Article Archives - Page 13 of 21

Trastuzumab Deruxtecan has promising activity in Advanced Colorectal Cancer

Trastuzumab deruxtecan, an antibody-drug conjugate, showed “promising and durable activity” in HER2-positive metastatic colorectal cancer (CRC) refractory to standard treatment in an open-label phase-2 trial.

HER2 amplification is seen in 2% to 3% of colorectal tumors, but there are currently no approved HER2-targeted therapies for colorectal cancer.

The DESTINY-CRC01 trial evaluated trastuzumab deruxtecan in 78 patients with HER2-expressing metastatic CRC that had progressed on two or more previous regimens, including HER2-targeted therapies other than trastuzumab deruxtecan.

Patients were grouped by HER2-expression level: cohort A (HER2-positive, immunohistochemistry (IHC) 3+ or IHC2+ and in-situ hybridization (ISH)-positive; 53 patients); cohort B (IHC2+ and ISH-negative, seven patients); cohort C (IHC1+, 18 patients).

They received 6.4 mg/kg trastuzumab deruxtecan intravenously every three weeks until disease progression, unacceptable side effects, withdrawal of consent, or death.

After median follow up of 27 weeks, the objective response rate in cohort A (the primary endpoint) was 45.3% (24 of 53 patients). There was one (2%) complete response (2%) and 23 partial responses (43%), Dr. Salvatore Siena of the University of Milan, in Italy, and colleagues report in The Lancet Oncology.

Within cohort A, a greater proportion of patients with high levels of HER2 expression (IHC3+) had an objective response than did patients with IHC2+ and ISH-positive tumors (57.5% vs. 7.7%). “However, due to the low number of patients enrolled with IHC2+ and ISH-positive tumors, further studies are needed,” the investigators say.

“Although trastuzumab deruxtecan has shown antitumour activity in HER2-low breast tumors, no responses were seen among patients with HER2-low metastatic colorectal cancer tumors (cohort B, IHC2+ and ISH-negative; cohort C, IHC1+),” they note.

Source: Medscape

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Varenicline nasal spray trial for Dry Eye

An experimental varenicline nasal spray can reduce signs and symptoms of dry eye disease, the results of a phase 3 trial suggest. That’s because Oyster Point’s OC-01 works by stimulating the trigeminal nerve through the nasal passage, causing the eyes to tear. By contrast, most current treatments are either anti-inflammatories or artificial tears that don’t include all the components of natural ones.

OC-01 also improves symptoms relatively fast — in as few as 14 days, rather than the 3-6 months needed for some other dry eye treatments.

Source: Medscape

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DCGI gives emergency approval of DRDO-developed anti-COVID oral drug

The Institute of Nuclear Medicine and Allied Sciences (Inmas) in collaboration with Dr Reddy’s Laboratories, Hyderabad, developed an anti-COVID-19 therapeutic application of the drug 2-deoxy-D-glucose (2-DG). The third phase of the clinical trial results has shown that this molecule helps in the faster recovery of hospitalized patients and reduces supplemental oxygen dependence. A higher proportion of patients treated with 2-DG showed RT-PCR negative conversion in patients infected with the coronavirus.

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Four months TB regimen

A new drug combination containing rifapentine and moxifloxacin has finally broken the 6-month treatment barrier for drug-susceptible pulmonary tuberculosis, requiring only 4 months to produce a disease-free state at 1 year in most patients.

In open-label, phase 3, multinational trial, Doctors pitted 4-month regimens containing 1200 mg of rifapentine taken once daily with or without 400 mg of moxifloxacin taken daily against a standard 6-month regimen of rifampin, isoniazid, pyrazinamide, and ethambutol. For both 4-month treatments, rifapentine replaced rifampin, and for one of them, moxifloxacin also replaced ethambutol.

Source: The New England Journal of Medicine

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Torsemide over Furosemide as first line Loop Diuretic for HF

Three reasons why consider torsemide should be considered a first-line treatment for heart failure.

In a trial published in 2001, researchers randomized 234 patients with heart failure to receive torsemide or furosemide for 1 year. The percentage of patients who had one or more hospital readmissions was lower among those who received torsemide, compared with those who received furosemide in the torsemide group for heart failure (17% vs. 32%, respectively; P < .01) and for other cardiovascular causes (44% vs. 59%; P = .03). In addition, the number of total admissions was numerically lower for patients in the torsemide group, compared with the furosemide group for heart failure (23 vs. 61; P < .01) and for cardiovascular causes (78 vs. 130; P = .02).

In a separate study, researchers conducted an open-label trial of 237 patients with New York Heart Association (NYHA) class II-IV heart failure who were randomized to torsemide or furosemide. They found that a significantly higher percentage of patients in the torsemide group improved by one or more NYHA heart failure class, compared with those in the furosemide group (40%; P = .001 vs. 31%; P = .3). Moreover, patients treated with furosemide had more restrictions of daily life at 9 months, compared with those treated with torsemide (P < .001).

