Ingavirin (imidazolyl ethanamide pentandioic acid) / Myelo Therap, Valenta Pharm - LARVOL DELTA

Correlation of a four gene set with H-ARS severity in irradiated minipigs treated with Myelo001. (PubMed, Int J Radiat Biol) - "This independent minipig study confirms previous work showing that these genes do not exhibit statistically significant radiation-responsiveness in this animal model. Under the experimental conditions applied, no significant age or sex related changes nor treatment-related effects of Myelo001 were observed, which may reflect model-specific limitations or a lack of efficacy in this setting, or a combination of both."

Journal • Hematological Disorders • Hematological Malignancies • Leukemia • Oncology • DDB2 • FDXR • POU2AF1 • WNT3

Safety and Pharmacokinetics of Ingavirin Forte, Capsules, 90 mg + 20 mg (Valenta Pharm JSC, Russia) Compared With Ingavirin, Capsules, 90 mg, Under Fasting and Fed Conditions. (clinicaltrials.gov) - P1 | N=36 | Recruiting | Sponsor: Valenta Pharm JSC

New P1 trial • Infectious Disease • Influenza • Respiratory Diseases

Pharmacokinetics, pharmacodynamics, and radiomitigative efficacy of IEPA in a non-human primate model of acute radiation syndrome. (PubMed, Int J Radiat Biol) - "Imidazolyl ethanamide pentandioic acid (IEPA), a novel orally bioavailable small molecule, has demonstrated radioprotective effects in rodent models earlier...These results indicate that IEPA has the potential to be further investigated as a MCM for ARS. To continue toward a clinical development path, the confirmation of the presented results with a study design adequately powered to assess a drug-mediated survival benefit is needed."

Journal • PK/PD data • Preclinical • Hematological Disorders

Study to Evaluate the Efficacy, Safety, and Tolerability of the Ingavirin Forte Capsules (Valenta Pharm JSC) at Different Doses in Subjects With Influenza and Other Acute Respiratory Viral Infections. (clinicaltrials.gov) - P2 | N=300 | Recruiting | Sponsor: Valenta Pharm JSC

New P2 trial • Infectious Disease • Influenza • Respiratory Diseases

Imidazolyl ethanamide pentandioic acid promotes hematopoietic recovery following sublethal radiation in a murine model. (PubMed, Int J Radiat Biol) - "Our results reveal that IEPA attenuated radiation-induced DNA damage and improved recovery of HSCs/HPCs, myeloid as well as lymphoid progenitors, accompanied by increases in platelets in blood, megakaryocytes in BM and splenic CD34+ cells. IEPA shows promise as a radiation mitigator, with no significant benefit observed from adding GM-CSF."

Journal • Preclinical • Hematological Disorders • Infectious Disease • CD34 • CSF2 • FOXM1 • H2AX

Safety, Tolerability, and Pharmacokinetic Parameters of Increasing Doses of Ingavirin Forte, Capsules, During Single and Subsequent Multiple Oral Administration in Healthy Volunteers (clinicaltrials.gov) - P1 | N=36 | Recruiting | Sponsor: Valenta Pharm JSC

New P1 trial • Infectious Disease • Influenza • Respiratory Diseases

IEPA, a novel radiation countermeasure, alleviates acute radiation syndrome in rodents. (PubMed, Int J Radiat Biol) - "IEPA (imidazolyl ethanamide pentandioic acid) is an orally bioavailable small molecule pseudopeptide with myeloprotective properties, a good clinical safety profile, and stable chemical characteristics facilitating stockpiling...IEPA treatment is compatible with Neulasta® (Pegfilgrastim; PEG-G-CSF); adequately powered studies are needed to confirm the trend toward improved survival over standard care alone. IEPA is a promising development candidate as a medical countermeasure against the effects of acute radiation syndrome. Further confirmatory studies in small and large animal models should validate the robustness and translatability of preliminary rodent data on IEPA's radiomitigative efficacy."

