LXE408 / Novartis - LARVOL DELTA

Visceral leishmaniasis: an integrated review of resistance mechanisms, host immunometabolism, and next generation therapeutics. (PubMed, Inflammopharmacology) - "On the therapeutic side, the present article assesses the existing evidence base of combination regimens, host-directed approaches, and new oral pipeline of novel oral candidates, under clinical development by DNDi and partner institutions, such as LXE408, DNDI-6174, liposomal nanoformulations. Further, the article provides a survey of the topography of diagnostic instruments, including strong points and translational shortcomings of parasitological confirmation, molecular and serological. Together, this review highlights the necessity of combined, surveillance-based, and target-specific strategies in order to support and prolong the achieved progress in VL eradication."

Journal • Review • Infectious Disease • AQP1

A First-in-human, Safety, Tolerability, and Pharmacokinetics Study of LXE408 in Healthy Subjects (clinicaltrials.gov) - P1 | N=88 | Completed | Sponsor: Novartis Pharmaceuticals

First-in-human • New P1 trial • Infectious Disease

A Study of Efficacy, Safety, Tolerability of LXE408 in Participants With Chronic Chagas Disease. (clinicaltrials.gov) - P2 | N=130 | Recruiting | Sponsor: Novartis Pharmaceuticals | Trial completion date: Sep 2030 ➔ Jan 2031 | Trial primary completion date: Mar 2027 ➔ Jul 2027

Trial completion date • Trial primary completion date

A Clinical Trial to Investigate Efficacy, Safety and Pharmacokinetics (PK) of Two LXE408 Oral Regimens and Oral Miltefosine as Active Control in Participants Aged ≥ 18 Years Old With Localized Cutaneous Leishmaniasis in the Region of the Americas (AMR). (clinicaltrials.gov) - P2 | N=250 | Not yet recruiting | Sponsor: Drugs for Neglected Diseases | Trial completion date: Jul 2027 ➔ Apr 2028 | Initiation date: Nov 2025 ➔ Jun 2026 | Trial primary completion date: Jul 2027 ➔ Apr 2028

Trial completion date • Trial initiation date • Trial primary completion date • Dermatology • Infectious Disease

A Phase II, Multicentre, Randomized, Two-arm Blinded Study to Assess the Efficacy and Safety of Two LXE408 Regimens for Treatment of Patients With Primary Visceral Leishmaniasis (clinicaltrials.gov) - P2 | N=101 | Completed | Sponsor: Drugs for Neglected Diseases | Active, not recruiting ➔ Completed

Trial completion • Infectious Disease

A Study of Efficacy, Safety, Tolerability of LXE408 in Participants With Chronic Chagas Disease. (clinicaltrials.gov) - P2 | N=130 | Recruiting | Sponsor: Novartis Pharmaceuticals | Trial completion date: Sep 2027 ➔ Sep 2030

Trial completion date

LXE408 for Treatment of Visceral Leishmaniasis in Ethiopia, a Proof of Concept Study (clinicaltrials.gov) - P2 | N=52 | Completed | Sponsor: Drugs for Neglected Diseases | Active, not recruiting ➔ Completed

Trial completion • Infectious Disease

A Phase II, Multicentre, Randomized, Two-arm Blinded Study to Assess the Efficacy and Safety of Two LXE408 Regimens for Treatment of Patients With Primary Visceral Leishmaniasis (clinicaltrials.gov) - P2 | N=101 | Active, not recruiting | Sponsor: Drugs for Neglected Diseases | Trial primary completion date: Jul 2025 ➔ Apr 2025

Trial primary completion date • Infectious Disease

Optimization and prioritization of paediatric drugs for visceral leishmaniasis. (PubMed, Front Pediatr) - "The group prioritized a 20 mg scored, dispersible tablet formulation of miltefosine and an oral solid dosage form of amphotericin B, acknowledging recent developments in allometric dosing for miltefosine and ongoing research for the development of oral amphotericin B. For miltefosine, this prompted an ongoing update of the WHO Prequalification Expression of interest to promote generic manufacturing. A compound with a new mechanism of action, LXE408, which is currently being investigated in Phase II, was included in the PADO watch list, signalling that paediatric investigations should start as soon as enough data are available from adult studies, not to delay access to latest available innovations for children with VL."

Journal • Infectious Disease • Pediatrics

A Phase II, Multicentre, Randomized, Two-arm Blinded Study to Assess the Efficacy and Safety of Two LXE408 Regimens for Treatment of Patients With Primary Visceral Leishmaniasis (clinicaltrials.gov) - P2 | N=101 | Active, not recruiting | Sponsor: Drugs for Neglected Diseases | Recruiting ➔ Active, not recruiting | Trial completion date: Jan 2025 ➔ Dec 2025 | Trial primary completion date: Jan 2025 ➔ Jul 2025

Enrollment closed • Trial completion date • Trial primary completion date • Infectious Disease

LXE408 for Treatment of Visceral Leishmaniasis in Ethiopia, a Proof of Concept Study (clinicaltrials.gov) - P2 | N=52 | Active, not recruiting | Sponsor: Drugs for Neglected Diseases | Recruiting ➔ Active, not recruiting

Enrollment closed • Infectious Disease

A Clinical Trial to Investigate Efficacy, Safety and Pharmacokinetics (PK) of Two LXE408 Oral Regimens and Oral Miltefosine as Active Control in Participants Aged ≥ 18 Years Old With Localized Cutaneous Leishmaniasis in the Region of the Americas (AMR). (clinicaltrials.gov) - P2 | N=250 | Not yet recruiting | Sponsor: Drugs for Neglected Diseases