A separate, open-label, nonrandomized, postmarketing surveillance trial also found benefits of torsemide over furosemide or other agents used for patients with NYHA class III and IV heart failure. Patients treated with torsemide had a lower total mortality, compared with those treated with furosemide or other agents (2.2% vs. 4.5%, respectively; P < .05) as well as a lower cardiac mortality (1.4% vs. 3.5%; P < .05). They were also more likely to improve by one or more heart failure class (46% vs. 37%; P < .01) and less likely to have potassium levels less than 3.5 mEq/L or greater than 5.0 mEq/L (13% vs. 18%; P = .01).

Source: Medscape

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New oral protein shows promise for Ulcerative Colitis

A plant-based fusion protein is safe and effective for inducing favorable immune modulation in patients with mild to moderate ulcerative colitis with no immune suppression–side effects reported.

OPRX-106, an orally administered BY2 plant cell–expressing recombinant TNF fusion protein, has demonstrated effectiveness as an anti–TNF-alpha therapy.

After 8 weeks, 67% of the patients demonstrated clinical response and 28% showed clinical remission. 89% of the patients experienced some degree of improvement in their Mayo scores, 61% had mucosal improvement, and 33% achieved mucosal healing.

Source: Medscape

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ECMO support in COVID-19 patients with refractory ARDS

COVID-19 patients treated with extracorporeal membrane oxygenation (ECMO) appear to have a much lower mortality rate than initial early reports suggested.

ECMO has been utilized in COVID-19 patients with acute respiratory distress syndrome (ARDS) and hypoxemia that fails to respond to standard treatment. But early case series suggested a high mortality rate – topping 90%.

The in-hospital mortality rate was 45.9%, far lower than initial early reports and refuting previous reports of futility for ECMO in COVID-19 patients with ARDS.

Source: Reuters

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FDA approves Dapagliflozin for Chronic Kidney Disease

The US Food and Drug Administration (FDA) has approved dapagliflozin (Farxiga, AstraZeneca) to reduce the risk for kidney function decline, kidney failure, cardiovascular death, and hospitalization for heart failure in adult patients with chronic kidney disease (CKD) at risk for disease progression.

Dapagliflozin (5mg, 10mg OD) is a selective sodium-glucose transporter-2 (SGLT2) inhibitor.

Uses:

Type 2 Diabetes Mellitus: Initial 5 mg PO qDay in AM
Reduce the risk of hospitalization for heart failure: 10 mg PO qDay in AM. Used in Heart Failure with a reduced ejection fraction
Chronic Kidney Disease: Indicated to reduce risk of sustained eGFR decline, end-stage kidney disease (ESKD), cardiovascular death, and hospitalization for HF in adults with CKD who are at risk of progression

Dosage Modifications:
1. Renal impairment
eGFR ≥45mL/min/1.73 m2: No dosage adjustment required

2. eGFR 25 to <45 mL/min/1.73 m2
T2DM: Not recommended
3. HF or CKD: No dosage adjustment required
4. eGFR <25 mL/min/1.73 m2
Initiation not recommended
5. Patients with HF or CKD may continue 10 mg/day to reduce risk of eGFR decline, ESKD, CV death, and HF hospitalization
6. ESRD/dialysis: Contraindicated

7. Hepatic impairment
Mild or moderate: No dosage adjustment required
Severe: Not studied
Dosing Considerations

Source: FDA

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Tralokinumab gets nod for Atopic Dermatitis in Europe

European Medicines Agency (EMA) issued a positive opinion for the IL-13 inhibitor tralokinumab (Adtralza) for the treatment of adults with moderate-to-severe atopic dermatitis (AD) who are eligible for systemic therapy.

Tralokinumab would become the first approved fully human monoclonal antibody targeting the IL-13 cytokine, a key factor that drives the signs and symptoms of AD. Tralokinumab has previously shown to target IL-13 with high affinity and subsequently improve symptoms associated with inflammatory skin disease.

The US Food and Drug Administration accepted a Biologics License Application for tralokinumab for the treatment of moderate-to-severe AD in adults. Data from the pivotal ECZTRA 1, 2 and ECZTRA 3 phase 3 studies were also submitted to the FDA alongside the BLA.

Source: Medscape

Clinic Hours In Article, COVID-19

DCGI approves Virafin, Pegylated Interferon alpha-2b for COVID-19

Zydus Cadila announced that it has received restricted emergency use approval from the Indian drug regulator, Drug Controller General of India (DCGI), for the use of ‘Virafin’, Pegylated Interferon alpha-2b (PegIFN) in treating moderate coronavirus infection in adults.

In its Phase-3 clinical trials, a single dose subcutaneous regimen of the antiviral Virafin had shown better clinical improvement in the COVID-19 patients. “During the trials, a higher proportion of patients administered with PegIF were RT PCR negative by day 7. The drug ensures faster viral clearance and has several add-on advantages compared to other anti-viral agents,” the company said.

Pegylated Interferon alpha-2b was originally approved for Hepatitis C.

Source: Zydus Cadila