Drug induced Liver Injury is responsible for up to 30+ of project terminations in clinical development. Me and my team are developing a personalized cell model to investigate individual DILI.
Recent Terminations include Lilly's LY2886721 which caused Liver Enzyme Elevations.
Has anyone information on some more terminated candidates and their commercial availability?
Dear Andreas, please check the attached literature (Journal of Applied Pharmaceutical Science 02 (05); 2012: 233-243) where you could find many drugs which causes DILI.
Also, you could check http://www.livertox.nih.gov/ web-site where you could find the hepatoxicity of the drugs on the market and the attached paper for drug-induced hepatoxicity where you could find the drugs recently withdrawn from the market due to the hepatoxicity.
Another web-site for withdrawn drugs and the reason of the withdrawals: http://www.ganfyd.org/index.php?title=Drug_withdrawals
Hepatoxic Drugs:
Statins and Other Lipid Lowering Drugs: Atorvastatin, Fluvastatin, Lovastatin, Pravastatin, Simvastatin, Fenofibrate, Gemfibrozil and Niacin; Oral Hypoglycemics: Acarbose, Pioglitazone, and Rosiglitazone; Anti-seizure Drugs: Carbamazepine, Felbamate, and Valproic Acid; Anti-fungal Drugs: Itraconazole, Ketoconazole, and Terbinafine; Drugs for Tuberculosis: Isoniazid, Pyrazinamide, and Rifampin; Immunosuppressants: Azathioprine, and Methotrexate; Antiretroviral Drugs: Ritonavir, Nevirapine; and others: Acetaminophen, Amiodarone, Diclofenac, Halothane, Leflunomide, Methyldopa.
Of course you could easily find the APIs (active pharmaceutical ingredients) which are hepatoxic but sold as a drug on the market. For the others, you could check commercial availability and sources from SciFinder. I use it very often and it is very helpful.
Best regards,
Esen
Dear Esen,
thanks a lot for your helpful hints. I'll try it
best regards
Andreas
Here is a recent news on Sovaprevir. Hope it is helpful to you.
FDA places clinical hold on sovaprevir
Achillion Pharmaceuticals has received notice from the FDA that a clinical hold has been placed on sovaprevirafter elevations in liver enzymes associated with significantly higher than anticipated exposure to atazanivirand sovaprevir was noted in a phase I drug-drug interaction study evaluating the effects of concomitant administration of sovaprevir with ritonavir-boosted atazanavir in healthy subjects. While conducting the drug-drug interaction study, Achillion detected unanticipated elevations in alanine aminotransferase (ALT) liver enzymes (grade 3 or 4) in multiple subjects, although none of these met the criteria for a serious adverse event. The company voluntarily stopped further dosing in the study and notified the FDA of these findings. Preliminary pharmacokinetic results indicate a metabolic interaction whereby plasma concentrations of both atazanavir and sovaprevir were substantially increased upon coadministration. Such ALT elevations have not been seen in any other drug-drug interaction studies completed with sovaprevir to date. With the preliminary draft data on hand at the time of notification, the FDA placed sovaprevir on clinical hold. In order to resolve the clinical hold, the FDA has asked for study reports from two drug-drug interaction studies and an integrated safety analysis of ongoing sovaprevir trials, each of which Achillion expects to provide to the FDA within approximately 6 weeks. The FDA has allowed continued enrollment and treatment of patients in the phase II trial evaluating 12 weeks of sovaprevir in combination with ACH-3102 and ribavirin for patients with treatment-naive genotype 1 hepatitis C virus infection (ClinicalTrials.gov Identifier NCT01849562). The company plans to release interim clinical trial results from that study during the third and fourth quarter of this year (Achillion Pharmaceuticals News Release).
Thank you for this very up to date information!
Do you know any other recently abandoned projects?
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