Delving into the Latest Updates on Rilematovir with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

JNJ-53718678, JNJ-678, JNJ-8678

Target

RSV F protein

Mechanism

Respiratory syncytial virus F protein inhibitors

Therapeutic Areas

Infectious DiseasesRespiratory DiseasesDigestive System Disorders

Active Indication-

Inactive Indication

Acute lower respiratory tract infectionAcute respiratory infectionsAcute upper respiratory infection+ [3]

Originator Organization

Johnson & Johnson

Active Organization-

Inactive Organization

Janssen Research & Development LLCJanssen Sciences Ireland ULCJanssen Sciences Ireland UC

+ [1]

Drug Highest PhaseDiscontinuedPhase 3

First Approval Date-

RegulationBreakthrough Therapy (CN)

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Structure

Molecular FormulaC21H20ClF3N4O3S

InChIKeyGTQTUABHRCWVLL-UHFFFAOYSA-N

CAS Registry1383450-81-4

Respiratory syncytial virus (RSV) is a leading cause of acute respiratory infection amongst all ages, causing a significant global health burden. Preventative and therapeutic options for RSV infection have long been under development, and recently, several widely‐publicised vaccines targeting older adult and maternal populations have become available. Promising monoclonal antibody (mAb) and antiviral (AV) therapies are also progressing in clinical trials, with the prophylactic mAb nirsevimab recently approved for clinical use in infant populations. A systematic review on current progress in this area is lacking. We performed a systematic literature search (PubMed, Embase, Web of Science, ClinicalTrials.gov, EudraCT, ANZCTR—searched Nov 29th, 2023) to identify studies on all RSV‐specific mAbs and AV therapies that has undergone human clinical trials since year 2000. Data extraction focused on outcomes related to the therapeutic efficacy and safety of the intervention on trial, and all studies were graded against the OCEBM Levels of Evidence Table. Results from 59 studies were extracted, covering efficacy and safety data on six mAbs (motavizumab, motavizumab‐YTE, nirsevimab, ALX‐0171, suptavumab, clesrovimab) and 12 AV therapies (ALN‐RSV01, RSV604, presatovir, MDT‐637, lumicitabine, IFN‐α1b, rilematovir, enzaplatovir, AK0529, sisunatovir, PC786, EDP‐938). Of the mAbs reviewed, nirsevimab and clesrovimab hold considerable promise. The timeline for RSV‐specific AV availability is less advanced, although EDP‐938 and AK0529 have reported promising phase 2 efficacy and safety data. Moving forward, passive immunisation and treatment options for RSV infection will play a significant role in reducing the health burden of RSV, complementing recent advancements in vaccine development.

Trial Registration:

PROSPERO registration: CRD42022376633

01 Jul 2024·Paediatric drugs

CROCuS, a Phase II Study Evaluating the Antiviral Activity, Clinical Outcomes, and Safety of Rilematovir in Children Aged ≥ 28 Days and ≤ 3 Years with Acute Respiratory Tract Infection Due to Respiratory Syncytial Virus

Article

Author: Luz, Kleber ; Calvo, Cristina ; Ferrero, Fernando ; Lin, Chien-Yu ; Stevens, Marita ; Baguet, Tristan ; Vijgen, Leen ; Deleu, Sofie ; Nemeth, Agnes ; Gamil, Mohamed ; Toh, Teck-Hock ; Rusch, Sarah ; Sánchez, Beatriz López ; Liese, Johannes ; Chen, Bohang ; Huntjens, Dymphy ; Gijón, Manuel ; Stoeva, Tatyana ; Leipoldt, Illse ; Natalini, Silvina ; Bertzos, Kristi

BACKGROUND:

Respiratory syncytial virus (RSV) causes significant morbidity and mortality in children aged ≤ 5 years and adults aged ≥ 60 years worldwide. Despite this, RSV-specific therapeutic options are limited. Rilematovir is an investigational, orally administered inhibitor of RSV fusion protein-mediated viral entry.

