PledOx (calmangafodipir) / Egetis Therap, Solasia, Maruho - LARVOL DELTA

Recent Advances in Diagnosis, Management, Treatment, and Prevention of Neuropathies in Cancer Patients. (PubMed, Curr Neurol Neurosci Rep) - "Though calmangafodipir was negative for preventing peripheral neuropathy in oxaliplatin-based treatments, the POLAR trial randomizing patients to cooling or compression of the dominant hand during taxane administration significantly reduced incidence of chemotherapy-induced peripheral neuropathy. As of yet, there are no treatments for chemotherapy-induced peripheral neuropathy, but continued basic research into the SARM pathway is likely to yield novel agents that will stop, or prevent, the process."

Journal • Review • Oncology • Pain • NEFL

Paclitaxel-induced peripheral neuropathy in male rats attenuated by calmangafodipir, a superoxide dismutase mimetic. (PubMed, J Pharmacol Sci) - "Conversely, calmangafodipir (1-10 mg/kg, intravenous, thrice weekly for 4 weeks) prevented mechanical allodynia and axonal degeneration induced by paclitaxel. These results suggest that calmangafodipir may inhibit paclitaxel-induced peripheral neuropathy."

Journal • Preclinical • Pain

First Report of Leaf Spot Caused by Alternaria alternata on Artemisia stolonifera (Maxim) Komar. in China. (PubMed, Plant Dis) - "PP101993 and PQ458469; PP350760 and PQ45545; PP409573 and PQ474679; PP746506 and PQ474680; PP375820 and PQ458468; PQ001738 and PQ458467 for JNCO1 and JNC02 respectively...alternata causing leaf spot on Ar. stolonifera in China and provides vital information on the pathogen for further diagnosis and management of the disease."

Journal • GAPDH

First report of Lasiodipilodia theobromae Causing leaf spot of Agave sisalana in GuangXi, China. (PubMed, Plant Dis) - "The ITS (PP209594), TEF-1α (PP234629), and TUB (PP234628) sequences of representative isolate JM01 were deposited in GeneBank...theobromae is primarily a plant pathogen that causes rotting and dieback in fruits and plants in tropical and subtropical regions (Puttanna 1967). This study is useful to focus on management strategies for leaf rot disease by L. theobromae of A. sisalana."

Journal

Comments on "Clinically relevant therapeutic approaches against acetaminophen (APAP) hepatotoxicity and acute liver failure". (PubMed, Biochem Pharmacol) - No abstract available

Journal • Hepatology • Liver Failure

Manganese- and Platinum-Driven Oxidative and Nitrosative Stress in Oxaliplatin-Associated CIPN with Special Reference to Ca4Mn(DPDP)5, MnDPDP and DPDP. (PubMed, Int J Mol Sci) - "Recently, hope has been raised regarding the catalytic antioxidants mangafodipir (MnDPDP) and calmangafodipir [Ca4Mn(DPDP)5; PledOx®], which by mimicking mitochondrial manganese superoxide dismutase (MnSOD) may be expected to overcome oxaliplatin-associated chemotherapy-induced peripheral neuropathy (CIPN)...However, pharmacokinetic considerations suggest that the efficacy of MnDPDP on Pt2+-associated neurotoxicity depends on another action of this drug. Electron paramagnetic resonance (EPR) studies have demonstrated that Pt2+ outcompetes Mn2+ and endogenous Zn2+ in binding to fodipir (DPDP), hence suggesting that the previously reported protective efficacy of MnDPDP against CIPN is a result of chelation and elimination of Pt2+ by DPDP, which in turn suggests that Mn2+ is unnecessary for efficacy when it comes to oxaliplatin-associated CIPN."

Journal • Review • Cardiovascular • Colorectal Cancer • Gastrointestinal Cancer • Myocardial Infarction • Oncology • Pain • Solid Tumor • SOD2

First Report of Pitaya Virus X Infecting Lophocereus schottii f. mieckleyanus (Thin-Stemmed Totem Pole Cactus) in the United States. (PubMed, Plant Dis) - "Sequences of isolates YPHC-61A and YPHC-61B were submitted in the GenBank under accession numbers, OQ915350 and PP182358 (CP gene) and OQ915351 and PP209539 (RdRp gene)...2018) and dragon fruit (Selenicereus undatus) plants in South Korea (Bae and Park 2022). To our knowledge, this is the first report of PiVX on L. schottii f. mieckleyanus in the United States and worldwide."

