls; systemic events in 33.3-71.4% and 60.0% of controls. After dose 2, local solicited adverse events occurred in 66.7-86.7% of LASSARAB groups and 55.6% of controls; systemic events in 53.3-71.4% of LASSARAB groups and 55.6% of controls. Events were predominantly mild and self-limited. Unsolicited adverse events occurred in 28.6-60.0% of LASSARAB groups and 20.0% of controls. No serious adverse event, immune-mediated condition or sensorineural hearing loss occurred. Safety laboratory abnormalities occurred in 13.3-66.7% of LASSARAB groups and 30.0% of controls (14 mild, 6 moderate and none severe). After two doses, Lassa virus GPC IgG ELISA seroconversion (≥fourfold rise) was achieved in 100.0% (44 of 44) of LASSARAB recipients and 0.0% (0 of 10) of controls. Rabies glycoprotein IgG ELISA seroconversion (≥fourfold rise) and neutralizing antibody by rapid fluorescent focus inhibition test (RFFIT) seroprotection (≥0.5 IU ml-1) were also 100% across all groups, including controls. LASSARAB + 3D-6-acyl phosphorylated hexaacyl disaccharide (PHAD)-SE demonstrated a favorable safety profile and immunogenicity against Lassa and rabies viruses. The per-protocol final study report will include safety and durability through day 394. ClinicalTrials.gov identifier NCT06546709 .
2026-06-27 | Evaluating vectors for the design of a spillover-disrupting Lassa virus transmissible vaccine.
Lassa fever is a viral zoonotic disease that sickens tens of thousands of people each year when it spills over from its rodent reservoir throughout West Africa. Despite the burden this persistent spillover places on public health, stopping it has proven to be an intractable challenge despite decades of investment and effort. A revolutionary solution is the development of a transmissible vaccine that can spread through the rodent population resulting in immune coverage sufficient to eliminate Lassa virus transmission. Here, we evaluate the feasibility of a transmissible vaccine constructed from native cytomegaloviruses (CMVs) previously isolated from the natural reservoir of Lassa virus, Mastomys natalensis. Using a combination of field sampling, large-scale CMV genome characterization, and mathematical models parameterized using Bayesian methods, we quantified transmission rates and interactions among viruses in northern Sierra Leone. The results demonstrate that two of the three previously isolated CMVs co-infect freely and have R0 values consistent with autonomous elimination of Lassa virus from its rodent reservoir. These results set the stage for the development of a CMV vectored transmissible vaccine that could stop the spillover of Lassa virus throughout West Africa.
2026-06-26 | Missed Opportunities for Timely Diagnosis and Effective Therapeutic Management of Prolonged Fever: A Case Study of Confirmed Lassa Fever in N'Zérékoré, Guinea, 2022.
Lassa fever is a potentially fatal viral hemorrhagic disease caused by a ribonucleic acid (RNA) virus of the Arenaviridae family, endemic in West Africa. It is highly virulent and contagious in several countries, with a nonspecific clinical presentation that poses a major public health challenge. An in-depth investigative survey was conducted in N'Zérékoré to identify the transmission chain of a confirmed case of Lassa fever. This study reports a confirmed case of Lassa fever diagnosed 13 days after the onset of persistent fever. The disease was suspected at the regional hospital of N'Zérékoré following the worsening of the initial clinical picture, characterized by the onset of hemorrhagic manifestations and failure of antibiotic therapy. Confirmation of Lassa virus infection by reverse transcriptase-polymerase chain reaction (RT-PCR) on a blood sample was obtained a day prior to the patient's death. The patient did not receive ribavirin treatment and remained on the same antibiotic regimen (ceftriaxone) from the onset of fever, combined with dexamethasone, omeprazole, and a unit of blood transfusion. The therapeutic pathway of this confirmed Lassa fever case in N'Zérékoré highlights the need for improved management of viral hemorrhagic fevers and consideration of differential diagnoses when broad-spectrum antibiotic therapy fails.
2026-06-10 | Adjuvanted inactivated rabies virus-vectored Lassa virus vaccine in healthy adults: a phase 1 trial.
Lassa fever causes substantial morbidity and mortality in West Africa, and no licensed vaccine is available. We evaluated LASSARAB, an inactivated rabies virus-vectored Lassa virus (Josiah strain) glycoprotein complex vaccine. We conducted a randomized, controlled, dose-escalation phase 1 trial. Participants (total n = 54) received two intramuscular doses of LASSARAB containing 700 (n = 15), 1,400 (n = 15) or 2,800 (n = 14) relative units of antigen formulated with the TLR-4 agonist 3D-6-acyl PHAD-SE adjuvant, or licensed rabies vaccine control (n = 10), administered 28 days apart. This protocol-defined interim analysis reports the primary safety evaluation and secondary immunogenicity assessments through day 61. There were no prespecified hypotheses or formal power calculations. All primary safety end points demonstrated an acceptable safety profile. After dose 1, local solicited adverse events occurred in 86.7-100.0% of LASSARAB groups and 80% of controls; systemic events in 33.3-71.4% and 60.0% of controls. After dose 2, local solicited adverse events occurred in 66.7-86.7% of LASSARAB groups and 55.6% of controls; systemic events in 53.3-71.4% of LASSARAB groups and 55.6% of controls. Events were predominantly mild and self-limited. Unsolicited adverse events occurred in 28.6-60.0% of LASSARAB groups and 20.0% of controls. No serious adverse event, immune-mediated condition or sensorineural hearing loss occurred. Safety laboratory abnormalities occurred in 13.3-66.7% of LASSARAB groups and 30.0% of controls (14 mild, 6 moderate and none severe). After two doses, Lassa virus GPC IgG ELISA seroconversion (≥fourfold rise) was achieved in 100.0% (44 of 44) of LASSARAB recipients and 0.0% (0 of 10) of controls. Rabies glycoprotein IgG ELISA seroconversion (≥fourfold rise) and neutralizing antibody by rapid fluorescent focus inhibition test (RFFIT) seroprotection (≥0.5 IU ml-1) were also 100% across all groups, including controls. LASSARAB + 3D-6-acyl phosphorylated hexaacyl disaccharide (PHAD)-SE demonstrated a favorable safety profile and immunogenicity against Lassa and rabies viruses. The per-protocol final study report will include safety and durability through day 394. ClinicalTrials.gov identifier NCT06546709 .
Access all drug discovery articles and probability of success in trials forecasts:
Access all drug discovery articles and probability of success in trials forecasts:
Drug Discovery Landscape
1 orphan drug designation for Lassa fever.
1 orphan drug designation for Lassa fever.
Drug | Therapy type | Regulator | Orphan designation | Approval | Sponsor |
|---|---|---|---|---|---|
Ribavirin | small molecules | EMA | 2018-03-21 | — | Pharmadev Healthcare Ltd |
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