OBJECTIVE:

To establish the antiviral activity, clinical outcomes, safety, and tolerability of rilematovir (low or high dose) in children aged ≥ 28 days and ≤ 3 years with RSV disease.

METHODS:

CROCuS was a multicenter, international, double-blind, placebo-controlled, randomized, adaptive phase II study, wherein children aged ≥ 28 days and ≤ 3 years with confirmed RSV infection who were either hospitalized (Cohort 1) or treated as outpatients (Cohort 2) were randomized (1:1:1) to receive rilematovir (low or high dose) or placebo. Study treatment was administered daily as an oral suspension from days 1 to 7, with dosing based on weight and age groups. The primary objective was to establish antiviral activity of rilematovir by evaluating the area under the plasma concentration-time curve of RSV viral load in nasal secretions from baseline through day 5. Severity and duration of RSV signs and symptoms and the safety and tolerability of rilematovir were also assessed through day 28 (± 3).

RESULTS:

In total, 246 patients were randomized, treated, and included in the safety analysis population (Cohort 1: 147; Cohort 2: 99). Of these, 231 were included in the intent-to-treat-infected analysis population (Cohort 1: 138; Cohort 2: 93). In both cohorts, demographics were generally similar across treatment groups. In both cohorts combined, the difference (95% confidence interval) in the mean area under the plasma concentration-time curve of RSV RNA viral load through day 5 was - 1.25 (- 2.672, 0.164) and - 1.23 (- 2.679, 0.227) log₁₀ copies∙days/mL for the rilematovir low-dose group and the rilematovir high-dose group, respectively, when compared with placebo. The estimated Kaplan-Meier median (95% confidence interval) time to resolution of key RSV symptoms in the rilematovir low-dose, rilematovir high-dose, and placebo groups of Cohort 1 was 6.01 (4.24, 7.25), 5.82 (4.03, 8.18), and 7.05 (5.34, 8.97) days, respectively; in Cohort 2, estimates were 6.45 (4.81, 9.70), 6.26 (5.41, 7.84), and 5.85 (3.90, 8.27) days, respectively. A similar incidence of adverse events was reported in patients treated with rilematovir and placebo in Cohort 1 (rilematovir: 61.9%; placebo: 58.0%) and Cohort 2 (rilematovir: 50.8%; placebo: 47.1%), with most reported as grade 1 or 2 and none leading to study discontinuation. The study was terminated prematurely, as the sponsor made a non-safety-related strategic decision to discontinue rilematovir development prior to full recruitment of Cohort 2.

CONCLUSIONS:

Data from the combined cohort suggest that rilematovir has a small but favorable antiviral effect of indeterminate clinical relevance compared with placebo, as well as a favorable safety profile. Safe and effective therapeutic options for RSV in infants and young children remain an unmet need.

CLINICAL TRIAL REGISTRATION:

EudraCT Number: 2016-003642-93; ClinicalTrials.gov Identifier: NCT03656510. First posted date: 4 September, 2018.

01 Oct 2023·Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases

A pilot phase 2a, randomized, double-blind, placebo-controlled study to explore the antiviral activity, clinical outcomes, safety, and tolerability of rilematovir at two dose levels in non-hospitalized adults with respiratory syncytial virus infection

Article

Author: Sinha, Rekha ; Guzman Romero, Ana Karla ; Luz, Kleber ; Napora, Piotr ; Draghi, Jorge ; Aggarwal, Naresh ; Rusch, Sarah ; Stevens, Marita ; Scott, Jane ; Vijgen, Leen ; Huntjens, Dymphy ; Gupta, Anil ; Pullman, John ; Nilsson, Anna C ; Petrova, Galina ; Bertzos, Kristi ; Ianus, Juliana

OBJECTIVES:

To assess the antiviral effect, clinical outcomes, and safety of the respiratory syncytial virus (RSV) fusion inhibitor rilematovir in non-hospitalized RSV-infected adults.

