WO2024252355A1 - Schémas posologiques pédiatriques comprenant un inhibiteur de fusion pour le traitement du vrs - Google Patents

Schémas posologiques pédiatriques comprenant un inhibiteur de fusion pour le traitement du vrs Download PDF

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WO2024252355A1
WO2024252355A1 PCT/IB2024/055600 IB2024055600W WO2024252355A1 WO 2024252355 A1 WO2024252355 A1 WO 2024252355A1 IB 2024055600 W IB2024055600 W IB 2024055600W WO 2024252355 A1 WO2024252355 A1 WO 2024252355A1
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sisunatovir
dose
subject
month
old
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Arthur James BERGMAN
Ryan Michael FRANKE
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Pfizer Inc
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/4164—1,3-Diazoles
    • A61K31/4184—1,3-Diazoles condensed with carbocyclic rings, e.g. benzimidazoles
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • A61P31/14—Antivirals for RNA viruses

Definitions

  • Respiratory Syncytial Virus is a negative-sense, single-stranded RNA virus of the Pneumoviridae family. RSV is readily transmitted by secretions from an infected person via surfaces or hand-to-hand transfer. Following successful inoculation, the incubation period is between four and six days during which time the virus spreads from the nasopharynx to the lower respiratory tract by fusion of infected with uninfected cells and by sloughing of the necrotic epithelium. In infants, coupled with increased mucus secretion and oedema, this can lead to mucus plugging causing hyper-inflation and collapse of distal lung tissue indicative of bronchiolitis.
  • RSV Respiratory Syncytial Virus
  • RSV pneumonia inflammatory infiltration of the airways consists of mononuclear cells and is more generalized, with involvement of the bronchioles, bronchi and alveoli. The duration and degree of viral shedding has been found to correlate with the clinical signs and severity of disease.
  • RSV is the leading cause of serious respiratory tract infections in infants and young children throughout the world. The highest morbidity and mortality occur in those born prematurely and for those with chronic lung or heart disease, although many infants hospitalized for RSV infection are otherwise healthy. Severe RSV infection in infancy can lead to several years of recurrent wheezing and is linked to the later development of asthma.
  • RSV is also a major cause of morbidity and mortality in the elderly and in immunocompromised children and adults as well as those with chronic obstructive pulmonary disease (COPD) and congestive heart failure (CHF).
  • COPD chronic obstructive pulmonary disease
  • CHF congestive heart failure
  • Small molecules have also been proposed as inhibitors of RSV. These include benzimidazoles and benzodiazepines.
  • benzimidazole inhibitors of RSV are disclosed in WO 02/062290 and WO 03/053344 (Squibb Bristol Myers Co); WO 2010/103306 (Astrazeneca UK Ltd); and WO 2013/068769, WO 2016/055780, WO 2019/016566 and WO 2019/122928 (ReViral Limited).
  • RSV604 a benzodiazepine compound having sub-micromolar anti-RSV activity, is described in Antimicrobial Agents and Chemotherapy, Sept. 2007, 3346-3353 (Chapman et al).
  • Benzodiazepine inhibitors of RSV are also disclosed in publications including WO 2004/026843 and WO 2005/089770 (Arrow Therapeutics Limited); WO 2016/166546 and WO 2018/033714 (Durham University); WO 2017/015449, WO 2018/129287 and WO 2018/226801 (Enanta Pharmaceuticals, Inc.); and WO 2021/079121 , WO 2021/084280, WO 2021/032992, WO 2022/008911 and WO 2022/008912 (ReViral Limited).
  • Sisunatovir and preparation thereof is described in international publication WO 2016/055780.
  • Clinical studies in adults have investigated the pharmacokinetics of sisunatovir (DeVincenzo et aL, Antimicrobial Agents and Chemotherapy Feb. 2020 Vol. 64 issue 2).
  • the contents of each of the foregoing documents are incorporated herein by reference in their entirety.
  • sisunatovir hydrochloride salt (HCI) adult dosing is expected to be 200 mg twice daily (DeVincenzo et al). Based on allometric scaling, pediatric doses with comparable exposure to adults was predicted to be approximately 2 mg/kg for pediatric patients aged 1 month to ⁇ 6 months and 2.5 mg/kg for pediatric patients aged 6 months to 36 months. However, it was unexpectedly found these doses resulted in unacceptably low exposures compared to adults and that the dose to pediatric patients aged 1 to 60 months should be much higher to achieve comparable exposure to adult patients.
