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The warnings and precautions section of the FDA approved drug report for Saphnelo indicates that it may cause serious and sometimes fatal infections, including respiratory infections and herpes zoster; and serious hypersensitivity reactions, including anaphylaxis and other infusion-related reactions. Although the impact of Saphnelo on the potential development of maligancies is not known, there is an increased risk with the use of immunosuppressants. [Data from FDA approved drug report for Saphnelo (anifrolumab-fnia; interferon alpha/beta receptor 1 antagonist)] Regulatory Agency Communication

Phase IV immunogenicity and safety study of CoronaVac (Sinovac COVID-19 vaccine) in patients with autoimmune rheumatic disease (ARD) and matched healthy subjects. The most common adverse events (AEs) were injection-site pain (180/909 [19.8%] patients with ARD vs 31/182 [17%] healthy controls), headache (184 [20.2%] vs 20 [11%]), somnolence (124 [13.6%] vs 19 [10.4%]) and arthralgia (123 [13.5%] vs 11 [6%]) after the first vaccine dose. Other AEs reported after the first and the second dose are listed.

Phase III study of lumasiran (hydroxyacid oxidase 1 expression inhibitor) in 21 patients with advanced primary hyperoxaluria type 1. The most frequent drug-related adverse event was injection site reaction (5 patients [23.8%]). [Data from an Alnylam communication announcing positive results from the ILLUMINATE-C study] Company Communication

Retrospective disproportionality analysis evaluating the association between antidepressants and hypertension using data from the French pharmacovigilance database. Hypertension was significantly associated with serotonin/norepinephrine reuptake inhibitors (SNRIs; ROR = 1.43 [1.26-1.64]) and with monoamine oxidase inhibitors (MAOIs; 6.41 [4.25-9.67]). SNRIs significantly associated with hypertension were duloxetine, milnacipran and venlafaxine, while MAOIs significantly associated with this adverse event were moclobemide and iproniazid. Celecoxib was used as a positive control.

The warnings and precautions section of the FDA emergency use authorization prescribing information for baricitinib indicates that it may cause serious infections. [Data from FDA Emergency Use Authorization Prescribing Information for baricitinib (JAK1/2 inhibitor)] Regulatory Agency Communication

First-in-human study of CX-072 (pacmilimab; PD-L1 inhibitor; 0.3-10 mg/kg IV q2w) in patients with advanced solid tumors. The most common treatment-related adverse events (TRAEs) were fatigue (18 [16%] patients; 1 [1%] grade 3), AST increase (15 [13%]; 1 [1%]), ALT increase (12 [11%]), infusion-related reaction and rash (9 [8%] each). Immune-related adverse events (irAEs) included hypothyroidism (5 [4%]), rash (3 [3%]), acute thyroiditis and myocarditis (1 [1%] each). Other TRAEs and irAEs are listed.

First-in-human phase Ib study of ATRC-101 (0.3-30 mg/kg IV q21d) in 24 patients with advanced solid tumors. The most common treatment-related adverse events (TRAEs) were fatigue (5 patients [20.8%]), nausea, tumor pain (4 [16.7%] each), pain (3 [12.5%]), blood alkaline phosphatase increase, chills, decreased appetite, dyspnea, gastritis and pyrexia (2 [8.3%] each). 1 patient developed a grade ≥3 TRAE of small intestinal obstruction. Other AEs are listed. [Data from an Atreca presentation on ATRC-101] Company Communication

The special warnings and precautions for use section of the EMA EPAR for Bylvay indicates that it may cause diarrhea leading to dehydration; and increased liver function tests. Bylvay may alter the absorption of fat-soluble medicinal products, including lipophilic oral contraceptives. [Data from EMA European public assessment report for Bylvay (odevixibat; ASBT inhibitor)] Regulatory Agency Communication

Phase I first-in-human study of CX-072 (pacmilimab; PD-L1 inhibitor; 0.3-10 mg/kg IV q3w) in combination with ipilimumab (CTLA-4 inhibitor; 3 or 6 mg/kg IV q3w) in 27 patients with advanced solid tumors. Treatment-related adverse events (AEs) included pruritus (10 patients [37%]), nausea (9 [33%]), increased AST (6 [22%]; 1 [4%] grade 3-4), fatigue (5 [19%]) and increased ALT (5 [19%]; 1 [4%]). 3 patients reported grade 3 dose-limiting toxicities: dyspnea/pneumonitis, colitis and increased AST (1 each). 16 patients (59%) reported immune-related AEs (6 [22%] grade 3-4). Other AEs are listed.