METHODS:

This phase 2a, double-blind, multicentre study randomly assigned RSV-positive adult outpatients ≤5 days from symptom onset 1:1:1 to receive rilematovir 500 mg, 80 mg, or placebo once-daily for 7 days. Antiviral effect was assessed by RSV RNA viral load (VL), measured by quantitative RT-PCR, and Kaplan-Meier (KM) estimates of time to undetectable VL. Clinical course was assessed by KM estimates of median time to resolution of key RSV symptoms assessed through patient-reported outcomes.

RESULTS:

RSV-positive patients (n = 72) were randomly assigned; 66 had confirmed RSV infection and received rilematovir 500 mg (n = 23), 80 mg (n = 21) or placebo (n = 22). Differences versus placebo in mean RSV RNA VL area under the curve (90% CI) through days 3, 5 and 8, respectively, were 0.09 (-0.837; 1.011), -0.10 (-2.171; 1.963), and -1.03 (-4.746; 2.682) log₁₀ copies.day/mL for rilematovir 500 mg, and 1.25 (0.291; 2.204), 2.53 (0.430; 4.634), and 3.85 (0.097; 7.599) log₁₀ copies.day/mL for rilematovir 80 mg. KM estimates of median (90% CI) time-to-first confirmed undetectable VL were 5.9 (3.85; 6.90), 8.0 (6.86; 12.80) and 7.0 (6.62; 10.88) days and 5.7 (2.93; 7.01), 8.1 (6.74; 12.80) and 7.9 (6.62; 11.74) days in patients with symptom onset ≤3 days, for rilematovir 500 mg, 80 mg, and placebo, respectively. KM estimates of median (90% CI) time to resolution of key RSV symptoms were 7.1 (5.03; 11.43), 7.6 (5.93; 8.32), and 9.6 (5.95; 14.00) days for rilematovir 500 mg, 80 mg, and placebo, respectively; and in patients with symptom onset ≤3 days, median 8.0, 7.6, and 11.8 days, respectively.

DISCUSSION:

Rilematovir use, initiated early, suggests a potential clinical benefit in RSV-infected adults, with data supporting development of RSV therapeutic options.

TRIAL REGISTRATION:

This study is registered with clinicaltrials.gov (NCT03379675).

100 Deals associated with Rilematovir

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External Link

KEGG	Wiki	ATC	Drug Bank
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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Acute lower respiratory tract infection	Phase 3	US	Janssen Research & Development LLC	06 Sep 2021
Acute lower respiratory tract infection	Phase 3	CN	Janssen Research & Development LLC	06 Sep 2021
Acute lower respiratory tract infection	Phase 3	JP	Janssen Research & Development LLC	06 Sep 2021
Acute lower respiratory tract infection	Phase 3	AR	Janssen Research & Development LLC	06 Sep 2021
Acute lower respiratory tract infection	Phase 3	BE	Janssen Research & Development LLC	06 Sep 2021
Acute lower respiratory tract infection	Phase 3	BR	Janssen Research & Development LLC	06 Sep 2021
Acute lower respiratory tract infection	Phase 3	BG	Janssen Research & Development LLC	06 Sep 2021
Acute lower respiratory tract infection	Phase 3	CZ	Janssen Research & Development LLC	06 Sep 2021
Acute lower respiratory tract infection	Phase 3	EE	Janssen Research & Development LLC	06 Sep 2021
Acute lower respiratory tract infection	Phase 3	DE	Janssen Research & Development LLC	06 Sep 2021