  • the present invention provides, in part, dosing regimens for administering sisunatovir, or a pharmaceutically acceptable salt thereof, to a subject as a single agent, and in combination therapies, for treating RSV infection in pediatric populations.
  • a method for treating RSV infection comprising administering to a 1- to 60-month-old subject in need thereof a dose of from about 4.0 mg/kg to about 8.0 mg/kg of sisunatovir HCI, wherein the dose is administered twice per day (BID or Q12h).
  • Embodiment 1 (E1 ) is identical to the embodiment provided above.
  • FIG. 1 shows the results of a Phase 2 Open-Label Study in Infants with Respiratory Syncytial Virus Lower Respiratory Tract Infection, followed by a Double-blind, Placebo Controlled Part, to Evaluate the Safety, Tolerability, Pharmacokinetics and Antiviral Effect of RV521 (sisunatovir).
  • E2 A method of embodiment E1 , wherein the dose is from about 4.0 mg/kg to about 7 mg/kg of sisunatovir HCI.
  • E3 A method of embodiment E1 , wherein the dose is from about 4.0 mg/kg to about 6.5 mg/kg of sisunatovir HCI.
  • E4 A method of embodiment E1 , wherein the dose is from about 4.2 mg/kg to about 6.5 mg/kg of sisunatovir HCI.
  • E5 A method of embodiment E1 , wherein the dose is from about 4.5 mg/kg to about 6.0 mg/kg of sisunatovir HCI.
  • E6 A method of embodiment E1 , wherein the subject is a 1 - to 6-month-old and wherein the dose is from about 4.0 mg/kg to about 7.0 mg/kg of sisunatovir HCI.
  • E7 A method of embodiment E1 , wherein the subject is a 1 - to 6-month-old and wherein the dose is from about 4.0 mg/kg to about 6.0 mg/kg of sisunatovir HCI.
  • E8 A method of embodiment E1 , wherein the subject is a 1 - to 6-month-old and wherein the dose is from about 4.0 mg/kg to about 5.5 mg/kg of sisunatovir HCI.
  • E9 A method of embodiment E1 , wherein the subject is a 1 - to 6-month-old and wherein the dose is from about 4.0 mg/kg to about 5.0 mg/kg of sisunatovir HCI.
  • E10 A method of embodiment E1 , wherein the subject is a 1 - to 6-month-old and wherein the dose is from about 4.2 mg/kg to about 4.8 mg/kg of sisunatovir HCI.
  • E11 A method of embodiment E1 , wherein the subject is a 1 - to 6-month-old and wherein the dose is from about 4.5 mg/kg of sisunatovir HCI.
  • E12 A method of embodiment E1 , wherein the subject is a 6- to 12-month-old and wherein the dose is from about 4.0 mg/kg to about 7.0 mg/kg of sisunatovir HCI.
  • E13 A method of embodiment E1 , wherein the subject is a 6- to 12-month-old and wherein the dose is from about 4.0 mg/kg to about 6.0 mg/kg of sisunatovir HCI.
  • E14 A method of embodiment E1 , wherein the subject is a 6- to 12-month-old and wherein the dose is from about 4.5 mg/kg to about 6.0 mg/kg of sisunatovir HCI.
  • E15 A method of embodiment E1 , wherein the subject is a 6- to 12-month-old and wherein the dose is from about 5.0 mg/kg to about 6.0 mg/kg of sisunatovir HCI.
  • E16 A method of embodiment E1 , wherein the subject is a 6- to 12-month-old and wherein the dose is from about 5.2 mg/kg to about 5.8 mg/kg of sisunatovir HCI.