New P2 trial • Dermatology • Infectious Disease

A Study of Efficacy, Safety, Tolerability of LXE408 in Participants With Chronic Chagas Disease. (clinicaltrials.gov) - P2 | N=130 | Recruiting | Sponsor: Novartis Pharmaceuticals | Not yet recruiting ➔ Recruiting

Enrollment open

Novartis Gets CDSCO Panel Nod To Study Antiparasitic Drug LXE408 (Medical Dialogues) - "Drug major Novartis has got approval from the Subject Expert Committee (SEC) functional under the Central Drug Standard Control Organisation (CDSCO) to conduct the clinical study of the antiparasitic drug LXE408...The firm presented phase 1 clinical study protocol no.: CLXE408A12105 amendment version no. 1 dated 31- January- 2025....After detailed deliberation, the committee recommended the grant of permission to conduct the trial as presented by the firm."

New P1 trial • Infectious Disease

A Study of Efficacy, Safety, Tolerability of LXE408 in Participants With Chronic Chagas Disease. (clinicaltrials.gov) - P2 | N=130 | Not yet recruiting | Sponsor: Novartis Pharmaceuticals | Trial completion date: Jan 2028 ➔ Oct 2027 | Initiation date: Aug 2025 ➔ Apr 2025 | Trial primary completion date: Jul 2027 ➔ Apr 2027

Trial completion date • Trial initiation date • Trial primary completion date

Anti-leishmanial therapies: overcoming current challenges with emerging therapies. (PubMed, Expert Rev Anti Infect Ther) - "All three new treatments (Amphotericin-B, paromomycin and miltefosine) which underwent the clinical trials were repurposed drugs. The current pipeline for antileishmanial drugs is empty, with LXE 408 being the only potential drug reaching phase II clinical trial."

Journal • Review • Infectious Disease

First-in-human, Randomized, Double blind Clinical Trial of LXE408 for Kinetoplastid Diseases (ASTMH 2024) - "LXE408 was safe and well tolerated. Clinical studies are planned or ongoing to assess efficacy in patients with visceral leishmaniasis, cutaneous leishmaniasis, and Chagas disease."

Clinical • P1 data • Constipation • Dermatology • Gastroenterology • Gastrointestinal Disorder • Infectious Disease • Pain • CST3

A Study of Efficacy, Safety, Tolerability of LXE408 in Participants With Chronic Chagas Disease. (clinicaltrials.gov) - P2 | N=130 | Not yet recruiting | Sponsor: Novartis Pharmaceuticals

New P2 trial

The 26 S proteasome in Entamoeba histolytica: divergence of the substrate binding pockets from host proteasomes. (PubMed, BMC Res Notes) - "This was strongly supported by significantly lower sensitivity to MG132 mediated inhibition of amoebic proteasome β5 subunit's chymotryptic activity compared to human proteasomes, also reflected in lower sensitivity of E. histolytica to MG132 for inhibition of proliferation. Selective inhibitors for visceral leishmaniasis, LXE408 and compound 8, docked well to this pocket. This functional and sequence-based analysis predicts differences between amoebic and host proteasomes that can be utilized to develop rationally designed, selective inhibitors against E. histolytica."

Journal • Infectious Disease • Targeted Protein Degradation

LXE408 for Treatment of Visceral Leishmaniasis in Ethiopia, a Proof of Concept Study (clinicaltrials.gov) - P2 | N=52 | Recruiting | Sponsor: Drugs for Neglected Diseases | Not yet recruiting ➔ Recruiting | Trial primary completion date: Sep 2025 ➔ Jun 2025

Enrollment open • Trial primary completion date • Infectious Disease

LXE408 for Treatment of Visceral Leishmaniasis in Ethiopia, a Proof of Concept Study (clinicaltrials.gov) - P2 | N=52 | Not yet recruiting | Sponsor: Drugs for Neglected Diseases | Trial completion date: Jan 2025 ➔ Jul 2025 | Initiation date: Sep 2023 ➔ Jan 2024

Trial completion date • Trial initiation date • Infectious Disease

LXE408 for Treatment of Visceral Leishmaniasis in Ethiopia, a Proof of Concept Study (clinicaltrials.gov) - P2 | N=52 | Not yet recruiting | Sponsor: Drugs for Neglected Diseases

New P2 trial • Infectious Disease

A Phase II, Multicentre, Randomized, Two-arm Blinded Study to Assess the Efficacy and Safety of Two LXE408 Regimens for Treatment of Patients With Primary Visceral Leishmaniasis (clinicaltrials.gov) - P2 | N=105 | Recruiting | Sponsor: Drugs for Neglected Diseases | Not yet recruiting ➔ Recruiting

Enrollment open • Infectious Disease

A Phase II, Multicentre, Randomized, Two-arm Blinded Study to Assess the Efficacy and Safety of Two LXE408 Regimens for Treatment of Patients With Primary Visceral Leishmaniasis (clinicaltrials.gov) - P2 | N=105 | Not yet recruiting | Sponsor: Drugs for Neglected Diseases

New P2 trial • Infectious Disease

Small molecules as kinetoplastid specific proteasome inhibitors for Leishmaniasis: a patent review from 1998 to 2021. (PubMed, Expert Opin Ther Pat) - "LXE408 and GSK3494245 are two KSPIs in different phases of clinical trials. The KSPIs are promising next-generation orally active patient compliant drugs against kinetoplastid diseases, including leishmaniasis. However, the main challenge to discover the KSPIs will be the resistance development and their selectivity against the proteasome of eukaryotic cells."

Journal • Review • Infectious Disease