IMMUNOLOGY
Experimental EBV vaccine
The National Institutes of Health is testing an investigational preventive vaccine for Epstein-Barr virus (EBV).
The vaccine is comprised of a glycoprotein (gp)350-Ferritin nanoparticle vaccine with a saponin-based Matrix-M adjuvant. The vaccine is developed by the Laboratory of Infectious Disease in collaboration with the National Institute of Allergy and Infectious Diseases. The Matrix-M adjuvant is developed by Novavax.
The vaccine targets the EBV gp350 that is found on the surface of the virus and virus-infected cells. This protein is also the target for neutralizing antibodies found in the blood of people naturally infected with EBV.
Ferritin, a natural iron storage protein found in cells of all living species, is a reportedly promising vaccine platform because it can rapidly display proteins from targeted cells in dense arrays on its surface.
The adjuvant in the vaccine will enhance the immune response induced by the vaccine.
As of this writing, a trial has been planned to test the vaccine that will include 40 healthy volunteers between the ages of 18 and 29 years. Half of those participants have evidence of previous EBV infection while the other half do not.
The participants will be given a series of three 50-microgram injections of the experimental vaccine in the upper arm muscle. They will be monitored for 30 to 60 minutes after each dose. The second and third doses will be given 30 days and 180 days after the initial dose, respectively, with follow-up visits and phone calls conducted between each vaccination.
Participation is expected to last between 18 and 30 months and the trial is anticipated to last about 4 years.
Reference: National Institutes of Health. NIH launches clinical trial of Epstein-Barr virus vaccine. 2022. http://www.nih.gov/news-events/news-releases/nih-launches-clinical-trial-epstein.
DIABETES
New injectable approved
MOUNJARO (tirzepatide, Eli Lilly) has been approved by the FDA to improve glycemic control in adults with type 2 diabetes as an addition to diet and exercise.
MOUNJARO is a glucose-dependent insulinotropic polypeptide receptor and glucagon-like peptide-1 receptor agonist. In clinical trials, it was reportedly effective at improving blood glucose levels and more effective than other diabetes therapies.
Patients randomized to receive the maximum recommended dose (15 mg) had 1.6% lower A1C levels than placebo when used as a standalone treatment. Patients also had 1.5% lower A1C levels than placebo when used in combination with long-acting insulin.
Trials comparing MOUNJARO to other diabetes medications found that patients receiving 15 mg doses had a 0.5% lower A1C than semaglutide, 0.9% lower than insulin degludec, and 1.0% lower than insulin glargine.
Regarding patients with obesity, which was common among participants, the average weight loss with Mounjaro was 15 lb more than placebo when neither were used with insulin and 23 lb more than placebo when both were used with insulin.
The average weight loss among participants with MOUNJARO was 12 lb more than with semaglutide, 29 lb more than with insulin deguldec, and 27 lb more than with insulin glargine. Patients receiving insulin without MOUNJARO tended to gain weight throughout the studies.
MOUNJARO has not been studied in patients with a history of pancreatitis. It is not indicated for patients with type 1 diabetes mellitus.
MOUNJARO is administered once weekly subcutaneously in the abdomen, thigh, or upper arm, with or without meals. Injection sites should be rotated with each dose.
The starting dose is 2.5 mg, increasing to 5 mg after 4 weeks. After that, the dose may be increased by 2.5 mg after 4 weeks of the current dose if necessary up to 15 mg.
MOUNJARO is contraindicated in those with personal or family histories of medullary thyroid carcinoma; in those with Multiple Endocrine Neoplasia syndrome type 2; and those with a known serious hypersensitivity to tirzepatide or any excipients of MOUNJARO.
Prescribing information contains warnings of pancreatitis, hypoglycemia, acute kidney injury, hypersensitivity reactions, severe gastrointestinal disease, diabetic retinopathy complications in patients with a history of diabetic retinopathy, and acute gallbladder disease that may occur with the use of MOUNJARO.
The most common adverse reactions reported with the use of MOUNJARO include nausea, diarrhea, anorexia, vomiting, constipation, dyspepsia, and abdominal pain.