  • E17 A method of embodiment E1 , wherein the subject is a 6- to 12-month-old and wherein the dose is from about 5.5 mg/kg of sisunatovir HCL
  • E18 A method of embodiment E1 , wherein the subject is a 12- to 60-month-old and wherein the dose is from about 4.0 mg/kg to about 7.0 mg/kg of sisunatovir HCL
  • E19 A method of embodiment E1 , wherein the subject is a 12- to 60-month-old and wherein the dose is from about 4.5 mg/kg to about 7 mg/kg of sisunatovir HCL
  • E20 A method of embodiment E1 , wherein the subject is a 12- to 60-month-old and wherein the dose is from about 5.0 mg/kg to about 7.0 mg/kg of sisunatovir HCL
  • E21 A method of embodiment E1 , wherein the subject is a 12- to 60-month-old and wherein the dose is from about 5.5 mg/kg to about 6.5 mg/kg of sisunatovir HCL
  • E22 A method of embodiment E1 , wherein the subject is a 12- to 60-month-old and wherein the dose is from about 5.7 mg/kg to about 6.3 mg/kg of sisunatovir HCL
  • E23 A method of embodiment E1 , wherein the subject is a 12- to 60-month-old and wherein the dose is from about 6.0 mg/kg of sisunatovir HCL
  • E24 A method for treating RSV infection comprising administering to a 1- to 60-month-old subject in need thereof a total daily dose of from about 8.0 mg/kg to about 16.0 mg/kg of sisunatovir HCL
  • E25 A method of embodiment E24 wherein the total daily dose is from about 8.0 mg/kg to about 13 mg/kg.
  • E26 A method of embodiment E24 wherein the subject is a 1- to 6-month-old and the total daily dose is from about 8 mg/kg to about 10 mg/kg.
  • E27 A method of embodiment E24 wherein the subject is a 6- to 12-month-old and the total daily dose is from about 10 mg/kg to about 12 mg/kg.
  • E28 A method of embodiment E24 wherein the subject is a 12- to 60-month-old and the total daily dose is from about 11 mg/kg to about 13 mg/kg.
  • E29 A method according to any of embodiments E1 to E28 and E30 to E40 wherein sisunatovir HCI is administered orally.
  • E30 A method according to embodiment E1 wherein the dose is about 5 mg/kg to about 6.0 of sisunatovir HCI.
  • E31 A method for treating RSV infection according to any of the embodiments E1 to E30 and E32 to E40 wherein the dosage of sisunatovir HCI is replaced by an equivalent dosage of sisunatovir free base.
  • E32 A method for treating RSV infection comprising administering to a 6- to 36-month-old subject in need thereof a dose of from about 4.0 mg/kg to about 5.5 mg/kg of sisunatovir HCI, or a pharmaceutically acceptable salt thereof, wherein the dose is administered twice per day (BID).
  • E33 A method of embodiment E32, wherein the dose is from about 4.0 mg/kg to about 5.0 mg/kg.
  • E34 A method of embodiment E32, wherein the dose is from about 4.25 mg/kg to about 5.0 mg/kg.
  • E35 A method of embodiment E32, wherein the dose is from about 4.25 mg/kg to about 4.75 mg/kg.
  • E36 A method of embodiment E32, wherein the dose is from about 4.3 mg/kg to about 4.6 mg/kg.
  • E37 A method of embodiment E32, wherein the dose is from about 4.4 mg/kg to about 4.6 mg/kg.
  • E38 A method of embodiment E32, wherein the dose is about 4.5 mg/kg.
  • the term “about” when used to modify a numerically defined parameter means that the parameter may vary by as much as 20% below or above the stated numerical value for that parameter.
  • a dose of about 5 mg/kg means 5 mg/kg ⁇ 20%, i.e., it may vary between 4 mg/kg and 6 mg/kg.
  • the term “combination”, unless otherwise indicated, means a fixed-dose combination or a combination of agents that is administered intermittently, concurrently, or sequentially, according to the same or different route of administration and according to the same or different dosage schedules.
  • treating As used herein, the terms “treating”, “treat” or “treatment”, unless otherwise indicated, embraces both preventative, i.e., prophylactic, and palliative treatment, i.e., relieve, alleviate, or slow the progression of the patient’s RSV infection or any tissue damage associated with the RSV infection.
  • the phrase “effective dose” refers to the amount of sisunatovir that elicits the biological or medicinal response in the 1 - to 60-month-old subject, which may include one or more of the following:
  • inhibiting the disease for example, inhibiting the RSV infection in a 1 - to 60- month-old subject that is experiencing or displaying the pathology or symptomatology of the RSV infection (i.e., arresting (or slowing) further development of the pathology or symptomatology or both); and
  • sisunatovir to treat RSV infection is administered in an amount effective to treat a condition as described herein.
  • Sisunatovir may be administered as compound per se, or alternatively, as a pharmaceutically acceptable salt.
  • sisunatovir may be administered as a hydrochloride salt (HCI).