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT03656510 (CTgov)	Phase 2	Acute lower respiratory tract infection \| Respiratory Syncytial Virus Infections	246	placebo+JNJ-53718678 (Cohorts 1 and 2: Placebo)	kxrhlhzjhr(octwketssw) = fmciuymrlk pppkszsadm (aybwfpqonw, hxtjwwdidy - ayibbnijbg) View more	-	21 Sep 2023
				JNJ-53718678 (Cohorts 1 and 2: JNJ-53718678 Low Dose)	kxrhlhzjhr(octwketssw) = jazwnrwccz pppkszsadm (aybwfpqonw, lwrhtbakcy - qlguhoxyec) View more
NCT03379675 (Pubmed)	Phase 2	Respiratory Syncytial Virus Infections	72	Rilematovir 500 mg	pcvuesdodq(khyccioqmo) = ocxoilwbsv lmsgsmnyof (kohbbmtooj, -0.837 to 1.011) View more	-	06 Jul 2023
				Rilematovir 80 mg	pcvuesdodq(khyccioqmo) = jfelizyocn lmsgsmnyof (kohbbmtooj, -2.171 to 1.963) View more
NCT04978337 (PRIMROSE, CTgov)	Phase 2	Pneumonia due to respiratory syncytial virus	5	placebo+rilematovir (Placebo)	xhwwrpgxue(wvxqcxmazj) = wwnvzdcwkb jathdbiauz (ropvpofbrb, fxoqmmvjli - mozcwlagrg) View more	-	21 Apr 2023
				Rilematovir (Rilematovir 250 mg Bid)	ejzghczjfe(ghawuezjiv) = amfjeqshon oeanqajmyw (zjsxpqvfbq, xxgxjwlmls - cdxtksskub) View more
NCT04056611 (FREESIA, CTgov)	Phase 2	Respiratory Syncytial Virus Infections	3	rilematovir	rfdgsgbaug(ixpvchkirv) = vuisrlrgrh inaolejwuf (ecskdxobcs, ccyyodgfqu - ipqbwyfxhw) View more	-	14 Apr 2023
NCT04583280 (DAISY, CTgov)	Phase 3	Acute lower respiratory tract infection \| Respiratory Syncytial Virus Infections	28	Placebo (Placebo)	hgxkrjyxnp(sdhebtqthd) = owuuozxulj dmfggintjt (cmymkzarpf, xjargxllng - rpjsdbxynl) View more	-	10 Apr 2023
				Rilematovir X mg/kg (Rilematovir)	hgxkrjyxnp(sdhebtqthd) = vtjphzjiwc dmfggintjt (cmymkzarpf, axfifikwyv - iyleppikue) View more
NCT03379675 (CTgov)	Phase 2	Respiratory Syncytial Virus Infections	72	JNJ-53718678 500 mg (Treatment A: JNJ-53718678 500 mg)	yvgtffecas(fulysqazsn) = gkcudymwxg pxadcjqhcb (wbrwiwybou, kfbylgfrwh - hwhnscohwf) View more	-	28 Jun 2022
				Placebo+JNJ-53718678 80 mg (Treatment B: JNJ-53718678 80 mg + Placebo)	yvgtffecas(fulysqazsn) = hpiplgnxlg pxadcjqhcb (wbrwiwybou, fvxlslgvji - zanmhnawua) View more
NCT04068792 (CTgov)	Phase 2	Acute upper respiratory infection \| Acute lower respiratory tract infection \| Respiratory Syncytial Virus Infections	22	placebo+JNJ-53718678 (Placebo)	mmijucvotk(jpomgjrjcz) = nztjxyvxtm sfmxlsejdb (bfejejlerv, xmzarqlqqa - yhxwvcncqc) View more	-	08 Jun 2022
				JNJ-53718678 (JNJ-53718678)	mmijucvotk(jpomgjrjcz) = jhjusyxzfu sfmxlsejdb (bfejejlerv, tvafvnoosf - ynnugqrojx) View more
EUCTR2014-005041-41-GB \| NCT02387606 (Pubmed \| Am J Trop Med Hyg \| J Infect Dis) Manual	Phase 2	Respiratory Syncytial Virus Infections	69	JNJ-53718678	xhizooxjyc(hnibepmlto) = bnhsvcolpr emhwcbddss (ucyhkiwbru ) View more	Positive	24 Jul 2018
				Placebo	xhizooxjyc(hnibepmlto) = otrqrkbpgi emhwcbddss (ucyhkiwbru ) View more