References: U.S. Food and Drug Administration. FDA approves novel, dual-targeted treatment for type 2 diabetes. http://www.fda.gov/news-events/press-announcements/fda-approves-novel-dual-targe.
MOUNJARO Prescribing Information. 2022.
INFECTIOUS DISEASE
New antibiotic approved for Helicobacter pylori (H. pylori)
VOQUENZA triple and dual paks have been approved by the FDA for the treatment of H. pylori in adults.
The triple paks contain vonoprazan, a potassium-competitive acid blocker; amoxicillin, a penicillin class antibacterial; and clarithromycin, a macrolide antimicrobial. The dual paks contain vonoprazan and amoxicillin. They are produced by Phathom Pharmaceuticals.
While the paks are indicated for the treatment of H. pylori infection in adults, to reduce the development of drug-resistant bacteria and maintain the effectiveness, they should only be used to treat or prevent infections proven or strongly suspected to be caused by bacteria.
The triple paks contain a carton of 14 daily administration packs for morning and evening dosing (Vonoprazan 20 mg tablets, Clarithromycin 500 mg tablets, and Amoxicillin 500 mg capsules). The dual paks contain the same minus clarithromycin.
The recommended dosage regimen for the triple pack is vonoprazan 20 mg plus amoxicillin 1,000 mg plus clarithromycin 500 mg, each twice daily (morning and evening, 12 hours apart) with or without food for 14 days. The recommended dosage regimen for the dual pak is vonoprazan 20 mg twice daily (morning and evening) plus amoxicillin 1,000 mg, three times a day (morning, midday, and evening), with or without food, for 14 days.
The paks are contraindicated in those with a known hypersensitivity to vonoprazan, amoxicillin or any other beta-lactams, clarithromycin, or any other macrolide antimicrobial and its components, and rilpivirine-containing products.
Due to the presence of clarithromycin in the triple paks, they are also contraindicated in those taking pimozide; lomitapide, lovastatin, and simvastatin; ergot alkaloids (ergotamine or dihydroergotamine); colchicine in renal or hepatic impairment; and those with a history of cholestatic jaundice/hepatic dysfunction.
Adverse reactions to the triple pak include dysgeusia, diarrhea, vulvovaginal candidiasis, headache, abdominal pain, and hypertension. Adverse reactions to the dual pak include diarrhea, abdominal pain, vulvovaginal candidiasis, and nasopharyngitis.
Reference: VOQUENZA Prescribing Information. 2022.
ASTHMA
Combination therapy more effective
The risk of severe asthma exacerbation is significantly lower in patients receiving a combination of albuterol and budesonide than albuterol alone.
In a multinational, phase 3, double-blind, randomized, event-driven trial, adults and adolescents older than 12 years of age were randomized 1:1:1 to receive either a high dose (180 mcg of albuterol and 160 mcg of budesonide; two actuations of 90 mcg and 80 mcg, respectively); a low dose (a fixed-dose combination of 180 mcg of albuterol and 80 mcg of budesonide; two actuations of 90 mcg and 40 mcg, respectively); or albuterol alone (180 mcg of albuterol; two actuations of 90 mcg). Children between 4 and 11 years old were randomly assigned to the lower-dose combination group or the albuterol-alone group.
The primary efficacy endpoint for the trial was the first event of severe asthma exacerbation in a time-to-event analysis performed by the intention-to-treat population.
Out of the 3,132 participants, 97% were at least 12 years old.
The risk of severe asthma exacerbation was calculated to be 26% lower in the higher-dose combination group than in the albuterol-alone group (hazard ratio, 0.74; 95% confidence interval [CI], 0.62 to 0.89; P = .001). Compared with the albuterol-alone group, the lower-dose combination group's hazard ratio was 0.84 (95% CI, 0.71 to 1.00; P =.052). Adverse events were reportedly similar in the three groups.
Reference: Papi A, Chipps BE, Beasley R, et al. Albuterol-Budesonide fixed-dose combination rescue inhaler for asthma. N Engl J Med. 2022;386(22):2071-2083. doi:10.1056/nejmoa2203163.