  • HCI hydrochloride salt
  • suitable salts see Handbook of Pharmaceutical Salts: Properties, Selection, and Use by Stahl and Wermuth (Wiley-VCH, 2002). Methods for making pharmaceutically acceptable salts of compounds described herein are known to one of skill in the art.
  • Sisunatovir may administered by any suitable route in the form of a pharmaceutical composition adapted to such a route, and in a dose effective for the treatment intended.
  • Sisunatovir may be administered orally. Oral administration may involve swallowing, so that sisunatovir enters the gastrointestinal tract, or buccal or sublingual administration may be employed by which the compound enters the bloodstream directly from the mouth.
  • the daily dose of sisunatovir or a pharmaceutically acceptable salt thereof is administered orally twice a day.
  • Sisunatovir may be present in a pharmaceutical composition which includes at least one pharmaceutically acceptable excipient.
  • “Pharmaceutically acceptable excipient” refers to a component that may be included in the compositions described herein, is physiologically suitable for pharmaceutical use, and causes no significant adverse effects nor therapeutic effects to a subject.
  • excipient is used herein to describe any ingredient other than the compound(s) of the invention. The choice of excipient will to a large extent depend on factors such as the mode of administration, the effect of the excipient on solubility and stability, and the nature of the dosage form.
  • the amount of sisunatovir, or a pharmaceutically acceptable salt, in the pharmaceutical compositions can be any amounts disclosed herein.
  • the formulation will preferably be adapted to the particular mode of administration.
  • These compounds may be formulated with pharmaceutically acceptable excipients as known in the art and administered in a wide variety of dosage forms as known in the art.
  • Dosage unit forms or pharmaceutical compositions suitable for oral administration include, but are not limited to tablets, capsules, such as gelatin capsules, pills, powders, granules, aqueous and nonaqueous oral solutions and suspensions, packaged in containers adapted for subdivision into individual doses.
  • Example 1 Phase 2 Sisunatovir Clinical Trial In Pediatric Population
  • Sisunatovir was investigated in a Phase 2 Open-Label Study in Infants with Respiratory Syncytial Virus Lower Respiratory Tract Infection, followed by a Double-blind, Placebo Controlled Part, to Evaluate the Safety, Tolerability, Pharmacokinetics and Antiviral Effect of RV521 (sisunatovir).
  • the overall study design is detailed in FIG. 1 .
  • the study contains two parts, Part A and Part B: To evaluate the safety and tolerability of single (Part A) and multiple (Part B) oral doses of RV521 in infants hospitalized with RSV lower respiratory tract infection (LRTI).
  • Part A single (Part A) and multiple (Part B) oral doses of RV521 in infants hospitalized with RSV lower respiratory tract infection (LRTI).
  • Part B single (Part A) and multiple (Part B) oral doses of RV521 in infants hospitalized with RSV lower respiratory tract infection (LRTI).
  • LRTI lower respiratory tract infection
  • PK population pharmacokinetic
  • FDA Food and Drug Administration
  • EMEA European Medicines Evaluation Agency
  • FDA Food and Drug Administration
  • EMEA European Medicines Evaluation Agency
  • the model was verified using standard checks, such as Visual Predictive Check plots, bootstrap analysis, and goodness-of-fit plots (EMA, 2007), which compared the predicted concentration values to actual observed concentrations as well as showed the residual differences between predicted and actual concentrations as an assessment of model validity.
  • the model was informed with the available demographic covariates to allow the incorporation of a nonlinear dose effect, formulation, and/or food effect, and available body weight and age data to support extrapolation to infants.
  • the simulated exposure was restricted by the lower bound for efficacy, using the EC90 for RSV inhibition, applied to the unbound concentration after the first dose (Dose 1 ) at the end of the dosing interval of 12 hours (minimum concentration [Cmin]). This equated to a total sisunatovir concentration of 7.3 ng/mL (converted from unbound).
  • Initial target was Cmin of ⁇ 21 ng/mL in Part A.
  • exposure (Cmin, Cmax, and area under the curve from time zero to tau [the dosing interval] [AUCtau]) targets were comparable to 200 mg Q12h in adults. 200 mg Q12h in adults was found to be efficacious in C5241002 (viral challenge study).
