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Jan-2019-Drug-Intell January 2019 CLINICAL UPDATES, OUTCOMES, & REAL- WORLD EVIDENCE “Plans and PBMs Diabetes Recommendations for 2019 | ADA & ACC In December 2018, the American Diabetes Association (ADA) published the are accustomed to 2019 Standards of Medical Care in Diabetes[1], aligning its recommendations overly complex for cardiovascular risk reduction in people with type 2 diabetes (T2D) with those of the American College of Cardiology (ACC) for the first time. platforms that are Recommendation highlights include: the result of years 1. First-line therapy is Metformin and lifestyle management. of patches, fixes, 2. Switch to glucagon-like peptide 1 (GLP-1) agonists (e.g., Trulicity™, and workarounds. Tanzeum™, Victoza™) or sodium-glucose cotransporter 2 (SGLT2) The era of legacy inhibitors (e.g., Jardiance™, Invokana™, Farxiga™) if atherosclerotic PBM systems is cardiovascular disease, chronic kidney disease, or heart failure. now ending.” 3. For most patients who need an injectable medication, a GLP-1 receptor agonist should be the first choice ahead of insulin. - Jason Borschow Abarca President and CEO 4. Diabetes can now be diagnosed based on two abnormal test results in an interview with Forbes (fasting blood glucose, 2-h plasma glucose (2-h PG) value during a 75-g oral glucose tolerance test (OGTT), or A1C criteria) from the same sample (also from two different test samples but performed without delay). This may allow for an earlier diagnosis and treatment, as it will not be necessary to confirm with a second test if results exceed diagnostic thresholds. 5. ADA acknowledges that self-monitoring of blood glucose in patients with T2D who are not at risk for hypoglycemia (i.e., not taking insulin or sulfonylureas) is of limited benefit. 6. Drug costs are a major consideration in care throughout the guide. SEEING OPPORTUNITY READY FOR THESE HIGHLY ANTICIPATED DRUGS? Advanced or Metastatic Solid Tumors Cancers are traditionally treated based on their tissue of origin and pathologic classification. Yet, oncologic precision medicine just witnessed a breakthrough in November 2018 through FDA’s approval of Vitrakvi™ (larotrectinib; Bayer/Loxo Oncology) to treat solid tumors with neurotrophic tropomyosin receptor kinase (NTRK) gene fusions, regardless of cancer type. These fusions are found in about 90% of rare tumor types, accounting for 1% of cancers overall, but also occasionally found in common cancers. Vitrakvi™ achieved tumor-agnostic overall response rates (ORR) of 75-80%, with no treatment-related grade 3/4 adverse events (AEs), in a variety of advanced and metastatic pediatric and adult solid tumors such as breast invasive carcinoma, colon adenocarcinoma, lung cancer, thyroid cancer, and melanoma. Vitrakvi™ is just the first generation of competitive inhibitors of the tropomyosin receptor kinases (TRKs) to enter clinical development. In addition to Vitrakvi™, there is a variety of next-generation TRK inhibitors currently in track to be submitted to the FDA in 2019, including repotrectinib, entrectinib, merestinib, and sitravatinib, with phase 1 and 2 results that appear to overcome potential acquired resistance to Vitrakvi™. Progression-free Precision medicine survival (PFS) at one year was achieved by 55% of patients on Vitrakvi™ and ongoing treatment response was 71%. Median PFS just witnessed a has not yet been reached. Complete response was seen in 16%, a partial response in 64%, and stable disease in 13% of treated breakthrough in patients. Nausea, diarrhea, constipation, vomiting, and increased treating solid tumors. transaminase levels were grade 1/2 AEs in 15% of trial participants.[2] Hereditary Angioedema (HAE) Prophylaxis HAE is mainly caused by autosomal dominant mutations in the C1 esterase inhibitor (C1-INH). Low C1-INH levels (HAE Type 1) or dysfunctional C1-INH (HAE Type 2) lead to buildup of the potent vasodilator bradykinin, resulting in recurrent tissue swelling (angioedema) in various parts of the body, including laryngeal swelling and abdominal pain. HAE affects 1 in 50,000 persons, equally males and females, in all races and ethnicities. There are two human plasma-derived C1-INHs currently approved for long-term HAE prophylaxis, increasing C1-INH levels, and preventing accumulation of bradykinin and angioedema onset. Cinryze™ (Shire) is the intravenous C1-INH approved in October 2008 for patients ages six and older. On June 2017 FDA approved the subcutaneous (SC) C1-INH Haegarda™ (CSL Behring) for patients 12 and older. Takhzyro™ (lanadelumab; Shire) is a new SC monoclonal antibody approved on August 2018 for long-term prophylaxis in HAE patients ages 12 and older. Takhzyro™ inhibits plasma kallikrein, preventing formation of bradykinin and therefore decreasing the risk of developing angioedema. Table 1 summarizes the percentage reduction in monthly HAE attack rates for these long-term prophylaxis therapies over 16-26 weeks, compared to placebo.