Journal • Infectious Disease

Clinically relevant therapeutic approaches against acetaminophen hepatotoxicity and acute liver failure. (PubMed, Biochem Pharmacol) - "This review will discuss the background, mechanisms of action, and the clinical prospects of the existing FDA-approved antidote N-acetylcysteine, of several new drug candidates under clinical development [4-methylpyrazole (fomepizole), calmangafodipir] and examples of additional therapeutic targets (Nrf2 activators) and regeneration promoting agents (thrombopoietin mimetics, adenosine A2B receptor agonists, Wharton's Jelly mesenchymal stem cells). The substantial progress in the understanding of the pathophysiology of APAP hepatotoxicity led to the consideration of several drugs for development as clinical antidotes against APAP overdose in recent years. Based on the currently available information, it is likely that this will result in additional drugs that could be used as adjunct treatment for N-acetylcysteine."

Journal • Review • Hepatology • Liver Failure

Exacerbated Neuropathy in POLAR A and M Trials Due to Redox Interaction of PledOx-Associated Mn and Oxaliplatin-Associated Pt. (PubMed, Antioxidants (Basel)) - "FOLFOX6, oxaliplatin in combination with 5-fluorouracil (5-FU), possesses superior tumoricidal activity in comparison to 5-FU alone, but suffers seriously from dose-limiting platinum-associated Chemotherapy-Induced Peripheral Neuropathy (CIPN). For use as a therapeutic adjunct in rescue treatment, like in ischemia-reperfusion of the heart or other organs, or in acetaminophen (paracetamol)-associated liver failure, there is little or nothing speaking against the use of PledOx or other PLED compounds. However, this must be thoroughly documented in more carefully designed clinical trials."

Journal • Cardiovascular • Colorectal Cancer • Gastrointestinal Cancer • Hepatology • Liver Failure • Oncology • Pain • Reperfusion Injury • Solid Tumor

PP100-01 (calmangafodipir) for overdose of paracetamol (The POP trial): Principal results (EASL-ILC 2019) - P1; "PP100-01 was tolerated in patients treated with NAC for APAP overdose and may reduce liver injury. Clinicaltrials.gov NCT03177395Funder: PledPharma AB"

The Global POLAR program: Calmangafodipir used on top of modified FOLFOX6 (5-FU/FA and oxaliplatin) to prevent chemotherapy induced peripheral neuropathy (CIPN). (ASCO-GI 2019) - P3; "NCT03654729; Background: Oxaliplatin (OXA), is approved in combination with 5-FU/FA (5-fluorouracil/folinic acid; FOLFOX) for metastatic as well as in adjuvant colo-rectal cancer (CRC) treatment. In the POLAR A study Disease Free Survival is one additional safety endpoint assessed. Results are expected during second half of 2020."

Clinical

Calmangafodipir for Prevention of Oxaliplatin-Induced Peripheral Neuropathy: Two Placebo-Controlled, Randomized Phase 3 Studies (POLAR-A/POLAR-M). (PubMed, JNCI Cancer Spectr) - P3 | "The POLAR clinical studies failed to meet their primary endpoint. These results highlight the challenges of targeting oxidative stress for preventing CIPN in both the adjuvant and metastatic settings."

Journal • P3 data • Colorectal Cancer • Gastrointestinal Cancer • Immunology • Oncology • Pain • Solid Tumor

Digital smartphone intervention to recognise and manage early warning signs in schizophrenia to prevent relapse: the EMPOWER feasibility cluster RCT. (PubMed, Health Technol Assess) - "A main trial with a sample size of 500 (assuming 90% power and 20% dropout) would detect a clinically meaningful reduction in relapse (relative risk 0.7) and improvement in other variables (effect sizes 0.3-0.4)."

Clinical • Journal • CNS Disorders • Psychiatry • Schizophrenia

Novel Therapies for the Treatment of Drug-Induced Liver Injury: A Systematic Review. (PubMed, Front Pharmacol) - "Investigated agents included: bicyclol, calmangafodipir, cytisin amidophospate, fomepizole, livina-polyherbal preparation, magnesium isoglycyrrhizinate (MgIG), picroliv, plasma exchange, radix Paeoniae Rubra, and S-adenosylmethionine...More effort should be involved to investigate the novel treatment of DILI. Well-designed RCTs with appropriate sample sizes, comparable groups and precise, not only surrogate outcomes are urgently welcome."

Journal • Review • Hepatology • Inflammation • Liver Failure

The Damaging Outcome of the POLAR Phase III Trials Was Due to Avoidable Time-Dependent Redox Interaction between Oxaliplatin and PledOx. (PubMed, Antioxidants (Basel)) - "However, when it comes to the POLAR trials, PledOx was administered, for incomprehensible reasons, "on Top of Modified FOLFOX6" at day one, i.e., after the two-hour oxaliplatin infusion instead of before oxaliplatin. This is a time point when the plasma concentration of oxaliplatin and Pt-metabolites is at its highest, and where the risk of devastating redox interactions between PledOx and oxaliplatin, in turn, is at its highest."

Journal • P3 data • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Pain • Solid Tumor

Preventive Treatment of Oxaliplatin Induced Peripheral Neuropathy in Metastatic Colorectal Cancer (POLAR-M) (clinicaltrials.gov) - P3; N=291; Terminated; Sponsor: Egetis Therapeutics; Completed ➔ Terminated; On 23 January 2020, the Sponsor announced that the United States (US) Food and Drug Administration (FDA) had issued a clinical hold in the US of the POLAR program.

Clinical • Trial termination • Colon Cancer • Colorectal Adenocarcinoma • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Pain • Solid Tumor • MRI

Business Overview of Pipeline Products (Third Quarter of the Fiscal Year Ending December 31, 2021) (Market Screener) - "Solasia Pharma K.K...today announced its Consolidated Financial Results for the Nine Months of the Fiscal Year Ending December 31, 2021....The Company confirmed that the primary endpoint of the Global Phase III clinical trial of PledOx® targeting oxaliplatin-induced peripheral neuropathy conducted in Japan, South Korea, Taiwan and Hong Kong, in addition to the US and EU, had not been achieved...Based on the results of the above-mentioned trial, the Company decided to park the development for a platinum-based agent, oxaliplatin-induced peripheral neuropathy; instead, is conducting additional animal studies to investigate the product’s potential in targeting taxane-induced peripheral neuropathy."

P3 data • Preclinical • CNS Disorders • Neuralgia • Pain • Peripheral Neuropathic Pain

The Global POLAR program: Calmangafodipir used on top of modified FOLFOX6 (5-FU/FA and oxaliplatin) to prevent chemotherapy induced peripheral neuropathy (CIPN). (ASCO-GI 2019) - P3; "NCT03654729; Background: Oxaliplatin (OXA), is approved in combination with 5-FU/FA (5-fluorouracil/folinic acid; FOLFOX) for metastatic as well as in adjuvant colo-rectal cancer (CRC) treatment. In the POLAR A study Disease Free Survival is one additional safety endpoint assessed. Results are expected during second half of 2020."

Clinical

"PledOxのESMOって ESMO2021(9/16-21) じゃなくて ESMO World GI(6/30-7/3)か #WorldGI2021 https://t.co/pENcHAqXPd 知らんやん 見つからないからESMO2021を片っ端から探してたよ pledめ!!!" (@neko_nekodayo)

Gastrointestinal Cancer

POLAR-A: Preventive Treatment of OxaLiplatin Induced peripherAl neuRopathy in Adjuvant Colorectal Cancer (clinicaltrials.gov) - P3; N=280; Recruiting; Sponsor: PledPharma AB

Clinical • New P3 trial • Colon Cancer • Colorectal Adenocarcinoma • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Pain • Solid Tumor • CEACAM5

POLAR-A: Preventive Treatment of OxaLiplatin Induced peripherAl neuRopathy in Adjuvant Colorectal Cancer (clinicaltrials.gov) - P3; N=301; Completed; Sponsor: PledPharma AB; Active, not recruiting ➔ Completed

Clinical • Trial completion • Colon Cancer • Colorectal Adenocarcinoma • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Pain • Solid Tumor • CEACAM5

POLAR-A: Preventive Treatment of OxaLiplatin Induced peripherAl neuRopathy in Adjuvant Colorectal Cancer (clinicaltrials.gov) - P3; N=301; Active, not recruiting; Sponsor: PledPharma AB; Recruiting ➔ Active, not recruiting

Clinical • Enrollment closed • Colon Cancer • Colorectal Adenocarcinoma • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Pain • Solid Tumor • CEACAM5

POLAR-A: Preventive Treatment of OxaLiplatin Induced peripherAl neuRopathy in Adjuvant Colorectal Cancer (clinicaltrials.gov) - P3; N=301; Active, not recruiting; Sponsor: PledPharma AB; Trial completion date: Nov 2021 ➔ Sep 2020

Clinical • Trial completion date • Colon Cancer • Colorectal Adenocarcinoma • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Pain • Solid Tumor • CEACAM5

Nicotine replacement treatment, e-cigarettes and an online behavioural intervention to reduce relapse in recent ex-smokers: a multinational four-arm RCT. (PubMed, Health Technol Assess) - "Recruiting recent ex-smokers into an interventional study proved problematic. Both interventions were well received and safe. Combining the interventions did not surpass the effects of each intervention alone. There was a trend in favour of single interventions reducing relapse, but it did not reach significance and there are reasons to interpret the trend with caution."

Journal • Tobacco Cessation

Preventive Treatment of Oxaliplatin Induced Peripheral Neuropathy in Metastatic Colorectal Cancer (POLAR-M) (clinicaltrials.gov) - P3; N=291; Completed; Sponsor: PledPharma AB; Active, not recruiting ➔ Completed

Clinical • Trial completion • Colon Cancer • Colorectal Adenocarcinoma • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Pain • Solid Tumor