  • the Cmax and AUCtau for the last dose (Dose 10) of the BID dosing regimen in adult subjects dosed at 350 mg of sisunatovir were used as a guideline and are presented in a separate report (Syneos Health, 2018). Therefore, the upper limit for dose levels was selected such that the peak plasma exposure levels did not exceed the group mean values observed in Clinical Study C5241002 [formerly referenced as REVC002]) (Cmax of 294 ng/mL) and total exposure (AUCtau 2500 ngxh/mL).
  • the resulting proposed starting doses for Part A from Phoenix NLME population PK model, Cohort 2 was 2 mg/kg for infants >1 month to ⁇ 6 months of age and for Part A, Cohort 1, was 2.5 mg/kg for infants >6 months to ⁇ 36 months of age for actual doses and dose adjustments.
  • the first group of 3 subjects enrolled into Cohort 1 received a single dose of 2.5 mg/kg sisunatovir suspended in pharmacopoeial- grade water administered by oral syringe.
  • the initial dose of 2.5 mg/kg sisunatovir suspended in pharmacopoeial-grade water only 2 out of 3 subjects had 1 post-Dose sample collected, only
  • Dose adjustments for sisunatovir in Cohort 1 were made as follows: and then 2.0 mg/kg. At a dose of 2.0 mg/kg suspended in formula milk for oral administration, 6 out 7 subjects had quantifiable concentrations of sisunatovir through the 6-to-8-hour post-Dose timepoint, with 2 out of 7 subjects remaining quantifiable for sisunatovir until at least 12 hours post-Dose. Approval of protocol version 4.0 and country-specific amendments permitted the use of either formula milk or breast milk as a suspending diluent for dose administration via oral syringe (pharmacopeial-grade water was still recommended for dose administration via nasogastric tube). All 7 subjects in Cohort 1 were dosed with 2.0 mg/kg via oral syringe with sisunatovir suspended in formula milk.
  • Subjects in Cohort 2 (age: >1 month to ⁇ 6 months) were dosed with 2.0 mg/kg sisunatovir suspended in either formula milk or pharmacopeial-grade water depending on the route of administration.
  • Three of the subjects were dosed via oral syringe using formula milk as the suspending diluent, and 3 were dosed via nasogastric tube using pharmacopeial-grade water as the suspending diluent.
  • Part B Part B
  • the Phoenix NLME Population PK model was updated with data from Part A and used to predict doses for Part B.
  • the Phoenix NLME popPK model was built with C5241001 , C5241002 adult data and Part A (single dose) pediatric data from C5241003.
  • the first group of 3 subjects enrolled into Cohort 3 received 10 doses of 2.5 mg/kg sisunatovir suspended in 0.9% weight per volume (w/v) sodium chloride (saline) administered by oral syringe.
  • Dose adjustments for sisunatovir in Cohort 3 was made as follows: 3.5 mg/kg, because the Phoenix NLME Population PK prediction for 2.5 mg/kg too low.
  • Two subjects were dosed at 3.5 mg/kg via oral syringe with sisunatovir suspended in saline.
  • One subject was dosed at 3.5 mg/kg via nasogastric tube using pharmacopoeial-grade water as the suspending diluent for doses 1 -7 and via oral syringe with sisunatovir suspended in saline for doses 8-10.
  • One subject was dosed at 3.5 mg/kg via oral syringe with sisunatovir suspended in saline for doses 1 -3 and with sisunatovir suspended in formula milk for doses 4-10. Exposures from 3.5 mg/kg were too low.
  • Dose adjustments for sisunatovir in Cohort 3 was as follows: 5.0 mg/kg, because exposures from 3.5 mg/kg were too low. One subject was dosed at 5 mg/kg sisunatovir suspended in formula milk via oral syringe for doses 1 and 10, and via nasogastric tube for doses 2-9. One subject was dosed at 5 mg/kg via oral syringe with sisunatovir suspended in formula milk via oral syringe.
  • Table 1 below compares key simulation data for pediatric patients aged 1 to 6 months, 6 to 12 months, and 12 to 60 months from a NONMEM population pharmacokinetic model to data from sisunatovir studies in adults (DeVincenzo et aL).
  • the table included values obtained for steady-state trough concentration (CtroughSS), steady-state maximum concentration (CmaxSS), and area under the curve from time zero to time tau (the dosing interval) (AUCtauSS) predicted to achieve a comparable exposure to adults receiving 200 mg twice daily.