Journal • Preclinical • Hematological Disorders

Efficacy and Safety of Ingavirin®, Capsules, 60 mg, in Children With Influenza and Other Acute Respiratory Viral Infections (clinicaltrials.gov) - P4 | N=80 | Recruiting | Sponsor: Valenta Pharm JSC

New P4 trial • Infectious Disease • Influenza • Respiratory Diseases

Imidazolyl Ethanamide Pentandioic Acid (IEPA) as Potential Radical Scavenger during Tumor Therapy in Human Hematopoietic Stem Cells. (PubMed, Molecules) - "Treatment with IEPA was followed by irradiation (IR) or chemotherapy (ChT; cisplatin, CIS; lomustine, CCNU; temozolomide, TMZ). The IR- or ChT-induced decline of early progenitors could not be reversed by IEPA. Our data indicate that IEPA is a potential candidate for the prevention of hematologic toxicity in cancer treatment without affecting therapeutic benefits."

Journal • Brain Cancer • CNS Tumor • Glioblastoma • Head and Neck Cancer • Hematological Disorders • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • Thrombocytopenia

Computational medicinal chemistry role in clinical pharmacy education: Ingavirin for coronavirus disease 2019 (COVID-19) discovery model. (PubMed, Pharm Pract (Granada)) - "UCSF chimera showed viral spike protein elements binding to ACE2 retained in the best ingavirin pose in SwissDock at 1.75 Angstroms. Ingavirin has a promising inhibitory potential to host (ACE2 and nCoV spike protein) recognition, and hence could offer the next best mitigating effect against the current coronavirus disease (COVID-19) pandemic."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Insight into the Hantaan virus RNA-dependent RNA polymerase inhibition using in-silico approaches. (PubMed, Mol Divers) - "The docking studies showed that peramivir, and ingavirin compounds can effectively bind with the manganese ions and engage with other active site residues of this protein. Simulation analysis showed that they were in constant contact with the active site manganese ions and amino acid residues of the HTN virus endonuclease domain. This study will help in better understanding the HTN and related viruses."

Journal • Hematological Disorders • Nephrology • Renal Disease

Pharmacoepidemiological research of COVID-19 in the Russian Federation EGIDA-2020 (PubMed, Ter Arkh) - "Umifenovir therapy and inclusion of interferon in AVT regimens was associated improvement in the clinical manifestation of the disease among patients."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

COMBINATION OF IMIDAZOLYL ETHANAMIDE PENTANDIOIC ACID AND PEGFILGRASTIM FOR THE TREATMENT OF CHEMOTHERAPY-INDUCED MYELOSUPPRESSION (MASCC-ISOO 2022) - "Methods CD-1 mice, exposed to a single Cyclophosphamide injection (200 mg/kg b.w., i.p.), were treated daily with IEPA (100 mg/kg b.w., p.o.) for 5 days, alone or in combination with a single dose Peg-G-CSF (0.1 mg/kg b.w., s.c.) (Figure 1). Conclusions Oral IEPA treatment in combination with Peg-G-CSF provides a faster or equivalent time of recovery of immune cells compared to Peg-G-CSF alone. IEPA will be further investigated as a supportive care candidate in RT-CTX settings."

Hematological Disorders • Infectious Disease • CSF3

Efficacy and Safety of Ingavirin®, Syrup, 30 mg/5 ml, in Children With Influenza and Other Acute Respiratory Viral Infections (clinicaltrials.gov) - P3 | N=284 | Recruiting | Sponsor: Valenta Pharm JSC

New P3 trial • Infectious Disease • Respiratory Diseases

Efficacy and Safety of Ingavirin®, 90 mg Capsules in Patients With COVID-19 (clinicaltrials.gov) - P3 | N=290 | Recruiting | Sponsor: Valenta Pharm JSC

New P3 trial • Infectious Disease • Novel Coronavirus Disease

[VIRTUAL] IMIDAZOLYL ETHANAMIDE PENTANDIOIC ACID (IEPA, MYELO001) FOR THE TREATMENT OF RADIATION- INDUCED MYELOSUPPRESSION (MASCC-ISOO 2021) - "Conclusions Oral IEPA treatment mitigated IR-induced hematotoxicity and, under high IR up to 6 Gy, increased survival. With its good safety and tolerability profile, IEPA is a promising supportive care candidate for further investigation as a mitigator of myelosuppression caused by RT-CTX regimens and radiopharmaceuticals."

Hematological Disorders • Infectious Disease • Neutropenia

Pharmacotherapy for acute respiratory infections caused by influenza viruses: current possibilities (PubMed, Ter Arkh) - "An adequate choice of pharmacotherapy tools should be based on high efficiency and safety of drugs, with a possible reduction in such negative factors as polypharmacy. This review includes comparative pharmacological characteristics of drugs with activity against RNA viruses, along with parameters of their clinical efficacy."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases