The translational safety intelligence portal

First-in-human phase I study of the antibody-drug conjugate MRG-002 (HER2/tubulin polymerization inhibitor; 0.3-3 mg/kg) in 25 patients with advanced or metastatic solid tumors. The most common treatment-related adverse events (TRAEs) were neutrophil count decrease, AST increase, white blood cell count decrease (56% patients each), lactate dehydrogenase increase, alopecia (44% each), CPK increase (40%), ALT increase (36%), triglyceride increase, cholesterol increase, GGT increase, appetite decrease and hypoesthesia (32% each). Grade ≥3 TRAEs included neutrophil count decrease and triglyceride increase (12% each). Other TRAEs are listed Congress Alert

Phase II/III study evaluating the efficacy and safety of SCB-2019 (Clover COVID-19 vaccine; 30 mcg IM) in 30,128 participants. Common adverse events (AEs) included injection-site pain, fatigue and headache. Other AEs are listed. [Data from a Clover Biopharmaceuticals presentation summarizing results from the SPECTRA trial] Company Communication

The FDA has updated the product information of Cabometyx (cabozantinib S-malate; AXL/Met/VEGFR-2 inhibitor), adding warnings about thyroid dysfunction (including hypothyroidism) and hypocalcemia. The “Adverse Reactions” section has also been updated to include novel safety data from a clinical study evaluating Cabometyx for the treatment of thyroid cancer. Pleural effusion, fatal arterial hemorrhage, dry mouth, LDH increase, and decreased leukocytes and neutrophils have been added. Regulatory Agency Communication

Tivdak carries a black box warning for alterations in the corneal epithelium and conjunctiva resulting in changes in vision, such as severe vision loss and corneal ulceration. [Data from FDA approved drug report for Tivdak (tisotumab vedotin-tftv; coagulation factor III/tubulin polymerization inhibitor)] Regulatory Agency Communication

Conclusions from a Periodic Safety Update Report of Veklury (remdesivir; viral RNA polymerase inhibitor). Based on data from spontaneous reports, a causal relationship between remdesivir and sinus bradycardia is considered at least a reasonable possibility. The drug’s product information will be updated to include sinus bradycardia as an undesirable effect with frequency “unknown”. Regulatory Agency Communication

The EMA has recommended marketing authorization be refused for Raylumis (tanezumab; nerve growth factor inhibitor) for the treatment of chronic pain of the hip or knee in patients with osteoarthritis. The agency considered that, in comparison with the current therapies, Raylumis did not show any improvement in pain relief and physical functioning. In addition, patients on Raylumis had an increased risk of side effects, such as rapid progressive osteoarthritis. [Data from EMA summary of opinion for Raylumis] Regulatory Agency Communication

The most common side effects of Gavreto (pralsetinib; RET inhibitor) are anemia, increased ALT/AST, neutropenia, constipation, musculoskeletal pain, fatigue, leukopenia and hypertension. [Data from EMA summary of opinion for Gavreto] Regulatory Agency Communication

Results from a clinical study evaluating the safety and efficacy of a third booster dose of Comirnaty (Pfizer-BioNTech COVID-19 vaccine). The most common adverse reactions (ARs) reported in the phase II/III portion of the study were injection site pain (83% patients), fatigue (63.7%) and headache (48.4%). The most common unsolicited AR was lymphadenopathy (5.2%), which was severe in 1 participant. Other ARs are listed. [Data from FDA Briefing Information (COMIRNATY) for the September 17, 2021 Meeting of the FDA Vaccines and Related Biological Products Advisory Committee] Regulatory Agency Communication

The most common side effects of Brukinsa (zanubrutinib; BTK inhibitor) are neutropenia, thrombocytopenia, upper respiratory tract infection, hemorrhage, hematoma, rash, bruising, anemia, musculoskeletal pain, diarrhea, pneumonia and cough. [Data from EMA summary of opinion for Brukinsa] Regulatory Agency Communication