The FDA is requiring suspend enrollment in all ongoing clinical studies of Pepaxto (melphalan flufenamide; DNA alkylating agent) after reporting an increased risk of death in patients receiving Pepaxto plus dexamethasone in the OCEAN trial. Regulatory Agency Communication

The warnings and precautions section of the FDA approved drug report for Twyneo indicates that it may cause skin irritation including application site dryness, pain, exfoliation, erythema, dermatitis, pruritis and irritation; and photosensitivity. Benzoyl peroxide products may cause hypersensitivity reactions including anaphylaxis, angioedema and urticaria. [Data from FDA approved drug report for Twyneo (benzoyl peroxide/tretinoin)] Regulatory Agency Communication

Conclusions from a Periodic Safety Update Report of Aubagio (teriflunomide; DHODH inhibitor). The PRAC has recommended updating the product information to include the risk of colitis and pulmonary hypertension. A causal relationship between Aubagio and these events is considered at least a reasonable possibility. Regulatory Agency Communication

Clinical study of eganelisib (PI3Kgamma inhibitor; 30 mg qd) combined with atezolizumab (PD-L1 inhibitor) and nab-paclitaxel (microtubule stabilizing agent) in 60 patients with metastatic triple-negative breast cancer. Eganelisib-related treatment-emergent adverse events (≥25% patients) were fatigue (17 [39.5%] patients; 1 [2.3%] grade ≥3), nausea (14 [32.6%]), maculopapular rash (11 [25.6%]; 4 [9.3%]), diarrhea (11 [25.6%]; 1 [2.3%]), aspartate aminotransferase increase (9 [23.3%]; 6 [14%]), alanine aminotransferase increase (9 [20.9%]; 8 [18.6%]) and alopecia (3 [7%]). [Data from an Infinity Pharmaceuticals presentation on eganelisib] Company Communication

The FDA has updated the product information of Drizalma sprinkle (duloxetine hydrochloride; SERT/NET inhibitor), adding a warning about sexual dysfunction (including ejaculation delay or failure, decreased libido and erectile dysfunction in male patients; and decreased libido and delayed/absent orgasm in women). Sexual dysfunction is a class effect of SERT/NET inhibitors. Regulatory Agency Communication

First-in-human phase I study of SGN-2FF (fucosyltransferase 3 inhibitor; 1-15 g qd or 2-5 g bid) followed by combined SGN-2FF/pembrolizumab in 32 patients with advanced solid tumors. The most common treatment-emergent adverse events (AEs; ≥20% patients) were diarrhea, fatigue and nausea during the monotherapy part; and decreased appetite, fatigue and back pain during the combination part. Drug-related AEs leading to SGN-2FF monotherapy discontinuation included increased lipase and fatal hyponatremia (1 patient each). Other AEs are listed.

The FDA has updated the product information of Keytruda (pembrolizumab; PD-1 inhibitor) to include novel safety data from a phase III study evaluating lenvatinib plus pembrolizumab in patients with endometrial carcinoma. Novel adverse reactions are listed. Regulatory Agency Communication

Results from 2 phase I/II studies of zanubrutinib (BTK inhibitor) in 118 patients with mantle cell lymphoma. 3.4% patients discontinued zanubrutinib due to pneumonia. Adverse events resulting in dose reductions included hepatitis B, neutropenia, allergic dermatitis and peripheral sensory neuropathy (1 patient each). [Data from a BeiGene communication announcing that Health Canada has approved Brukinsa for the treatment of mantle cell lymphoma] Company Communication

Adverum Biotechnologies has discontinued the development program of ADVM-022 (placenta growth factor/VEGF inhibitor) for diabetic macular edema after an unexpected dose-limiting toxicity of hypotony was reported in a phase II trial. Several patients treated with a single high dose of ADVM-022 (6E11 vg/eye) experienced decreases in intraocular pressure. Company Communication

First-in-human phase I study of ANX009 (complement C1q inhibitor) in healthy subjects. Some participants developed mild injection site reactions after subcutaneous administration of ANX009. [Data from an Annexon communication announcing a broadening of its autoimmune franchise] Company Communication

The special warnings and precautions for use section of the EMA EPAR for Imcivree indicates that it may cause generalized skin hyperpigmentation and darkening of pre-existing nevi by stimulating MC1 receptors; spontaneous penile erections (considered an on-target effect); depression; and weight loss in pediatric population. The excipient benzyl alcohol may cause allergic reactions and metabolic acidosis. [Data from EMA European public assessment report for Imcivree (setmelanotide; MC4 receptor agonist)] Regulatory Agency Communication

The most common side effects of Nexviadyme (avalglucosidase alfa; lysosomal alpha-glucosidase analog) are hypersensitivity (including anaphylaxis) and infusion-associated reactions such as pruritus, rash, headache, urticaria, fatigue, nausea and chills. [Data from EMA summary of opinion for Nexviadyme] Regulatory Agency Communication