  • At least 4.5 mg/kg is the predicted appropriate dosage for 1 - to 6-month-old patients BID (twice daily), at least 5.5 mg/kg is the predicted appropriate dosage for 6- to 12-month-old patients BID (twice daily), and at least 6 mg/kg is predicted appropriate dosage for 12- to 60-month-old patients BID (twice daily). Doses could increase up to the limit of impurity specification (8 mg/kg BID [twice daily]).
  • NONMEM nonlinear mixed-effect modeling

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Abstract

L'invention concerne des schémas posologiques pour le traitement d'une infection par le VRS comprenant l'administration à un sujet pédiatrique en ayant besoin d'une dose quotidienne de sisunatovir en tant qu'agent unique ou en combinaison avec d'autres thérapies du VRS.
PCT/IB2024/055600 2023-06-08 2024-06-07 Schémas posologiques pédiatriques comprenant un inhibiteur de fusion pour le traitement du vrs Ceased WO2024252355A1 (fr)

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Citations (19)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2002062290A2 (fr) 2000-12-20 2002-08-15 Bristol-Myers Squibb Company Agents antiviraux constitues de 2-methylbenzimidazole substitue heterocyclique
WO2003053344A2 (fr) 2001-12-10 2003-07-03 Bristol-Myers Squibb Company 2-methyl-benzimidazole substitues en tant qu'agents antiviraux du virus respiratoire syncytial
WO2004026843A1 (fr) 2002-09-20 2004-04-01 Arrow Therapeutics Limited Derives de benzodiazepine et compositions pharmaceutiques les renfermant
WO2005089770A1 (fr) 2004-03-19 2005-09-29 Arrow Therapeutics Limited Benzodiazepines pour traiter ou empecher une infection due au virus syncytial respiratoire
WO2010103306A1 (fr) 2009-03-10 2010-09-16 Astrazeneca Uk Limited Dérivés de benzimidazole et leur utilisation comme agents antiviraux
WO2013068769A1 (fr) 2011-11-10 2013-05-16 Re:Viral Ltd Composés pharmaceutiques
WO2016055780A1 (fr) 2014-10-07 2016-04-14 Re:Viral Ltd Spiro-indolines pour le traitement et la prophylaxie de l'infection par le virus respiratoire syncytial (vrs)
WO2016166546A1 (fr) 2015-04-16 2016-10-20 The University Of Durham Composé antimicrobien
WO2017015449A1 (fr) 2015-07-22 2017-01-26 Enanta Pharmaceuticals, Inc. Dérivés benzodiazépine utilisés comme inhibiteurs du virus respiratoire syncytial (rsv)
WO2018033714A1 (fr) 2016-08-15 2018-02-22 The University Of Durham Composé antimicrobien
WO2018129287A1 (fr) 2017-01-06 2018-07-12 Enanta Pharmaceuticals, Inc. Dérivés d'hétéroaryldiazépine utilisés comme inhibiteurs du vrs
WO2018226801A1 (fr) 2017-06-07 2018-12-13 Enanta Pharmaceuticals, Inc. Dérivés d'aryldiazépine utilisés en tant qu'inhibiteurs du vrs
WO2019016566A1 (fr) 2017-07-20 2019-01-24 ReViral Limited Composés pharmaceutiques
WO2019122928A1 (fr) 2017-12-22 2019-06-27 ReViral Limited Composés pharmaceutiques
WO2021032992A1 (fr) 2019-08-20 2021-02-25 ReViral Limited Composés pharmaceutiques
WO2021079121A1 (fr) 2019-10-22 2021-04-29 ReViral Limited Dérivés de benzodiazépine pour le traitement d'une infection par le virus respiratoire syncytial (rsv)
WO2021084280A1 (fr) 2019-11-01 2021-05-06 ReViral Limited Composés pharmaceutiques
WO2022008912A1 (fr) 2020-07-07 2022-01-13 ReViral Limited Dérivés de benzodiazépine utiles dans le traitement d'une infection par le virus respiratoire syncytial
WO2022008911A1 (fr) 2020-07-07 2022-01-13 ReViral Limited Dérivés de benzodiazépine utiles pour le traitement d'une infection par le virus respiratoire syncytial

Patent Citations (19)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2002062290A2 (fr) 2000-12-20 2002-08-15 Bristol-Myers Squibb Company Agents antiviraux constitues de 2-methylbenzimidazole substitue heterocyclique
