Last update 21 Jun 2024

Acyclovir

Last update 21 Jun 2024

Overview

R&D Status

Clinical Result

Translational Medicine

Overview

Basic Info

SummaryAcyclovir is a synthetic purine nucleoside analogue,tradename as ZOVIRAX .Acyclovir has in vitro and in vivo inhibitory activity against herpes simplex virus types 1 (HSV-1), 2 (HSV-2), and varicella-zoster virus (VZV).The inhibitory activity of acyclovir is highly selective due to its affinity for the enzyme thymidine kinase (TK) encoded by HSV and VZV. This viral enzyme converts acyclovir into acyclovir monophosphate, a nucleotide analogue. The monophosphate is further converted into diphosphate by cellular guanylate kinase and into triphosphate by a number of cellular enzymes. In vitro, acyclovir triphosphate stops replication of herpes viral DNA. ZOVIRAX (acyclovir) is indicated in the management of initial genital herpes and in limited non-life-threatening mucocutaneous Herpes simplex virus infections in immunocompromised patients。Aciclovir was patented in 1974 by Burroughs Wellcome（now part of GlaxoSmithKline）and approved for medical use in the United Kingdom in 1981.

Drug Type

Small molecule drug

Synonyms

Aciclovir, Aciclovir (JP17/INN), Acycloguanosine

+ [35]

Target

DNA-directed DNA polymerase

Mechanism

DNA-directed DNA polymerase inhibitors

Therapeutic Areas

Infectious DiseasesNervous System DiseasesEye Diseases+ [4]

Active Indication

Keratitis, HerpeticHerpes LabialisEncephalitis, Herpes Simplex+ [4]

Inactive Indication

ChickenpoxHIV Infections

Originator Organization

Burroughs Wellcome

Active Organization

Pfizer Australia Pty Ltd.Bausch Health US LLCBurroughs Wellcome

+ [4]

Inactive Organization

Mylan Pharmaceuticals, Inc.Glaxo Wellcome SA

GSK Plc

+ [1]

Drug Highest PhaseApproved

First Approval Date

GB (01 Jan 1981),

Herpes Simplex

RegulationOrphan Drug (US), Priority Review (CN)

Structure

Molecular FormulaC8H11N5O3

InChIKeyMKUXAQIIEYXACX-UHFFFAOYSA-N

CAS Registry59277-89-3

135

Clinical Trials associated with Acyclovir

CTRI/2024/02/063057 / Not yet recruitingPhase 4

A comparative study of efficacy and safety ofintralesional acyclovir 70mg/ml vs 100mg/ml in common warts including palmoplantar and periungual warts - nil

Start Date02 Mar 2024

Sponsor / Collaborator-

NCT06217406 / Not yet recruitingNot Applicable

Preemptive Treatment With Acyclovir in Intubated and Mechanically Ventilated Patients With Herpes Simplex Virus Oropharyngeal Reactivation and One or Less Organ Failure

This research aims to assess the interest of preemptive treatment with Acyclovir in mechanically ventilated patients with reactivation of Herpes simplex (HSV) in the throat and failure of one organ or less. HSV reactivation is common in patients hospitalized in an intensive care unit (ICU) on invasive mechanical ventilation. It begins at the oropharyngeal level (incidence up to 20-50%), then progresses downward with contamination of the distal airways (reported incidence of 20-65%). HSV reactivation is associated with high mortality. The investigators aim to disable that, in mechanically ventilated patients with HSV reactivation in the throat and failure of one organ or less, preemptive treatment with Acyclovir may reduce mortality.
To answer the question posed in the research, it is planned to include 246 people hospitalized in intensive care on invasive mechanical ventilation, presenting with HSV reactivation of the throat and one organ failure or less.

Start Date01 Mar 2024

Sponsor / Collaborator

Assistance Publique des Hôpitaux de Paris SA

NCT06134492 / RecruitingPhase 3IIT

Effect of Acyclovir Therapy on the Outcome of Mechanically Ventilated Patients With Lower Respiratory Tract Infection and Detection of Herpes Simplex Virus in Bronchoalveolar Lavage

Almost 90 out of 100 people carry herpes simplex viruses (HSV). Once a person has been infected with the herpes viruses, he or she can't get rid of them for the rest of her/his life. For the most part, the viruses are in a dormant state. Only when the immune system is weakened, for example in the case of a serious illness or stress, are the viruses reactivated. They then mainly cause cold sores, which are harmless for healthy people and usually heal without therapy. However, especially in people with a weakened immune system, HSV can also cause serious infections, such as meningitis. In almost every second mechanically ventilated patient in intensive care who has pneumonia, HSV can be detected in the respiratory tract. This is caused by reactivation of the viruses as a result of the severe underlying disease and stress during intensive care therapy. Whether treatment of the herpes viruses (e.g. with acyclovir) is necessary in this situation and helps the patients to cure has not been clarified, especially as acyclovir can also cause side effects such as a deterioration in kidney function. Currently, the physicians decide to treat the herpes viruses in about half of the patients. Several studies have shown that patients for whom the physician decided to treat the viruses survived more often. However, all of these studies looked at the course of the disease only retrospectively and thus are subject to many biases (including physician selection of who receives treatment, missing data). A definitive conclusion as to whether herpesvirus therapy can be recommended cannot be drawn without doubt from these studies. Therefore, the investigators would like to investigate in a randomized controlled trial, i.e. patients are randomly assigned to the experimental (therapy of herpesviruses) or control group (no therapy of herpesviruses), the effect of therapy with acyclovir on survival in mechanically ventilated intensive care patients with lower respiratory tract infection (pneumonia) in whom a large amount of HSV was found in the respiratory tract. The goal of the study is to provide clarity on whether therapy will help patients recover.

