PledPharma initiates clinical study on new treatment for paracetamol poisoning
PledPharma has recieved approval from the MHRA, the UK’s medicines regulatory body, to undertake a clinical trial for Aladote®, a new treatment for reducing liver damage from paracetamol (acetaminophen) poisoning. Paracetamol poisoning affects approximately 50,000 people the UK every year[i]. The trial will evaluate the safety and tolerability of Aladote® in combination with the current standard treatment (N-acetylcysteine) for the prevention of acute liver failure due to paracetamol poisoning.
Preclinical animal studies have suggested that Aladote® may be effective at reducing liver damage in the period more than eight hours after a paracetamol overdose, where N-acetylcysteine is minimally effective. The clinical study will be conducted in collaboration with the University of Edinburgh under the direction of Dr James Dear, Reader in Pharmacology at the University of Edinburgh, and specialist in paracetamol poisoning.
Paracetamol is the most commonly used drug in the world for the treatment of fever and pain, and is considered to be safe in therapeutic doses. However, toxic doses of more than four grams per day can cause severe, and sometimes fatal, liver damage. It is the drug most commonly taken in overdose in the UK[ii], and there are an estimated 50,000 emergency hospital admissionsi, and approximately 200 deaths[iii], due to paracetamol poisoning in the UK every year. Intentional overdose of paracetamol is the most common method for suicide attempts among adolescents aged 10-19 years. Many people also accidentally overdose on paracetamol, usually by taking multiple medicines without realising that they all contain paracetamol.
The current standard treatment for paracetamol poisoning is N-acetylcysteine, which is very effective at reducing liver damage in the period up to eight hours after an overdose. However, N-acetylcysteine’s efficacy drops off considerably after eight hours, becoming almost totally ineffective 24 hours after an overdose. Unfortunately, many paracetamol poisoning patients do not present at hospital until more than eight hours after their overdose, leaving them at considerable risk of severe liver damage. If the liver damage becomes too severe, the only remaining treatment option is a costly and invasive liver transplant. Promising preclinical data for calmangafodipir (active ingredient in Aladote®) has suggested that it may be effective at reducing liver damage from paracetamol in the period between eight and 24 hours after an overdose.
Dr James Dear, principal investigator and Reader in Pharmacology at the University of Edinburgh, commented, ˝During the first 24 hours after paracetamol poisoning people usually experience few or no symptoms. Therefore, many patients come to hospital at such a late stage that the current standard treatment is not sufficient to prevent acute liver failure. Calmangafodipir has in preclinical studies demonstrated impressive results even in the late stages of the poisoning process, and I look forward to leading the evaluation of the drug candidate in this important proof-of-principle study”.
PledPharma develops new drugs that protect the body against oxidative stress – a potentially debilitating and sometimes life-threatening condition that can be caused by chemotherapy treatment and following acetaminophen (paracetamol) overdose. The company’s most advanced project PledOx® is being developed to reduce nerve damage associated with chemotherapy. A phase IIb study has been conducted and will serve as the basis for the continued development. The drug candidate Aladote® is being developed to reduce the risk of acute liver failure associated with acetaminophen poisoning.
PledPharma (STO: PLED) is listed on Nasdaq First North. Erik Penser Bank is the company’s Certified Adviser (tel +46 8 463 80 00). For more information, see www.pledpharma.se
For more information, please contact:
Jacques Näsström, CEO, phone: +46 737 130 979
Michaela Gertz, CFO, phone: +46 709 26 17 75
[i] “Target biomarker profile for the clinical management of paracetamol overdose” http://onlinelibrary.wiley.com/doi/10.1111/bcp.12699/pdf
[ii] ”Death from paracetamol overdose despite appropriate treatment with n‐acetylcysteine” https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2658515/
[iii] ”Deaths related to drug poisoning in England and Wales: 2015 registrations” https://www.ons.gov.uk/peoplepopulationandcommunity/birthsdeathsandmarriages/deaths/bulletins/deathsrelatedtodrugpoisoninginenglandandwales/2015registrations#paracetamol-related-deaths-remain-stable-in-2015