WO2003053344A2 (fr) 2001-12-10 2003-07-03 Bristol-Myers Squibb Company 2-methyl-benzimidazole substitues en tant qu'agents antiviraux du virus respiratoire syncytial
WO2004026843A1 (fr) 2002-09-20 2004-04-01 Arrow Therapeutics Limited Derives de benzodiazepine et compositions pharmaceutiques les renfermant
WO2005089770A1 (fr) 2004-03-19 2005-09-29 Arrow Therapeutics Limited Benzodiazepines pour traiter ou empecher une infection due au virus syncytial respiratoire
WO2010103306A1 (fr) 2009-03-10 2010-09-16 Astrazeneca Uk Limited Dérivés de benzimidazole et leur utilisation comme agents antiviraux
WO2013068769A1 (fr) 2011-11-10 2013-05-16 Re:Viral Ltd Composés pharmaceutiques
WO2016055780A1 (fr) 2014-10-07 2016-04-14 Re:Viral Ltd Spiro-indolines pour le traitement et la prophylaxie de l'infection par le virus respiratoire syncytial (vrs)
WO2016166546A1 (fr) 2015-04-16 2016-10-20 The University Of Durham Composé antimicrobien
WO2017015449A1 (fr) 2015-07-22 2017-01-26 Enanta Pharmaceuticals, Inc. Dérivés benzodiazépine utilisés comme inhibiteurs du virus respiratoire syncytial (rsv)
WO2018033714A1 (fr) 2016-08-15 2018-02-22 The University Of Durham Composé antimicrobien
WO2018129287A1 (fr) 2017-01-06 2018-07-12 Enanta Pharmaceuticals, Inc. Dérivés d'hétéroaryldiazépine utilisés comme inhibiteurs du vrs
WO2018226801A1 (fr) 2017-06-07 2018-12-13 Enanta Pharmaceuticals, Inc. Dérivés d'aryldiazépine utilisés en tant qu'inhibiteurs du vrs
WO2019016566A1 (fr) 2017-07-20 2019-01-24 ReViral Limited Composés pharmaceutiques
WO2019122928A1 (fr) 2017-12-22 2019-06-27 ReViral Limited Composés pharmaceutiques
WO2021032992A1 (fr) 2019-08-20 2021-02-25 ReViral Limited Composés pharmaceutiques
WO2021079121A1 (fr) 2019-10-22 2021-04-29 ReViral Limited Dérivés de benzodiazépine pour le traitement d'une infection par le virus respiratoire syncytial (rsv)
WO2021084280A1 (fr) 2019-11-01 2021-05-06 ReViral Limited Composés pharmaceutiques
WO2022008912A1 (fr) 2020-07-07 2022-01-13 ReViral Limited Dérivés de benzodiazépine utiles dans le traitement d'une infection par le virus respiratoire syncytial
WO2022008911A1 (fr) 2020-07-07 2022-01-13 ReViral Limited Dérivés de benzodiazépine utiles pour le traitement d'une infection par le virus respiratoire syncytial

Non-Patent Citations (4)

* Cited by examiner, † Cited by third party
Title
CHAPMAN ET AL., ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, September 2007 (2007-09-01), pages 3346 - 3353
DEVINCENZO ET AL., ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, vol. 64, February 2020 (2020-02-01)
DEVINCENZO JOHN ET AL: "A Randomized, Placebo-Controlled, Respiratory Syncytial Virus Human Challenge Study of the Antiviral Efficacy, Safety, and Pharmacokinetics of RV521, an Inhibitor of the RSV-F Protein", ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, vol. 64, no. 2, 27 January 2020 (2020-01-27), US, XP093189544, ISSN: 0066-4804, Retrieved from the Internet <URL:https://journals.asm.org/doi/pdf/10.1128/AAC.01884-19> DOI: 10.1128/AAC.01884-19 *
STAHLWERMUTH: "Handbook of Pharmaceutical Salts: Properties, Selection, and Use", 2002, WILEY-VCH

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Tab Levsin Drops
AGONIST Pediatric:< 3 years: not established; 3-12: initiate at 62.5 mg orally twice daily; for patients weighing> 40 kg, increase to 125 mg orally twice daily after 4 weeks;> 12 years: same as adult Tracleer Tab: 62.5, 125 mg film-coat; Tab for oral suspension: 32 mg
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