Start Date20 Feb 2024

Sponsor / Collaborator

Jena University Hospital

100 Clinical Results associated with Acyclovir

100 Translational Medicine associated with Acyclovir

100 Patents (Medical) associated with Acyclovir

9,593

Literatures (Medical) associated with Acyclovir

01 Feb 2024·The Science of the total environment

Ozonation products of purine derivatives, the basic structures of antiviral micropollutants

Article

Author: Schmidt, Torsten C ; Rockel, Sarah P ; Merkus, Valentina I ; Leupold, Michael S

Purine and its nucleobases adenine and guanine are the basic structures of a large group of antiviral agents such as acyclovir and penciclovir. Hence, their ozonation is of interest with regard to wastewater treatment due to the formation of products that could affect the aquatic environment. In this study, the transformation products of the mentioned substances are investigated under different defined reaction conditions in order to gain insight into the ozonation characteristics of this compound class. Results show that examining related molecules significantly improves product screening by compiling known products and analogues leading to comprehensive candidate lists, for the purines with a total number of >120 candidates (including possible duplicates for several purines) of which 49 were detected for the derivatives studied. One product, cyanuric acid, which was previously postulated for adenine, was tentatively confirmed and quantified for the first time for the reaction of purine and adenine with ozone. In addition, two prioritisation approaches are presented to identify the major products that are either formed under specific reaction conditions or are potentially relevant for structurally related pollutants. First, principal component analysis allowed the prioritisation of the products formed according to reaction conditions. In the analysis of guanine and the two antivirals, this approach showed that at neutral and basic pH the 2-imino-5-oxoimidazoline products dominated while at acidic pH either analogues of 5-amino-2,4-imidazolidinedione or 2,4-diamino-1,3-oxazol-5-(2H)-one were abundant. A second approach prioritising common products in the ozonation of all three basic structures revealed the formation of two products that had not been reported before: C₄H₈O₃ and C₃H₂N₂O₃, presumably oxalylurea. Both molecules or their analogues may also be formed from related micropollutants. Overall, examining basic structures and exemplary micropollutants in combination was shown to be a worthwhile approach to gain knowledge on the ozonation of a whole range of compounds.

01 Feb 2024·Advances in neonatal care : official journal of the National Association of Neonatal Nurses

The Evaluation and Treatment of an Infant Exposed to Nongenital HSV-2

Article

Author: Staggs, Jenna

Background::

Pregnant persons with a primary genital herpes simplex virus (HSV) infection can transfer HSV to the fetus or infant through the placenta or birth canal, which can cause significant infant morbidity or mortality. Primary nongenital infections with HSV-1 or HSV-2 in pregnant persons and the risk of infant infection are not well documented, leaving the clinician to make non-evidence-based decisions on evaluation and treatment in such presentations.

Clinical Findings::

A term newborn was delivered vaginally by a pregnant person with a nongenital HSV-2 infection. The pregnant person's rash first appeared around 32 weeks' gestation, started on their lower back, and terminated on the outer left hip. The rash improved but was still present at time of delivery, and this rash was their first known HSV outbreak.

Primary Diagnosis::

Prenatal exposure to HSV-2.

Interventions::

Diagnostics included the pregnant person's rash surface culture, immunoglobulin G and immunoglobulin M for HSV-1 and -2; infant surface, cerebral spinal fluid (CSF), and serum HSV-1 and HSV-2 polymerase chain reactions (PCRs), infant CSF studies, blood culture, liver function tests, and treatment with intravenous acyclovir.

Outcomes::

This infant remained clinically well during hospitalization and was discharged home at 5 days of life when CSF, surface, and serum PCRs resulted negative.

Practice Recommendations::

Risk for infant HSV infection versus parent/infant separation and exposure to invasive procedures and medications should be considered when pregnant persons present with primary versus recurrent nongenital HSV infections. Research is needed for the evaluation and treatment of infants born to pregnant persons with primary nongenital HSV infections in pregnancy.

