Lippincott ^® NursingCenter ^®

The observational study looked at claims data on 581,451 Medicare beneficiaries (mean age, 77 years; 50.2% women) with atrial fibrillation who initiated treatment with a DOAC between January 2013 and November 2018. Apixaban was given to 353,879 patients (61%); 227,572 patients (39%) received rivaroxaban. About 23.1% of patients (n = 134,393) received a reduced dose of either drug. The claims data was examined for evidence of the primary outcome, a composite of major ischemic events (stroke and systemic embolism) and major hemorrhagic events (intracerebral hemorrhage, other intracranial bleeding, and fatal extracranial bleeding).

The effectiveness of the two drugs was similar, but new users of rivaroxaban had a greater risk of a range of adverse outcomes compared with those started on apixaban. Through median follow-up of about 6 months, the rate of the primary outcome was higher with rivaroxaban (16.1 per 1,000 person-years) vs. apixaban (13.4 per 1,000 person-years). Breaking down the composite shows that rivaroxaban was associated both with more major ischemic events than apixaban (8.6 vs. 7.6 per 1,000 person-years; hazard ratio [HR], 1.12) and with more major hemorrhagic events (7.5 vs. 5.9 per 1,000 person-years; HR, 1.26). Other key outcomes also favored apixaban: fatal extracranial bleeding (1.4 per 1,000 person-years with rivaroxaban vs. 1.0 per 1,000 person-years with apixaban; HR, 1.41), nonfatal extracranial bleeding (39.7 per 1,000 person-years with rivaroxaban vs. 18.5 per 1,000 person-years with apixaban; HR, 2.07), fatal ischemic or hemorrhagic events (4.5 vs. 3.3 per 1,000 person-years; HR, 1.34), and total mortality (44.2 vs. 41.0 per 1,000 person-years; HR, 1.06). The risk of the primary outcome was higher with rivaroxaban whether the patients received a reduced dose (27.4 vs. 2.1 per 1,000 person-years; HR, 1.28) or a standard dose (13.2 vs. 11.4 per 1,000 person-years; HR, 1.13).

This new analysis, because of its size, allowed investigators to examine differences in events that occurred less frequently, to combine ischemic and hemorrhagic events to get a risk-benefit picture, and to include analysis of different dosage strengths. These results demonstrate that although the two drugs are comparable in efficacy, apixaban is superior in safety. (Neale, T. (2021). Apixaban appears safer, more effective than rivaroxaban in Medicare study. TCTMD. Retrieved January 2022 from https://www.tctmd.com/news/apixaban-appears-safer-more-effective-rivaroxaban-medicare-study; Ray, W. A., et al. (2021). Association of rivaroxaban vs apixaban with major ischemic or hemorrhagic events in patients with atrial fibrillation. JAMA, 326(23), 2395–2404. Retrieved January 2022 from https://jamanetwork.com/journals/jama/article-abstract/2787319)

HIBISCUS I and II followed up on findings of a phase 2 study that indicated that etrolizumab significantly improved induction of clinical remission compared to placebo. The HIBISCUS studies, identically designed, multicenter, phase 3, randomized, double-blind, placebo-controlled and active-controlled studies, enrolled patients with moderate to severe ulcerative colitis, with a Mayo Clinic total score of 6 to 12 and endoscopic subscore of 2 or greater, rectal bleeding subscore of 1 or greater, and a stool frequency subscore of 1 or greater, who hadn’t previously been treated with TNF blockers. Patients were randomly assigned to subcutaneous etrolizumab 105 mg once every 4 weeks (n = 144 in HIBISCUS I and 143 in HIBISCUS II), to subcutaneous adalimumab 160 mg on day 1, 80 mg at week 2, and 40 mg at weeks 4, 6, and 8 (n = 142 in HIBISCUS I and 143 in HIBISCUS II), or to placebo (n = 72 in HIBISCUS I and 72 in HIBISCUS II).

