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Phase II study of paxalisib (mTOR/PI3K inhibitor; up to 60 mg qd) in 30 patients with newly diagnosed glioblastoma. The most common paxalisib-related toxicities were hyperglycemia, oral mucositis and skin rash. [Data from a Kazia communication announcing positive final data from a phase II trial of paxalisib] Company Communication

First-in-human phase I/II trial of TAK-981 (SUMO inhibitor; 3-40 mg IV biw or 60-120 mg IV qwk/biw) in 76 patients with advanced/metastatic solid tumors or relapsed/refractory lymphomas. The most common treatment-emergent adverse events (TEAEs) were fatigue (42.1% patients), nausea (39.5%), headache (31.6%), diarrhea (28.9%), pyrexia (27.6%), vomiting (23.7%) and decreased appetite (22.4%). Common grade ≥3 TEAEs included hypokalemia (9.2%), anemia (7.9%), lymphocyte count decrease (6.6%) and abdominal pain (5.3%). 4 patients experienced grade 2 cytokine release syndrome. Grade 3 dose-limiting toxicities included ALT/AST elevation, pneumonitis, stomatitis and cognitive disturbance. Congress Alert

Phase Ia/Ib study evaluating single and multiple doses of AB-836 (viral core protein inhibitor; 10-175 mg PO) in healthy subjects and patients with chronic hepatitis B virus (cHBV) infection. 1 healthy subject developed a grade 1 rash considered related to AB-836. 1 patient with cHBV infection receiving AB-836 at 100 mg exhibited a grade 3 increase in ALT. [Data from an Arbutus Biopharma communication announcing preliminary data from an ongoing trial of AB-836 in healthy subjects and patients with cHBV infection] Company Communication

New Zealand’s Medsafe has issued a communication alerting about the risk of thromboembolic events associated with omalizumab (Ig epsilon chain C region inhibitor). In clinical studies, patients receiving omalizumab showed higher rates of arterial thromboembolic events (including stroke, transient ischemic attack, myocardial infarction, unstable angina and cardiovascular death) than control patients. Regulatory Agency Communication

New Zealand’s Medsafe has issued a list of medicines that can cause taste disturbances, including terbinafine, atorvastatin, metoprolol succinate, omeprazole, varenicline and zopiclone. Regulatory Agency Communication

Phase I study of CoVepiT (SARS-CoV-2 proteins-directed immunity inducer) in healthy volunteers. Nodule-like indurations at the injection site were observed during the vaccination. [Data from an OSE Immunotherapeutics communication announcing positive data of its COVID-19 vaccine CoVepiT] Company Communication

The special warnings and precautions for use section of the EMA EPAR for Vumerity indicates that it may cause lymphopenia; progressive multifocal leukoencephalopathy; flushing; herpes zoster infections; and gastrointestinal adverse reactions. Cases of anaphylaxis/anaphylactoid reactions such as dyspnea, hypoxia, hypotension, angioedema, rash and urticaria have been reported in the postmarketing setting with dimethyl fumarate. Other adverse events that may occur with Vumerity, dimethyl fumarate or natalizumab are listed. [Data from EMA European public assessment report for Vumerity (diroximel fumarate; kelch-like ECH-associated protein 1/NF-kappaB inhibitor)] Regulatory Agency Communication

Results from non-clinical studies evaluating the risk of mutagenicity, embryo-fetal toxicity, and bone and cartilage development disorders associated with molnupiravir (viral RNA polymerase inhibitor). Safety issues are listed. [Data from FDA Briefing Information (molnupiravir) for the November 30, 2021 Meeting of the Antimicrobial Drugs Advisory Committee] Regulatory Agency Communication

The special warnings and precautions for use section of the EMA EPAR for Trodelvy indicates that it may cause severe neutropenia; severe diarrhea; severe hypersensitivity and anaphylactic reactions; nausea and vomiting; embryo-fetal toxicity, teratogenicity and embryo-fetal lethality (based on the payload's mechanism of action); and genotoxicity. Patients who are homozygous for the UGT1A1*28 allele have an increased risk for neutropenia, febrile neutropenia and anemia when exposed to sacituzumab govitecan. [Data from EMA European public assessment report for Trodelvy (sacituzumab govitecan; DNA topoisomerase 1/tumor-associated calcium signal transducer 2 inhibitor)] Regulatory Agency Communication