01 Feb 2024·Biotechnology and applied biochemistry

Purification and characterization of thioredoxin reductase enzyme from commercial Spirulina platensis tablets by affinity chromatography and investigation of the effects of some chemicals and drugs on enzyme activity

Article

Author: Dagsuyu, Eda ; Yanardag, Refiye

Abstract:

Thioredoxin reductase (TrxR, enzyme code [E.C.] 1.6.4.5) is a widely distributed flavoenzyme that catalyzes nicotinamide adenine dinucleotide phosphate (NADPH)‐dependent reduction of thioredoxin and many other physiologically important substrates. Spirulina platensis is a blue–green algae that is often used as a dietary supplement. S. platensis is rich in protein, lipid, polysaccharide, pigment, carotenoid, enzyme, vitamins and many other chemicals and exhibits a variety of pharmacological functions. In the present study, a simple and efficient method to purify TrxR from S. platensis tablets is reported. The extractions were carried out using two different methods: heat denaturation and 2′,5′‐adenosine diphosphate Sepharose 4B affinity chromatography. The enzyme was purified by 415.04‐fold over the crude extract, with a 19% yield, and specific activity of 0.7640 U/mg protein. Optimum pH, temperature and ionic strength of the enzyme activity, as well as the Michaelis constant (Km) and maximum velocity of enzyme (Vmax) values for NADPH and 5,5′‐dithiobis(2‐nitrobenzoic acid) were determined. Tested metal ions, vitamins, and drugs showed inhibition effects, except Se4+ ion, cefazolin sodium, teicoplanin, and tobramycin that increased the enzyme activity in vitro. Ag+, Cu2+, Mg2+, Ni2+, Pb2+, Zn2+, Al3+, Cr3+, Fe3+, and V4+ ions; vitamin B3, vitamin B6, vitamin C, and vitamin U and aciclovir, azithromycin, benzyladenine, ceftriaxone sodium, clarithromycin, diclofenac, gibberellic acid, glurenorm, indole‐3‐butyric acid, ketorolac, metformin, mupirocin, mupirocin calcium, paracetamol, and tenofovir had inhibitory effects on TrxR. Ag+ exhibited stronger inhibition than 1‐chloro‐2,4‐dinitrobenzene (a positive control).

News (Medical) associated with Acyclovir

07 Apr 2024

·www.globenewswire.com

Candel Therapeutics Announces Positive Interim Data from Randomized Phase 2 Clinical Trial of CAN-2409 in Non-Metastatic Pancreatic Cancer

