DIABETES
Novel drug reaches glycemic, weight targets faster
Tirzepatide (MOUNJARO, Eli Lilly) (TZP), a novel dual glucose-dependent insulinotropic polypeptide receptor and glucagon-like peptide-1 (GLP-1) receptor agonist, helped patients with type 2 diabetes reach glycemic targets faster than the GLP-1 receptor agonist semaglutide (SEMA) 1 mg and the long-acting human insulin analogue, titrated insulin degludec (iDeg), according to an abstract published at the 2022 European Association for the Study of Diabetes.
Results were derived from the trials SURPASS-2 and 3. TZP was initiated at 2.5 mg once daily and increased by 2.5 mg every 4 weeks until the assigned dose was reached and maintained for the duration of the study. SEMA was initiated at 0.25 mg once weekly, and the dose doubled every 4 weeks until 1 mg was reached and maintained for the duration of the study. iDeg was initiated at 10 units/day and titrated weekly to fasting blood glucose of less than 5.0 mmol/L following a treat-to-target algorithm.
In an exploratory, preplanned analysis, the time to achieve glycemic targets was estimated using the Kaplan Meier method and the hazard ratio between treatments was calculated using a cox proportional-hazards model.
Overall, TZP was significantly faster than SEMA and iDeg in time to reach an A1C less than 53 mmol/mol (7%) and less than or equal to 48 mmol/mol (6.5%). The median time to achieve an A1C less than 53 mmol/mol (7%) was 8.1 weeks for all TZP doses and 12.0 weeks for SEMA doses. The time to reach an A1C less than or equal to 48 mmol/mol (6.5%) was 12.1 weeks for TZP and 15.7 weeks for SEMA. The time to lose 5% body weight was an average of 13.6 weeks across all TZP dosages and 24 weeks for SEMA. The median time to reach an A1C less than 53 mmol/mol (7%) was 8.1 weeks for all TZP doses and 12.1 weeks for all iDeg doses. Lastly, the time to reach an A1C less than or equal to 48 mmol/mol (6.5%) was 12.1 weeks for TZP and 24.1 weeks for iDeg.
Adverse events reported throughout the trials included mild to moderate gastrointestinal events associated with TZP, including nausea, vomiting, and diarrhea. They primarily occurred during the escalation period.
Reference: Abstracts: 58th EASD Annual Meeting of the European Association for the Study of Diabetes. 2022.
BILE DUCT CANCER
New drug approved for cholangiocarcinoma
The FDA has granted accelerated approval to futibatinib (LYTGOBI, Taiho Oncology, Inc.), a kinase inhibitor for adult patients with previously treated, unresectable, locally advanced or metastatic intrahepatic cholangiocarcinoma harboring fibroblast growth factor receptor 2 (FGFR2) gene fusions or other rearrangements.1
The approval was based on initial efficacy results from TAS-120-101 (NCT02052778), submitted to the FDA via its Real-Time Oncology Review program. As of this writing, the database for the clinical trial at http://ClinicalTrials.gov has not been updated.2
According to the FDA's press release, 103 patients with previously treated, unresectable, locally advanced, or metastatic intrahepatic cholangiocarcinoma harboring an FGFR2 gene fusion or other rearrangement participated in the trial. They received 20 mg of futibatinib orally once daily until disease progression or unacceptable toxicity. All 43 patients who responded to treatment had partial responses for a median duration of 9.7 months.
Futibatinib is available in 4 mg tablets.3 It does not carry any contraindications. Warnings and precautions issued with the use of futibatinib include possible retinal pigment epithelial detachment, hyperphosphatemia and soft tissue mineralization, and embryo-fetal toxicity.
Adverse reactions reported throughout the trial include nail toxicity, musculoskeletal pain, constipation, diarrhea, fatigue, dry mouth, alopecia, stomatitis, abdominal pain, dry skin, arthralgia, dysgeusia, dry eye, nausea, decreased appetite, urinary tract infection, palmar-plantar erythrodysesthesia syndrome, and vomiting.
References: 1. Center for Drug Evaluation and Research. FDA grants accelerated approval to futibatinib for cholangiocarcinoma. U.S. Food and Drug Administration. 2022. http://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-acceler. Accessed October 10, 2022.
2. A study of TAS-120 in patients with advanced solid tumors - full text view. http://ClinicalTrials.gov. https://clinicaltrials.gov/ct2/show/NCT02052778?term=TAS-120-101&draw=2&rank=1. Accessed October 10, 2022.
3. LYTGOBI(R) (futibatinib) Prescribing Information. 2022.
RENAL FUNCTION
New drug improves renal function in patients with HRS
The FDA has approved terlipressin (TERLIVAZ, Mallinckrodt Pharmaceuticals), a vasopressin receptor agonist indicated to improve kidney function in adults with hepatorenal syndrome (HRS) with a rapid reduction in kidney function.1
The approval is based on the results of a double-blind study. Out of 300 participants, 199 were given terlipressin and 101 were given a placebo.2 The primary outcome for the study was the percentage of participants with kidney function improvement, defined as 2 consecutive serum creatinine levels less than or equal to 1.5 mg/dL at least 2 hours apart, while on treatment by Day 14 or discharge from the study. About 29% in the terlipressin group achieved this outcome, while about 16% achieved this outcome in the placebo group.
