The translational safety intelligence portal

Phase III study of upadacitinib (JAK1 inhibitor; 15 or 30 mg PO qd) in patients with Crohn’s disease. The most common adverse events (AEs) in the upadacitinib arms were exacerbation of Crohn’s disease, arthralgia and pyrexia. Malignancies (excluding non-melanoma skin cancer) were reported in 2 patients on upadacitinib 30 mg and 1 patient on upadacitinib 15 mg. 1 patient on upadacitinib 30 mg reported an adverse event of hepatic vein thrombosis. [Data from an AbbVie communication announcing topline results from a phase III study of upadacitinib in patients with moderate to severe Crohn’s disease] Company Communication

Phase Ib study of alofanib (FGFR2 inhibitor; 50-350 mg/m2 IV) patients with advanced and metastatic gastric adenocarcinoma. Grade 3-4 treatment-related adverse events included increased ALT/AST and neutropenia at 50 mg/m2; diarrhea and headache at 165 mg/m2; and increased serum amylase and reactions immediately after injection (listed) at 350 mg/m2. Congress Alert

Pilot safety study of ONM-501 (STING agonist) for oncology immunotherapy. Mice treated with ONM-501 did not exhibit systemic cytokine storm or changes in body weight, ALT, AST, blood urea nitrogen or creatinine levels. Congress Alert

The FDA has updated the product information of Apokyn (apomorphine hydrochloride; dopamine receptor agonist), adding warnings for hemolytic anemia requiring hospitalization. Several cases included positive direct Coombs’s test, suggesting a potential immune-mediated hemolysis. Regulatory Agency Communication

Phase I study of KT-474 (IRAK4 degrader; 25-1,600 mg PO) in patients with atopic dermatitis or hidradenitis suppurativa. Treatment-emergent adverse events were headache (5/36 patients), palpitations (3) and nausea (2). [Data from a Kymera Therapeutics presentation, May 2022] Company Communication

Swissmedic has issued a communication evaluating reports of suspected adverse drug reactions to COVID-19 vaccines in Switzerland. The most common adverse reactions (ARs) associated with Spikevax, Comirnaty and the Janssen COVID-19 vaccine are pyrexia, headache and fatigue. Cases of acute or chronic urticaria have been frequently reported after booster vaccinations with Spikevax. 407 cases of myocarditis and/or pericarditis with a suspected link to vaccinations have been reported in Switzerland, including 301 reports with Spikevax, 90 with Comirnaty and 4 with the Janssen COVID-19 vaccine. Other ARs are listed. Regulatory Agency Communication

The special warnings and precautions for use section of the EMA EPAR for Padcev indicates that it may cause skin reactions (including maculopapular rash, Stevens-Johnson syndrome and toxic epidermal necrolysis); hyperglycemia and diabetic ketoacidosis; peripheral neuropathy (predominantly peripheral sensory neuropathy); ocular disorders (including dry eye); infusion-site extravasation resulting in skin and soft tissue injury; and embryo-fetal toxicity. [Data from EMA European public assessment report for Padcev (enfortumab vedotin; nectin-4/tubulin polymerization inhibitor)] Regulatory Agency Communication

The special warnings and precautions for use section of the EMA EPAR for Tepmetko indicates that it may cause interstitial lung disease and pneumonitis; increase in ALT and/or AST; QTc prolongation; and embryo-fetal toxicity. Other adverse events are listed. [Data from EMA European public assessment report for Tepmetko (tepotinib; Met inhibitor)] Regulatory Agency Communication

The Singapore Health Sciences Authority (HSA) has issued a safety communication warning about the risk of aseptic meningitis with amoxicillin (bacterial penicillin-binding protein inhibitor). To date, 1 case of aseptic meningitis possibly related to amoxicillin/clavulanic acid has been reported to the HSA. The package insert of amoxicillin-containing products will be updated to include amoxicillin-induced aseptic meningitis. [Data from HSA ADR News Bulletin 2022 May] Regulatory Agency Communication

Phase IIa clinical trial of PRAX-944 (Cav3 blocker; up to 120 mg) in patients with essential tremor. The most common treatment-emergent adverse events (TEAEs) were constipation (6/14 patients), dizziness (4), fatigue (3), cognitive disorder, headache, insomnia and paresthesia (2 each). Other TEAEs are listed. [Data from a Praxis Precision Medicines presentation reporting results from an open-label study of PRAX-944] Company Communication

LogicBio Therapeutics communication announcing that the FDA has lifted the clinical hold on the phase I/II study of LB-001 (methylmalonyl-CoA mutase gene therapy) after the two reported cases of serious thrombotic microangiopathy were resolved. The company also modified the trial protocol to enhance monitoring measures against this adverse reaction. Company Communication

The FDA has limited the authorized use of Janssen COVID-19 vaccine following an updated analysis of the risk of thrombosis with thrombocytopenia syndrome (TTS) associated with this vaccine. The vaccine is now available to subjects aged ≥18 years for whom other authorized or approved COVID-19 vaccines are not accessible or clinically appropriate, and those who elect to receive the vaccine because they would otherwise not receive a COVID-19 vaccine. The FDA has updated the product information of Janssen COVID-19 vaccine to include a warning statement about the risk of TTS. Regulatory Agency Communication

Myovant Sciences and Pfizer communication announcing that the FDA has extended the review period for the supplemental New Drug Application for MYFEMBREE (estradiol/norethindrone acetate/relugolix) for the management of moderate-to-severe pain associated with endometriosis. The agency has required extended time to review additional information from the companies regarding bone mineral density. Company Communication

The Therapeutic Goods Administration (TGA) has commissioned an independent expert report on the risks of self-harm from intentional paracetamol misuse in relation to the current access controls for paracetamol. The report will include the incidence of overdosing reports, emergency department presentations, hospital admissions, adverse health outcomes and deaths attributable to paracetamol. Regulatory Agency Communication