The FDA has updated the product information of Inrebic (fedratinib hydrochloride; JAK2 inhibitor), adding warnings for major adverse cardiac events including cardiovascular death, myocardial infarction and stroke; thrombosis including deep venous thrombosis, pulmonary embolism and arterial thrombosis; and secondary malignancies including lymphoma and other malignancies (excluding non-melanoma skin cancer). This follows the results from a study concluding that these adverse reactions occurred more frequently with a JAK inhibitor than with TNF-alpha inhibitors in patients with rheumatoid arthritis, a condition for which Inrebic is not indicated. Regulatory Agency Communication

The warnings and precautions section of the FDA approved drug report for Cytalux indicates that it may cause infusion-related reactions (including nausea, vomiting, abdominal pain, flushing, dyspepsia, chest discomfort, and pruritus); and hold risks of misinterpretation during intraoperative fluorescence imaging to detect ovarian cancer (including detection of false negatives and false positives). When used with an incorrect diluent, aggregation potentially leading to infusion-related reactions (including nausea, vomiting, abdominal pain, and rash) may take place. Based on its mechanism of action, Cytalux may cause embryo-fetal toxicities (including fetal harm) when administered to pregnant women. [Data from FDA approved drug report for Cytalux (pafolacianine; folate receptor ligand)] Regulatory Agency Communication

Conclusions from a Periodic Safety Update Report on lanthanum (phosphate sequestrant). Cases of lanthanum deposition in the gastroduodenal mucosa have been reported. Various pathological features associated with lanthanum deposition have been identified, including lesions of different sizes and shapes in the mucosa, chronic or active inflammation, glandular atrophy, foveolar hyperplasia and intestinal metaplasia and neoplasia. The product information of products containing lanthanum will be updated accordingly. Regulatory Agency Communication

Conclusions from a Periodic Safety Update Report on Lyrica (pregabalin; voltage-dependent calcium channel subunit alpha-2/delta-1 ligand). The PRAC considers that a causal relationship between pregabalin and parkinsonism is established. The product information of products containing pregabalin should be updated accordingly. Regulatory Agency Communication

The special warnings and precautions for use section of the EMA EPAR for Qinlock indicates that it may cause palmar-plantar erythrodysesthesia syndrome; hypertension; cardiac failure including acute cardiac failure, acute left ventricular failure and diastolic dysfunction; cutaneous squamous cell carcinoma; embryo-fetal toxicity based on findings from animal studies; and phototoxicity. As ripretinib inhibits VEGF signaling pathway, it has the potential to adversely affect wound healing. Drug-drug interactions of ripretinib with itraconazole and rifampicin have been reported. [Data from EMA European public assessment report for Qinlock (ripretinib; KIT/PDGFRalpha inhibitor)] Regulatory Agency Communication

Interim results from a first-in-human phase I study of belcesiran (alpha-1-antitrypsin expression inhibitor; 0.1-12 mg/kg SC) in 30 healthy volunteers. 4 participants (13.3%) experienced protocol defined injection-site reactions. Congress Alert

Phase IIb dose-ranging study of vupanorsen (angiopoietin like 3 expression inhibitor; 60-160 mg SC q2w or q4w) in 286 adults with dyslipidemia. The most common adverse events were injection-site reactions, occurring more frequently in patients receiving the highest dose. The most common laboratory abnormalities were increases in liver enzymes (ALT and AST), which were also mainly reported at higher doses. Certain doses of vupanorsen were also associated with increased hepatic fat fraction. [Data from a Ionis Pharmaceuticals communication announcing that Pfizer has provided topline results from the TRANSLATE-TIMI 70 trial] Company Communication

The most common side effects reported in children (aged 5 to 11) receiving Comirnaty (Pfizer-BioNTech COVID-19 vaccine) were tiredness, headache, muscle pain, chills, and injection-site pain, redness and swelling. [Data from an EMA press release announcing the extension of indication for the use of Comirnaty in children aged 5 to 11] Regulatory Agency Communication

Conclusions from a Periodic Safety Update Report on Triumeq (abacavir sulfate/dolutegravir sodium/lamivudine). The PRAC considers that a causal relationship between dolutegravir and panic attack is at least a reasonable possibility. The “Undesirable effects” section of products containing dolutegravir will be updated to include panic attack with a frequency “uncommon”. Regulatory Agency Communication

The PMDA is currently reviewing the association between fingolimod hydrochloride (S1P1/5 receptor agonist) and the risk of thrombocytopenia. Regulatory Agency Communication