The studies tested for induction of remission at week 10, defined as a Mayo Clinic total score of 2 or lower, with individual subscores of 1 or lower, including a rectal bleeding subscore of 0. Posted analysis of both studies were examined for several clinical and endoscopic endpoints. Etrolizumab was found to be significantly superior to placebo for induction of remission in HIBISCUS I, but not in HIBISCUS II. In HIBISCUS I, 28 patients (19.4%) in the etrolizumab group and 5 patients (6.9%) in the placebo group were in remission by week 10. On pooled analysis, treatment with etrolizumab was not superior to the TNF blocker adalimumab for induction of remission, endoscopic improvement, clinical response, histologic remission, or endoscopic remission.

LAUREL, a randomized, placebo-controlled, double-blind, phase 3 study, examined etrolizumab and compared it to placebo for maintenance of remission. The study enrolled adults with an established diagnosis of moderate to severe ulcerative colitis for at least 3 months, corroborated by clinical and endoscopic evidence. After an open-label induction phase, where 359 patients received subcutaneous etrolizumab 105 mg once every 4 weeks, if the participant had a clinical response at week 10, they were enrolled in the maintenance phase. The study found that 214 patients had such response, and were randomly assigned to receive subcutaneous etrolizumab 105 mg once every 4 weeks (n = 108) or placebo (n = 106) until week 62. At week 62, 32 patients (29.6%) in the etrolizumab group and 21 patients (20.6%) in the placebo group were in remission, a difference that is not clinically significant. (Rubin, D. T., et al. (2021). Etrolizumab versus adalimumab or placebo as induction therapy for moderately to severely active ulcerative colitis (HIBISCUS): Two phase 3 randomised, controlled trials. Lancet Gastroenterol Hepatol, 7(1), 17–27. Retrieved January 2022 from https://www.thelancet.com/journals/langas/article/PIIS2468-1253(21)00338-1/fulltext;

Vermeire, S, et al. (2021). Etrolizumab for maintenance therapy in patients with moderately to severely active ulcerative colitis (LAUREL): A randomized, placebo-controlled, double-blind, phase 3 study. Lancet Gastroenterol Hepatol, 7(1), 28–37. Retrieved January 2022 from https://www.thelancet.com/journals/langas/article/PIIS2468-1253(21)00295-8/fulltext)

The Bespoke Gene Therapy Consortium, or BGTC, will focus on adeno-associated virus (AAV) vectors, one of the safest platforms for gene delivery. BGTC aims to make AAV vector technology more accessible, pursuing an understanding of the life cycle of AAV, thereby facilitating optimization of vector generation and delivery. In addition, the consortium aims to streamline regulatory requirements: Because AAV vectors have been used before in clinical trials, it’s hoped that their use will shorten the path from animal models to human clinical trials. Working with the FDA, the consortium will explore methods of streamlining the FDA approval process for safe, effective gene therapies.

The consortium includes the NIH in general as well as various components, including the National Institute for Neurological Disorders and Stroke and National Human Genome Research Institute, the FDA, and 15 partners. These partners include 10 pharma companies, including Biogen, Janssen, and Spark Therapeutics, and 5 nonprofits, including The Alliance for Regenerative Medicine, National Organization for Rare Disorders, CureDuchenne, American Society of Gene and Cell Therapy, and the National Institute for Innovation in Manufacturing Biopharmaceutics. The members of the consortium will contribute about $76 million for 5 years to support the BGTC-funded projects, with about half coming from NIH institutes and centers. BGTC will fund research to support 4 to 6 clinical trials, focusing on different rare diseases. It’s hoped that this approach will have substantial positive impacts on the larger gene therapy field. (Philippidis, A. (2021). National Institutes of Health, U.S. Food and Drug Administration, 15 partners to accelerate development of rare disease gene therapies. Human Gene Therapy, 32 (No. 23-24). Retrieved January 2022 from https://www.liebertpub.com/doi/full/10.1089/hum.2021.29188.bfs; Foundation for NIH. (n.d.). Accelerating Medicines Partnership® Bespoke Gene Therapy Consortium (AMP® BGTC). Retrieved January 2022 from https://fnih.org/our-programs/AMP/BGTC)