FDA Updates

The USA FDA has approved Aprocitentan (Brand name TRYVIO) for the treatment of resistant hypertension in combination with other antihypertensive drugs.

Dose: 12.5 mg 1OD PO.

MOA: Dual endothelin receptor antagonist.

Contraindications: Pregnancy, Hypersensitivity.

Adverse effects: Edema, anemia, ⬇️ sperm count.

Warning & precautions: ERAs cause hepatotoxicity & liver failure.

Trial: PRECISION was a multicentre, blinded, randomised, parallel-group, phase 3 studydone in Europe, North America, Asia &  Australia in June 18, 2018, to April 25, 2022 by Prof Markus P Schlaich, MD et al.

Inclusion criteria: Patients with SBP > 140 mmhg who were on 3 different anti hypertensive medications including diuretics.

Objectives: The primary endpoints were changes in SBP from baseline to 4 week & from withdrawal baseline to 40 week. Secondary endpoints included 24-h ambulatory blood pressure changes.

Methods: Study consisted of 3 sequential parts:

Part 1 was 4-week double-blind, randomised, & placebo-controlled part, in which patients received aprocitentan 12·5 mg, 25 mg, or placebo in a 1:1:1 ratio.

Part 2 was a 32-week single patient blind part, in which all patients received aprocitentan 25 mg.

Part 3 was a 12-week double-blind, randomised, placebo-controlled withdrawal part, in which patients were re-randomised to aprocitentan 25 mg or placebo in a 1:1 ratio.

Findings: In patients with resistant hypertension, aprocitentan was well tolerated & superior to placebo in lowering blood pressure at 4 week with a sustained effect at 40 week.

Reference: http://clinicaltrials.gov/show/NCT03541174

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Sotagliflozin, a novel agent that inhibits sodium-glucose co transporter SGLT 1 & SGLT2 both as a treatment for adults with heart failure with or without diabetes and for T1DM & T2DM.

Dose: 200mg/400mg 1 OD.

MOA: Inhibiting SGLT2 reduces renal reabsorption of glucose and sodium which may influence several physiological functions, such as lowering both pre-and afterload of the heart and downregulating sympathetic activity. Inhibiting SGLT1 reduces intestinal absorption of glucose and sodium which likely contributes to diarrhea.

Adverse Effects:  >10% UTI, Diarrhea, Hypoglycemia, Dizziness, Genital mycotic infection.

Other approved drugs are SGLT2 inhibitors empagliflozin & dapagliflozin , both of which now have labeled indications across the spectrum of LVEF.

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The US FDA has approved extended-release injection buprenorphine (Brixadi, Braeburn Inc) for the treatment of moderate to severe opioid use disorder (OUD). The medication comes in two formulations: a weekly and a monthly version. The  adverse reactions include headache, constipation, nausea, injection-site erythema, injection-site pruritus, insomnia & UTI.

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The US FDA has approved dabrafenib with trametinib for children aged 1 year or older who need systemic treatment for low-grade gliomas that have a BRAF V600E mutation. Dabrafenib/trametinib is the first systemic therapy approved for frontline treatment of low-grade, BRAF-mutated pediatric gliomas, the FDA said. Dabrafenib was given orally twice daily, and trametinib was given orally once daily. Children in the chemotherapy arm received a 10-week induction course followed by eight 6-week maintenance cycles.

Adverse effects: pyrexia (66%), rash (54%), headache (40%), vomiting (38%), musculoskeletal pain (36%), fatigue (31%), dry skin (31%), diarrhea (30%), nausea (26%), epistaxis and other bleeding events (25%), abdominal pain (24%), and dermatitis acneiform (23%). The more common grade 3 or 4 laboratory abnormalities were decreased neutrophil count (20%) and increases in alanine aminotransferase (3.1%) and aspartate aminotransferase levels (3.1%).

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The US FDA has approved efanesoctocog alfa (Altuviiio), a first-in-class, high-sustained factor VIII replacement therapy for adults and children with hemophilia A. The product is used once a week and is indicated for routine prophylaxis and on-demand treatment to control bleeding episodes, as well as to control bleeding during surgery (perioperative management).

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The US FDA approved a new indication for sacituzumab govitecan for patients with unresectable, locally advanced or metastatic hormone receptor (HR)-positive, HER2-negative breast cancer after endocrine-based therapy and at least two additional systemic therapies for metastatic disease.

Adverse events: decreased leukocyte count, decreased neutrophil count, decreased hemoglobin, decreased lymphocyte count, diarrhea, fatigue, nausea, alopecia, glucose elevation, constipation, and decreased albumin. Labeling for the agent carries a black box warning of severe or life-threatening neutropenia and severe diarrhea.

Dose: 10 mg/kg IV on days 1 and 8 of 21-day cycles until disease progression or unacceptable toxicity.

Sacituzumab govitecan was previously approved for unresectable, locally advanced or metastatic triple-negative breast cancer after two or more prior systemic therapies and locally advanced or metastatic urothelial cancer after platinum-based chemotherapy and either a PD-1 or PD-L1 inhibitor.

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The US FDA approved pirtobrutinib (Jaypirca) for relapsed or refractory mantle cell lymphoma (MCL) after at least two lines of systemic therapy, including a Bruton’s tyrosine kinase (BTK) inhibitor. Pirtobrutinib is the first and only non-covalent BTK inhibitor.

Dose: 200 mg once-daily

Adverse reactions: Fatigue, musculoskeletal pain, diarrhea, edema, dyspnea, pneumonia, bruising, decreased neutrophil counts, lymphocyte counts, and platelet counts.

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The US FDA has approved mosunetuzumab-axgb (Lunsumio) for use in patients with relapsed or refractory follicular lymphoma who have received at least two previous systemic therapies. This is a first-in-class bispecific antibody that is designed to target CD20 on the surface of B cells and CD3 on the surface of T cells. This dual targeting activates and redirects a patient’s existing T cells to engage and eliminate target B cells by releasing cytotoxic proteins into the B cells. Mosunetuzumab-axgb is administered as an intravenous infusion for a fixed duration, which allows for time off therapy, and can be infused in OPD.

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