Updated positive interim data showed notable improvements in estimated median overall survival of 28.8 months after experimental treatment with CAN-2409 versus only 12.5 months in control group in borderline resectable pancreatic ductal adenorcarcinoma (PDAC) At 24 months, survival rate was 71.4% in CAN-2409 treated patients versus only 16.7% in the control group after chemoradiation. At 36 months, estimated survival was 47.6% in the CAN-2409 group versus 16.7% in the control group No new safety signals were observed, providing further support that multiple injections of CAN-2409 were generally well tolerated, with no dose-limiting toxicities and no cases of pancreatitis Previous analysis of resected tumors showed dense aggregates of immune cells, including CD8+, cytotoxic tumor infiltrating lymphocytes, and dendritic cells, in PDAC tissue after CAN-2409 administration, confirming activation of a robust antitumoral immune response April 04, 2024 -- Candel Therapeutics, Inc. (Candel or the Company) (Nasdaq: CADL), a clinical stage biopharmaceutical company focused on developing multimodal biological immunotherapies to help patients fight cancer, today announced updated interim survival data from the ongoing randomized phase 2 clinical trial of CAN-2409 plus valacyclovir (prodrug), together with standard of care (SoC) chemoradiation, followed by resection for borderline resectable pancreatic ductal adenocarcinoma (PDAC). Survival data were updated with eight months of further follow-up since the first analysis presented at the 2023 Society for Immunotherapy (SITC) Annual Meeting. Based on the data presented at SITC, the U.S. Food and Drug Administration (FDA) granted Fast Track Designation to the Company for CAN-2409 in combination with valacyclovir for the treatment of patients with PDAC in December 2023. “Given frequent recurrence and short survival with SoC chemotherapy for non-metastatic PDAC, effective new treatment options are urgently needed,” said Garrett Nichols, MD, MS, Chief Medical Officer of Candel. “We are very encouraged by the improved survival associated with CAN-2409, which has been shown to be durable after prolonged follow-up based on the updated data shown in this randomized clinical trial. CAN-2409 was generally well tolerated without significant additional local or systemic toxicity when added to SoC chemoradiation.” Prolonged and sustained survival was observed after experimental treatment with CAN-2409 in patients with borderline resectable PDAC (n=13) Estimated median overall survival was 28.8 months in the CAN-2409 group versus only 12.5 months in the control group. At 24 months, a survival rate of 71.4% was observed in CAN-2409 treated patients, after SoC chemoradiation and prior to surgery, versus only 16.7% in the control group. At 36 months, a survival rate of 47.6% was estimated in patients who received CAN-2409, together with SoC chemoradiation prior to surgery, versus only 16.7% in the control group. Importantly, 4 out of 7 patients who received CAN-2409 were still alive at the time of data cut-off, with 2 patients surviving more than 50.0 months from enrollment. Only 1 out of 6 patients, randomized to control SoC chemotherapy, remained alive at data cut-off (alive at 50.6 months). Previous analysis of blood and resected tumors showed consistent and robust activation of the immune response after experimental treatment with CAN-2409 In pancreatic tissue of patients treated with CAN-2409 plus prodrug together with SoC (but not SoC alone), dense aggregates of CD8+ granzyme B positive cytotoxic tumor infiltrating lymphocytes, dendritic cells, and B cells were observed in the tumor microenvironment. Increased levels of soluble granzymes B and H, as well as pro-inflammatory cytokines, including IFN-γ, were observed in peripheral blood after CAN-2409 administration, but not after SoC. CAN-2409 continued to be associated with a favorable safety/tolerability profile Addition of CAN-2409 regimen to SoC was generally well tolerated, with no dose-limiting toxicities, including no cases of pancreatitis “The failure of conventional immunotherapy to improve outcomes in pancreatic cancer is attributed to the highly immunosuppressive tumor microenvironment, which is largely devoid of immune cells,” said Paul Peter Tak, MD, PhD, FMedSci, President and Chief Executive Officer of Candel. “The immunological changes induced by CAN-2409, evident in the pancreatic tissue and the peripheral blood after administration, suggest that CAN-2409 is able to change the balance between the tumor and the patient’s anti-tumor immune response, which can convert progressive cancer into a chronic disease associated with improved survival.” Candel is a clinical stage biopharmaceutical company focused on developing off-the-shelf multimodal biological immunotherapies that elicit an individualized, systemic anti-tumor immune response to help patients fight cancer. Candel has established two clinical stage multimodal biological immunotherapy platforms based on novel, genetically modified adenovirus and herpes simplex virus (HSV) gene constructs, respectively. CAN-2409 is the lead product candidate from the adenovirus platform and is currently in ongoing clinical trials in non-small cell lung cancer (NSCLC) (phase 2), borderline resectable PDAC (phase 2), and