A boxed warning issued in terlipressin's prescribing information warns of serious or fatal respiratory failure associated with its use.3 Patients with volume overload or with acute-on-chronic liver failure Grade 3 are at increased risk for respiratory failure with the use of terlipressin. Oxygen saturation should be assessed before the drug's use. Furthermore, the boxed warning says terlipressin should not be used in patients experiencing hypoxia until their oxygen levels improve. Such patients should be monitored for hypoxia via continuous pulse oximetry during treatment and the treatment should be discontinued if oxygen saturation decreases below 90%.
Terlipressin is contraindicated in patients experiencing hypoxia or worsening respiratory symptoms and those with ongoing coronary, peripheral, or mesenteric ischemia. Other warnings and precautions include ineligibility for a liver transplant, ischemic events, and embryo-fetal toxicity.
Adverse reactions reported with the use of terlipressin include abdominal pain, nausea, respiratory failure, diarrhea, and dyspnea.
References: 1. Center for Drug Evaluation and Research. FDA approves treatment to improve kidney function in adults. U.S. Food and Drug Administration. http://www.fda.gov/drugs/news-events-human-drugs/fda-approves-treatment-improve-. Accessed October 10, 2022.
2. Study to confirm efficacy and safety of terlipressin in hepatorenal syndrome (HRS) type 1 - study results. Study Results - http://ClinicalTrials.gov. https://www.clinicaltrials.gov/ct2/show/results/NCT02770716. Accessed October 10, 2022.
3. TERLIVAZ Prescribing Information.
LOU GEHRIG DISEASE
New drug approved for ALS
The FDA has approved combination therapy sodium phenylbutyrate and taurursodiol (RELYVRIO, Amylyx Pharmaceuticals) for the treatment of amyotrophic lateral sclerosis (ALS) in adults.1
Patients who received the drug in a 24-week, multicenter, randomized, double-blind, placebo-controlled, parallel-group study experienced a slower rate of decline on a clinical assessment of daily functioning than those who received the placebo.
The therapy is an oral suspension consisting of 3 g sodium phenylbutyrate and 1 g taurursodiol in single-dose packets.4 One packet may be administered orally or via a feeding tube. The initial starting dose would be one packet daily for the first 3 weeks, followed by a maintenance dose of one packet twice daily. The contents of one packet may be emptied into a cup of 8 oz of room-temperature water and stirred vigorously before administration. The contents should be taken within 1 hour of preparation and before a snack or meal.
If used in patients with enterohepatic circulation, pancreatic, or intestinal disorders, the prescribing information suggests considering consulting a specialist and monitoring for worsening diarrhea. For patients sensitive to high sodium intake, consider the amount of their sodium intake in each dose administered and monitor them appropriately.
Adverse reactions reported with the use of sodium phenylbutyrate and taurursodiol include diarrhea, abdominal pain, nausea, and upper respiratory tract infection.
References:
1. U.S. Food and Drug Administration. FDA approves new treatment option for patients with ALS. 2022. http://www.fda.gov/news-events/press-announcements/fda-approves-new-treatment-op. Accessed October 10, 2022.
2. RELYVRIO Prescribing Information.
STROKE
Fibrinolytic agent improves outcomes, decreases costs
Switching patients who have had strokes to tenecteplase (TNKase, Genentech) from alteplase can improve patient outcomes and decrease healthcare costs, according to a study published in Stroke.1
Tenecteplase is a single-bolus fibrinolytic agent approved by the FDA to reduce mortality associated with acute myocardial infarction.2
Researchers conducted a prospective registry-based observational, sequential cohort comparison of patients who had experienced a stroke and were prescribed tenecteplase (234) or alteplase (354). Total hospital costs associated with each drug were also compared.
Tenecteplase was superior in reducing door-to-needle time within 45 minutes and door-in-door-out within 90 minutes. The favorable outcome for tenecteplase fell within the 6.5% noninferiority margin; the unfavorable outcome was less for tenecteplase (7.3% versus 11.9%) but did not fall within the prespecified 1% noninferior boundary. The net benefit for tenecteplase was superior (37% versus 27%).
Regarding costs per healthcare encounter, tenectplase resulted in lower costs: $13,382 versus $15,841.
The researchers write that evaluations in larger, multicenter cohorts should be completed to see if similar results occur in those settings.
References: 1. Warach SJ, Dula AN, Milling TJ, et al. Prospective observational cohort study of tenecteplase versus alteplase in routine clinical practice. Stroke. [e-pub Sep. 23, 2022]
2. TNKASE(R) Acute Myocardial Infarction Treatment. tnkase. http://www.tnkase.com/?cid=gne_WE_00000083. Accessed October 7, 2022.