[3] TABLE 1. CLINICAL EFFICACY OF MEDICATIONS FOR LONG-TERM HAE PROPHYLAXIS Hereditary Angioedema (HAE) % Reduction in Total HAE Annual Prophylaxis Agents Attack Compared to Placebo WAC C1 Esterase Inhibitors | Human Plasma-Derived Cinryze™ (Shire) 1,000 IU IV every 3-4 days 51%* $539,670 Haegarda™ (CSL Behring) 60 IU/kg SC twice weekly 84% $509,792 Kallikrein Inhibitor | Monoclonal Antibody Takhzyro™ ( lanadelumab; Shire) 300mg SC biweekly 87% $565,557 Abbreviations: HAE, Hereditary Angioedema; IV, Intravenous; SC, Subcutaneous; WAC, Wholesale acquisition cost. *Estimated from results presented over 12 weeks. 2 HAVE YOU MET THE NEW MEDS ON THE BLOCK? OCT-NOV 2018[4] Manufacture 2018 Drug Category For the treatment of: r Approval New Drugs Approved Ultomiris™ (ravulizumab) Alexion Long-acting C5 21-Dec Paroxysmal nocturnal hemoglobinuria. Intravenous Pharma complement inhibitor. Elzonris™ (tagraxofusp) Stemline 21-Dec CD123-directed cytotoxin. Blastic plasmacytoid dendritic cell neoplasm. Intravenous Therapeutics Inbrija™ (levodopa) Inhalation Acorda Oral inhalation formulation Off episodes in people with Parkinson’s disease 21-Dec Powder Therapeutics of the approved levodopa. taking a carbidopa-levodopa regimen. Asparlas™ (calaspargase pegol) Servier Asparagine specific As a component of a multi-agent chemotherapy 20-Dec Intravenous Pharma enzyme. regimen for the treatment of ALL. Motegrity™ (prucalopride) Selective serotonin type 4 Shire 14-Dec Chronic idiopathic constipation in adults Tablets receptor agonist. Herzuma™ (trastuzumab-pkrb) HER2/neu receptor IV Teva Pharma 14-Dec HER2-overexpressing breast cancer. antagonist. [Herceptin’s biosimilar] Mayne Certain fungal infections including Tolsura™ (itraconazole) Capsules 11-Dec Azole antifungal. Pharma US blastomycosis, histoplasmosis and aspergillosis. Dextenza™ (dexamethasone) Ocular Corticosteroid 30-Nov Post-surgical ocular inflammation and pain. Ophthalmic Insert Therapeutix intracanalicular insert. Astellas Patients who have relapsed or have refractory Xospata™ (gilteritinib) Tablets 28-Nov FLT3/ AXL kinase inhibitor. Pharma US AML with a FLT3 mutation. Firdapse™ (amifampridine Catalyst Nonspecific, voltage- 28-Nov Lambert Eaton Myasthenic Syndrome. phosphate) Tablets Pharma potassium channel blocker. Truxima™ (rituximab-abbs) IV CD20-directed cytolytic Teva Pharma 28-Nov Adult patients with non-Hodgkin’s lymphoma. [Rituxan’s biosimilar] antibody. Vitrakvi™ (larotrectinib) Capsules Selective tropomyosin- Loxo Oncology 26-Nov Solid tumors harboring NTRK-fusion proteins. and Oral Solution receptor kinase inhibitor. Hedgehog pathway For the combination treatment of adults aged Daurismo™ (glasdegib) Tablets Pfizer 21-Nov inhibitor. ≥75 years with newly diagnosed AML. Gamifant™ (emapalumab) Novimmune Interferon gamma (IFN-γ) For patients with primary hemophagocytic 20-Nov Intravenous SA blocking antibody. lymphohistiocytosis (HLH). Aemcolo™ (rifamycin) Delayed- Cosmo Broad spectrum, orally Traveler’s diarrhea caused by noninvasive 16-Nov Release Tablets Technologies non-absorbable antibiotic. strains of Escherichia coli. New Indications 1st-line BRCA-mutated advanced ovarian cancer, Oral poly-ADP ribose Lynparza™ (olaparib) Tablets AstraZeneca 19-Dec metastatic breast cancer, recurrent epithelial polymerase inhibitor. and fallopian tube or primary peritoneal cancer. MCC, melanoma, NSCLC, HNSCC, HCC, Hodgkin Keytruda™ (pembrolizumab) Human PD-1 receptor Merck 19-Dec lymphoma, mediastinal large B-cell lymphoma, Intravenous blocking antibody. urothelial carcinoma, gastric & cervical cancer. Nplate™ (romiplostim) Thrombopoietin mimetic Pediatric and adult thrombocytopenia in chronic Amgen 14-Dec Subcutaneous peptibody. immune ITP in patients aged ≥ 1 year. Tecentriq™ (atezolizumab) 1st-line in metastatic NSCLC without EGFR or Genentech 6-Dec PD-L1 blocking antibody. Intravenous ALK mutations and for SCLC and bladder cancer. B-cell lymphoma-2 New AML in patients aged ≥ 75 years, and 2nd Venclexta™ (venetoclax) Tablets Genentech 21-Nov inhibitor. line in CLL and small lymphocytic lymphoma. New CD30-expressing peripheral T-cell Adcetris™ (brentuximab) Seattle CD30-directed antibody- 16-Nov lymphoma, Hodgkin, ALCL or mycosis Intravenous Genetics drug conjugate. fungoides. Promacta™ (eltrombopag) Thrombopoietin receptor 1st-line in thrombocytopenia with severe aplastic Novartis 16-Nov Tablets agonist. anemia, chronic immune ITP or hepatitis C. Abbreviations: ALCL, Anaplastic large cell lymphoma; ALK, Anaplastic lymphoma kinase; ALL, Acute lymphoblastic leukemia; AML, Acute myeloid leukemia; AXL, A receptor tyrosine kinase;
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