localized, non-metastatic prostate cancer (phase 2 and phase 3). CAN-3110 is the lead product candidate from the HSV platform and is currently in an ongoing investigator-sponsored phase 1 clinical trial in recurrent high-grade glioma (rHGG). Finally, Candel’s enLIGHTEN™ Discovery Platform is a systematic, iterative HSV-based discovery platform leveraging human biology and advanced analytics to create new viral immunotherapies for solid tumors. This randomized, open-label phase 2 clinical trial is designed to evaluate the safety, preliminary efficacy, and biologic activity of a 2-3 injection regimen of CAN-2409 plus prodrug (valacyclovir or acyclovir) in patients with borderline resectable PDAC who are being treated with neoadjuvant chemoradiation prior to resection. After a protocol amendment in 2022, when enrollment of patients with locally advanced PDAC was discontinued, the clinical trial was designed to exclusively focused on borderline resectable disease. The clinical trial remains active but is not currently unrolling new patients. In a previously completed phase 1b clinical trial, a highly significant increase in the number of CD8+ tumor infiltration lymphocytes was demonstrated at the site of the tumor after CAN-2409 treatment. CAN-2409, Candel’s most advanced multimodal biological immunotherapy candidate, is an investigational off-the-shelf replication-defective adenovirus designed to deliver the herpes simplex virus thymidine kinase (HSV-tk) gene to a patient’s specific tumor and induce an individualized, systemic immune response against the disease. HSV-tk is an enzyme that locally converts orally administered valacyclovir into a toxic metabolite that kills nearby cancer cells. Together this regimen is designed to induce an individualized and specific CD8+ T cell mediated response against the injected tumor and uninjected distant metastases for broad anti-tumor activity, based on in situ vaccination against a variety of tumor antigens. Because of its versatility, CAN-2409 has the potential to treat a broad range of solid tumors. Encouraging monotherapy activity as well as combination activity with standard of care radiotherapy, surgery, chemotherapy, and immune checkpoint inhibitors have previously been shown in several preclinical and clinical settings. Furthermore, to date, more than 1,000 patients have been dosed with CAN-2409 with a favorable tolerability profile to date, supporting the potential for combination with other therapeutic strategies without inordinate concern of overlapping adverse events. Currently, Candel is evaluating the effects of treatment with CAN-2409 in NSCLC, borderline resectable PDAC, and localized, non-metastatic prostate cancer in ongoing clinical trials. CAN-2409, plus prodrug (valacyclovir), has been granted Fast Track Designation by the FDA for treatment of PDAC or stage III/IV NSCLC in patients who are resistant to first line PD-(L)1 inhibitor therapy and who do not have activating molecular driver mutations or have progressed on directed molecular therapy. The Company’s pivotal phase 3 clinical trial in prostate cancer is being conducted under a Special Protocol Assessment by FDA. Pancreatic cancer is a highly lethal malignancy, and is the fourth leading cause of cancer-related death in the United States among both men and women. Based on the National Cancer Institute, Surveillance, Epidemiology and End Results (SEER) database, pancreatic cancer is expected to account for 3.3% of all new cancer cases with an estimated 64,050 new cases and estimated 50,550 deaths in 2023. Effective therapeutics for pancreatic cancer, including PDAC, which accounts for 90% of all pancreatic carcinomas, are urgently needed. Surgical resection offers the only chance of cure, thus a major therapeutic goal for subjects with non-metastatic disease is to achieve complete tumor resection. Surgical treatment (pancreaticoduodenectomy, also known as the Whipple procedure) or total or distal pancreatectomy (depending on tumor location) is generally the recommended treatment for patients diagnosed with resectable cancer; the addition of adjuvant chemotherapy has been shown to only slightly improve survival rates (20 to 23 months). To this end, there has been increasing use of neoadjuvant chemotherapy and chemoradiation regimens for subjects with borderline resectable pancreatic ductal adenocarcinoma. Neoadjuvant regimens are intended to debulk the tumor, thereby increasing the proportion of patients who may become eligible for surgical resection and achieve complete resection (i.e., resection with negative margins, designated ‘R0 resection’). Unfortunately, even when an R0 resection is initially achieved, cures remain elusive as most patients experience disease recurrence due to residual micrometastatic disease. In a recent meta-analysis of 20 studies representing 283 patients with borderline resectable PDAC, neoadjuvant FOLFIRINOX with or without radiotherapy, median overall survival was only 22.2 months (95% CI, 18.8 to 25.6 months). Immunotherapy with PD-1 antibodies with or without CTLA-4 antibodies has been uniformly unsuccessful in patients with PDAC due to the dense stroma that surrounds PDAC tissue and the absence of tumor infiltrating lymphocytes. The content above comes from the network. if any infringement, please contact us to modify.