Protagonist Therapeutics communication announcing that the FDA has put all clinical studies of rusfertide (hepcidin mimetic) on hold after an increased risk of benign and malignant subcutaneous skin tumors was observed in a preclinical study in RasH2 transgenic mice.  Company Communication

The FDA has updated the product information of Ultram (tramadol hydrochloride; opioid mu receptor agonist), adding a warning for hyponatremia (including severe cases and cases resulting from syndrome of inappropriate antidiuretic hormone) and hypoglycemia. Regulatory Agency Communication

Exkivity carries a black box warning for life-threatening heart rate-corrected QT (QTc) prolongation, including Torsades de Pointes, which can be fatal. [Data from FDA approved drug report for Exkivity (mobocertinib; EGFR/HER2 inhibitor)] Regulatory Agency Communication

Phase II trial of vixotrigine (Nav1.7 blocker; 200/350 mg PO bid) in 265 patients with small fiber neuropathy. The most common adverse events (≥ 2.5% patients) in the open-label period were dizziness, headache, vertigo and nausea. [Data from a Biogen communication announcing positive topline results from its phase II study of vixotrigine for the treatment of small fiber neuropathy] Company Communication

The UK MHRA has issued safety advice on the risk of topical steroid withdrawal reactions. Characteristic signs include dermatitis, redness, stinging, burning and rash. 55 reports of topical steroid withdrawal reactions (including severe events) have been identified in the UK. The product information of topical corticosteroids will be updated accordingly. Regulatory Agency Communication

Phase Ib study of Aivita COVID-19 vaccine in 31 healthy Indonesian subjects. The most common adverse events were local injection site reactions and systemic flu-like symptoms such as headache, arthralgia and myalgia. [Data from an AIVITA Biomedical communication announcing positive clinical data of its COVID-19 vaccine] Company Communication

Complementary analysis of a phase IIb study of ABX464 (microRNA 124 expression enhancer; 25-100 mg) in patients with ulcerative colitis. The most frequent adverse events were headache, nausea and gastrointestinal pain. [Data from an Abivax communication updating clinical data from ABX464 for ulcerative colitis] Company Communication

The special warnings and precautions for use section of the MHRA SmPC for Cibinqo indicates that it may cause serious infections (including herpes simplex, herpes zoster and pneumonia); herpes zoster/simplex reactivation; eczema herpecticum; venous thrombosis (including pulmonary embolism and deep vein thrombosis); malignancies (including non-melanoma skin cancer); decreased absolute lymphocyte and platelet counts; and increased blood lipid parameters. [Data from MHRA Summary of Product Characteristics for Cibinqo (abrocitinib; JAK1 inhibitor)] Regulatory Agency Communication

Very common (≥1/10) adverse reactions (ADRs) reported in clinical trials with Voxzogo included hypotension, vomiting and injection site reactions (including erythema, swelling, urticaria, pain, bruising, pruritus, hemorrhage, discoloration and induration). Other very common ADRs are listed. [Data from EMA European public assessment report for Voxzogo (vosoritide; C-type natriuretic peptide analog)] Regulatory Agency Communication

Astellas communication reporting that the participant from the ASPIRO trial who suffered a serious adverse event after receiving AT132 (myotubularin gene therapy) has died. The patient was the first and only participant dosed after the release of the earlier FDA clinical hold. Company Communication

The Summary of Product Characteristics for Rinvoq (upadacitinib; JAK1 inhibitor) has been updated to reflect new safety and efficacy information following an extension of the indication. Novel adverse drug reactions including folliculitis, influenza, anemia, abdominal pain, fatigue, urticaria, headache and acne were added to the “undesirable effects” section. Regulatory Agency Communication

Conclusions from a Periodic Safety Update Report of Rydapt (midostaurin; FLT3/KIT/PKC inhibitor). Based on data from clinical trials, the literature and spontaneous reports, a causal relationship between midostaurin and the risk of interstitial lung disease, pneumonitis and electrocardiogram QT prolongation is considered at least a reasonable possibility. The product information of midostaurin-containing products will be amended accordingly. Regulatory Agency Communication