Clinical ResultImmunotherapyFast Track

27 Dec 2023

·www.globenewswire.com

Hyloris Announces Positive Clinical Study Results for Valacyclovir Oral Suspension (HY-029)

Valacyclovir is an Antiviral Medication that is Commonly Used to Treat Infections Caused by Herpes Viruses Clinical Study Demonstrates Comparable Relative Bioavailability to Valaciclovir Tablets under fasted conditions NDA submission1 (NDA) to the U.S. Food & Drug Administration (FDA) expected in 2024 December, 26 2023 -Hyloris Pharmaceuticals SA (Euronext Brussels: HYL), a specialty biopharma company committed to addressing unmet medical needs through reinventing existing medications, today announces positive results from a pivotal clinical study for its proprietary Valacyclovir Oral Suspension. It allows for further preparation of a NDA1 for submission to the FDA expected in 2024. Stijn Van Rompay, Chief Executive Officer of Hyloris, commented: “We are one step closer to bringing a new and improved mode of administration for this well-known molecule, prescribed more than 5 million times annually in the U.S2. Multiple benefits are to be expected from our novel formulation which addresses potential dosing inaccuracies associated with crushing tablets, aiming to enhance stability and storability, ultimately contributing to increased patient compliance and improved quality of life." The primary objective was to compare the proprietary Valacyclovir Oral Suspension (200 mg/mL) with Valtrex® tablets (50 mg/mL) prepared as an extemporaneous suspension3. The relative bioavailability of valacyclovir and acyclovir4 was measured after administration under fasted conditions5. In addition, the effect of food on the bioavailability of acyclovir after administration of proprietary Valacyclovir Oral Suspension (200 mg/mL) was assessed. Valacyclovir, currently commercialized as a solid oral in the U.S., is used to treat herpes virus infections, including herpes labialis (also known as cold sores), herpes zoster (also known as shingles), and herpes simplex (also known as genital herpes) in adults. For pediatric patients, the drug was approved for cold sores (herpes labialis) and chickenpox. Valacyclovir is available by prescription only, and the dosage and duration of treatment depend on the specific condition being treated and the individual patient's medical history. Estimates indicate 5,5 million prescriptions6 to over 2,4 million patients in the U.S. in 2020. In 2022 more than 560 million tablets were sold, growing at a CAGR of 5%7. Hyloris is a specialty biopharma company focused on innovating, reinventing, and optimizing existing medications to address important healthcare needs and deliver relevant improvements for patients, healthcare professionals and payors. Hyloris has built a broad, patented portfolio of 17 reformulated and repurposed value-added medicines that have the potential to offer significant advantages over available alternatives. Outside of its core strategic focus, the Company also has 1 approved high barrier generics product launched in the U.S. and 2 high barrier generic products in development. Two products are currently in initial phases of commercialization with partners: Sotalol IV for the treatment of atrial fibrillation, and Maxigesic® IV, a non-opioid post-operative pain treatment. The Company’s development strategy primarily focuses on the FDA’s 505(b)2 regulatory pathway, which is specifically designed for pharmaceuticals for which safety and efficacy of the molecule have already been established. This pathway can reduce the clinical burden required to bring a product to market, and significantly shorten the development timelines and reduce costs and risks. Hyloris is based in Liège, Belgium. For more information, visit www.hyloris.com and follow-us on LinkedIn. 1 After completion of the required stability and clinical activities. 2 Valacyclovir - Drug Usage Statistics, ClinCalc DrugStats Database. 3 An extemporaneous preparation (compound) is a drug or mixture of drugs prepared or compounded in a pharmacy according to the order of a prescriber. 4 Valacyclovir is nearly completely converted to acyclovir by first-pass metabolism. 5 The abstinence of food and drinks except water for a period of time prior to dosing. 6 Valacyclovir - Drug Usage Statistics, ClinCalc DrugStats Database. 7 Source: IQVIA. The content above comes from the network. if any infringement, please contact us to modify.

Drug ApprovalNDAClinical Result

13 Dec 2023

·www.globenewswire.com

Candel Therapeutics Receives FDA Fast Track Designation for CAN-2409 in Pancreatic Cancer

Candel Therapeutics, Inc. (Candel or the Company) (Nasdaq: CADL), a clinical stage biopharmaceutical company focused on developing multimodal biological immunotherapies to help patients fight cancer, today announced that the U.S. Food and Drug Administration (FDA) granted Fast Track Designation for its lead investigational adenovirus asset CAN-2409 plus prodrug (valacyclovir) for the treatment of patients with pancreatic ductal adenocarcinoma (PDAC) to improve overall survival. “We are pleased with the FDA's decision to grant Fast Track Designation for CAN-2409 in pancreatic cancer,” said Paul Peter Tak, MD, PhD, FMedSci, President and CEO of Candel. “This milestone follows our first interim data report from the randomized phase 2 clinical trial in patients with borderline resectable PDAC that showed prolonged and sustained survival after experimental treatment with CAN-2409, especially when compared to real-world data on patients receiving radiotherapy treatment. Candel remains on track to release updated overall survival data from the interim analysis of this clinical trial in the second quarter of 2024. We are grateful to the patients, caregivers, investigators and clinical sites that have taken part in this clinical trial.” In November 2023, the Company presented encouraging overall survival and immunological biomarker data based on an interim analysis of the randomized, phase 2 clinical trial of CAN-2409 plus prodrug together with standard of care (SoC) neoadjuvant chemoradiation followed by resection for borderline resectable non-metastatic PDAC at the Society for Immunotherapy of Cancer (SITC) Annual Meeting. An estimated survival rate of 71.4% at both 24 and 36 months in patients who received 2 or 3 injections of the CAN-2409 plus prodrug regimen, together with SoC chemoradiation prior to surgery was observed, versus only 16.7% estimated survival at both 24 and 36 months in patients treated with SoC chemoradiation prior to surgery alone. In parallel, the immunological changes observed in the resected pancreatic tissue after CAN-2409 administration suggested that this investigational treatment can activate an effective immunologic antitumoral response in this otherwise “cold” tumor. Candel is a clinical stage biopharmaceutical company focused on developing off-the-shelf multimodal biological immunotherapies that elicit an individualized, systemic anti-tumor immune response to help patients fight cancer. Candel has established two clinical stage multimodal biological immunotherapy platforms based on novel, genetically modified adenovirus and herpes simplex virus (HSV) gene constructs, respectively. CAN-3110 is the lead product candidate from the HSV platform and is currently in an ongoing investigator-sponsored phase 1 clinical trial in recurrent high-grade glioma (HGG). In addition, Candel’s enLIGHTEN™ Discovery Platform is a systematic, iterative HSV-based discovery platform leveraging human biology and advanced analytics to create new viral immunotherapies for solid tumors. CAN-2409 is the lead product candidate from the adenovirus platform and is currently in ongoing clinical trials in non-small cell lung cancer (NSCLC) (phase 2), borderline resectable pancreatic cancer (phase 2), and localized, non-metastatic prostate cancer (phase 2 and phase 3). This randomized, open-label phase 2 clinical trial is designed to evaluate the safety, preliminary efficacy, and biologic activity of a 2-3 injection regimen of CAN-2409 plus prodrug (valacyclovir or acyclovir) in patients with borderline resectable PDAC who are being treated with neoadjuvant chemoradiation prior to resection. After a protocol amendment in 2022, when enrollment of patients with locally advanced PDAC was discontinued, the clinical trial was designed to exclusively focused on borderline resectable disease. The clinical trial remains active but is not currently enrolling new patients. In a previously completed phase 1b clinical trial, a highly significant increase in the number of CD8+ tumor infiltration lymphocytes was demonstrated at the site of the tumor after CAN-2409 treatment. CAN-2409, Candel’s most advanced multimodal biological immunotherapy candidate, is an investigational off-the-shelf replication-defective adenovirus designed to deliver the herpes simplex virus thymidine kinase (HSV-tk) gene to a patient’s specific tumor and induce an individualized, systemic immune response against the disease. HSV-tk is an enzyme that locally converts orally administered valacyclovir into a toxic metabolite that kills nearby cancer cells. Together, this regimen is designed to induce an individualized and specific CD8+ T cell mediated response against the injected tumor and uninjected distant metastases for broad anti-tumor activity, based on in situ vaccination against a variety of tumor antigens. Because of its versatility, CAN-2409 has the potential to treat a broad range of solid tumors. Encouraging monotherapy activity as well as combination activity with standard of care radiotherapy, surgery, chemotherapy, and immune checkpoint inhibitors have previously been shown in several preclinical and clinical settings. Furthermore, to date, more than 950 patients have been dosed with CAN-2409 with a favorable tolerability profile to date, supporting the potential for combination with other therapeutic strategies without inordinate concern of overlapping adverse events. Currently, Candel is evaluating the effects of treatment with CAN-2409 in NSCLC, borderline resectable PDAC, and localized, non-metastatic prostate cancer in ongoing clinical trials. CAN-2409 has been granted Fast Track Designation by the FDA for treatment of PDAC or stage III/IV NSCLC in patients who are resistant to first line PD-(L)1 inhibitor therapy and who do not have activating molecular driver mutations or have progressed on directed molecular therapy. The Company’s pivotal phase 3 clinical trial in prostate cancer is being conducted under a Special Protocol Assessment by FDA. Pancreatic cancer is a highly lethal malignancy, and is the fourth leading cause of cancer-related death in the United States among both men and women. Based on the National Cancer Institute, Surveillance, Epidemiology and End Results (SEER) database, pancreatic cancer is expected to account for 3.3% of all new cancer cases, with an estimated 64,050 new cases and estimated 50,550 deaths in 2023.Effective therapeutics for pancreatic cancer, including PDAC, which accounts for 90% of all pancreatic carcinomas, are urgently needed. Surgical resection offers the only chance of cure, thus a major therapeutic goal for subjects with non-metastatic disease is to achieve complete tumor resection. Surgical treatment (pancreaticoduodenectomy, also known as the Whipple procedure) or total or distal pancreatectomy (depending on tumor location) is generally the recommended treatment for patients diagnosed with resectable cancer; the addition of adjuvant chemotherapy has been shown to only slightly improve survival rates (20 to 23 months). To this end, there has been increasing use of neoadjuvant chemotherapy and chemoradiation regimens for subjects with borderline resectable pancreatic ductal adenocarcinoma. Neoadjuvant regimens are intended to debulk the tumor, thereby increasing the proportion of patients who may become eligible for surgical resection and achieve complete resection (i.e., resection with negative margins, designated ‘R0 resection’). Unfortunately, even when an R0 resection is initially achieved, cures remain elusive as most patients experience disease recurrence due to residual micrometastatic disease. In a recent meta-analysis of 20 studies representing 283 patients with borderline resectable PDAC, neoadjuvant FOLFIRINOX with or without radiotherapy, median OS was only 22.2 months (95% CI, 18.8 to 25.6 months). Immunotherapy with PD-1 antibodies with or without CTLA-4 antibodies has been uniformly unsuccessful in patients with PDAC due to the dense stroma that surrounds PDAC tissue and the absence of tumor infiltrating lymphocytes. Fast Track Designation is a program designed to facilitate the development and expedite the review of medicines with the potential to treat serious conditions and fulfill an unmet medical need. An investigational medicine that receives Fast Track Designation may be eligible for more frequent interactions with the FDA to discuss the candidate’s development plan and, if relevant criteria are met, may be eligible for accelerated approval and priority review. The content above comes from the network. if any infringement, please contact us to modify.

ImmunotherapyFast TrackClinical Result

100 Deals associated with Acyclovir

External Link

KEGG	Wiki	ATC	Drug Bank
D00222	Acyclovir	D06BB03 J05AB01 S01AD03	DB00787

R&D Status

Approved

10 top approved records.

to view more data

Indication	Country/Location	Organization	Date
Keratitis, Herpetic	JP	Nitto Medic Co., Ltd.	23 Jan 2007
Herpes Labialis	US	Bausch Health US LLC	30 Dec 2002
Encephalitis, Herpes Simplex	AU	Pfizer Australia Pty Ltd.	19 Aug 1996
Varicella Zoster Virus Infection	AU	Pfizer Australia Pty Ltd.	19 Aug 1996
Chickenpox	US	Mylan Pharmaceuticals, Inc.	25 Jan 1985
Herpes Zoster	CN	Hubei Keyi Pharmaceutical Co., Ltd.	01 Jan 1985
Herpes Genitalis	US	Bausch Health US LLC	29 Mar 1982
Herpes Simplex	GB	Burroughs Wellcome	01 Jan 1981

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Indication	Highest Phase	Country/Location	Organization	Date
HIV Infections	Phase 3	US	Glaxo Wellcome SA	31 Aug 2001

Clinical Result

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT02073097 (CTgov)	Phase 1/2	Diffuse Large B-Cell Lymphoma	48	Pegfilgrastim+Acyclovir+carfilzomib+cyclophosphamide+Prednisone+doxorubicin hydrochloride+Vincristine sulfate+Rituximab	vovrtgxpis(uaxkhyxmfr) = pqnwrgemny djpkdfsrkh (hmtvufoywk, jmbkurpyte - xfbkoxhwvt) View more	-	29 May 2024
WCD2023	Not Applicable	Warts	-	Intralesional Acyclovir	jtwapgvcqu(lwdtwcnqiv) = blistering in 52.6% of the patients uehquwszfo (ujfbcvfndi ) View more	Positive	03 Jul 2023
				Intralesional saline
NCT04988646 (CTgov)	Not Applicable	-	56	Acyclovir (Acyclovir 200 mg Tablet)	ssaaxlmsme(jpnzpyjpgh) = eqvsfbmlxg gdlmlgmhux (bbogeqctlp, feotdbljvd - wpwnqkwscg) View more	-	08 Feb 2023
				Zovirax (Zovirax® 200 mg Tablet)	ssaaxlmsme(jpnzpyjpgh) = xlmpfwqqeg gdlmlgmhux (bbogeqctlp, notnnhdqqp - unvsofucsf) View more
IRCT20141124020073N2 (Pubmed)	Phase 3	Herpes Labialis	60	Acyclovir nanofiber patch	byrlmzihqj(baxnfmrvze) = lbundouqcv uuonyvgine (hafygdoytp ) View more	-	05 Dec 2021
				Placebo nanofiber patch	byrlmzihqj(baxnfmrvze) = shaqlaiebl uuonyvgine (hafygdoytp ) View more
NCT02265913 (CTgov)	Phase 3	Herpes Labialis	4,076	Acyclovir 5 percent (Perrigo) (Test Product)	mvhlnzwcjc(fizupqaifw) = tgnfscjatg vgxycjytmg (ylsgpinwna, jpwrbwdffv - mpgdzuzepc) View more	-	05 Jan 2021
				Acyclovir 5 percent (Reference) (Reference Product)	mvhlnzwcjc(fizupqaifw) = jgvdkgvrps vgxycjytmg (ylsgpinwna, hwehwzrmje - igqdcarcob) View more
NCT00495716 (CTgov)	Phase 4	Herpes Genitalis	72	acyclovir (Episodic Treatment Arm)	uhjrehptdk(ngkfhozyzt) = hasfbxltiy szzkalgnor (snsgiddmyu, izsatqgqvv - bfhhlraraz) View more	-	29 Jan 2020
				acyclovir (Suppressive Therapy Arm)	uhjrehptdk(ngkfhozyzt) = uijvnuqygd szzkalgnor (snsgiddmyu, oxrjdicagy - ewxuifupeh) View more
NCT02152358 (Pubmed \| JAMA Intern Med)	Phase 4	Herpesviridae Infections	238	Intravenous Acyclovir	xlcbzjqnfx(drczknccjd) = rywdeshxsn swftbvirrd (dbnfdgxhvl ) View more	Negative	16 Dec 2019
				Placebo	xlcbzjqnfx(drczknccjd) = pndmffdcqj swftbvirrd (dbnfdgxhvl ) View more
ASN2014	Not Applicable	Acute Kidney Injury	10	Acyclovir	gueqtvlutl(ltihprkbty) = lpyuhzexob mximeqowxk (wzltwbuuft ) View more	Positive	11 Nov 2014
				Acyclovir	gueqtvlutl(ltihprkbty) = casvhzghno mximeqowxk (wzltwbuuft ) View more
ASN2014	Not Applicable	Acute Kidney Injury diabetes	287	Intravenous Acyclovir	ayjwphmzfb(qtmdaxmutu) = udokvuttlt khkrtcdesz (gsgoueuklu )	Negative	11 Nov 2014
NCT00061945 (CTgov)	Phase 1/2	Philadelphia positive acute lymphocytic leukaemia \| Precursor T-Cell Lymphoblastic Leukemia-Lymphoma \| Adult Acute Lymphocytic Leukemia ... View more	302	Alemtuzumab (Phase I - Alemtuzumab and Combination Chemotherapy)	gnpxegbzgx(bkkjhwvwio) = ppwiugvgwu wybejgmrgk (lfbwqnbzib, eigfgiukdh - ocmlwnkllo) View more	-	16 Apr 2014
				Alemtuzumab (Phase II - Alemtuzumab and Combination Chemotherapy)	giadepdumk(tzyaazbsxv) = ackgtvpojq vhfwhcgnvd (mgwxqseuue, ttwhanbylg - jwbqtwptug) View more

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