National CooperativeRx constantly monitors the pharmaceutical pipeline. As treatment options change, it’s important to know how those changes could impact your plan and which drugs bring the highest value. Our quarterly NCRx Pipeline Reports highlight some of the newest therapies coming to market and are not intended to imply formulary placement or coverage by CVS Caremark.
SPN-812 (Viloxazine): Viloxazine is a new non-stimulant medication to treat attention-deficit hyperactivity disorder (ADHD). It increases serotonin, norepinephrine, and dopamine and offers an additional treatment option to the 20% of children and adolescents who are not adequately relieved of ADHD symptoms from other ADHD medications. Stimulants, including amphetamines and methylphenidate, are still the most effective for ADHD but come with significant side effects such as increases in blood pressure and heart rate, appetite suppression, and insomnia. Stimulants also come with strict rules on prescribing and dispensing which make them more difficult to obtain. Viloxazine reduced ADHD symptoms by about 40% on the ADHD rating scale by the end of study, compared to a 25% improvement with placebo.1 It also appears to have a fast onset of action, with most patients seeing improvement within one week. However, the 40% improvement still does not bring the symptom score across the threshold defining remission. The most significant side effects were drowsiness (8.9%), decreased appetite (6.0%), and headache (5.4%). The drug was used safely for 25 years in Europe for depression, which is being considered in the US as well.
Anticipated Launch: FDA decision expected in November of 2020 with launch in early 2021.
Impact: Low. Stimulants will likely remain the first-line treatment. ADHD affects 11% of children, 8.7% of adolescents and 4.4% of adults.2
Price: Currently unknown. Given the variety of generic alternatives, Viloxazine is likely to be assigned a more competitive price for a brand-name product.
ALKS-3831 (olanzapine/samidorphan): This new product is a combination of an existing antipsychotic medication, olanzapine, and an opioid receptor antagonist, samidorphan. The drug is being considered by the FDA for schizophrenia and bipolar I disorder. Olanzapine is one of the most effective antipsychotics for schizophrenia but frequently causes significant weight gain. This can lead to the development of metabolic syndrome, defined as coexisting high blood pressure, high blood sugar, high cholesterol and increased waist size. In a six-month clinical trial, olanzapine/samidorphan therapy resulted in a 4.21% increase in weight from baseline, compared to 6.59% for olanzapine alone.3 Additionally, only 17.8% of patients in the olanzapine/samidorphan group experienced greater or equal to 10% weight gain, compared to 29.8% in the olanzapine group. Reduction in symptoms of schizophrenia was similar between the two groups. The most common side effects were drowsiness and dry mouth, both of which occurred at a higher rate in the olanzapine/samidorphan group. The FDA has scheduled a meeting on October 9, 2020 to discuss the potential for drug interactions between samidorphan and opioids. There are many antipsychotic medications on the market with varying risks of weight gain, cholesterol increase and diabetes. For most patients, that means there will be plenty of competing therapy alternatives to olanzapine/samidorphan. This drug will likely be used in patients who have failed other therapies or who have done well on olanzapine but are at high risk of metabolic syndrome.
Anticipated Launch: Late 2020 or early 2021.
Impact: Moderate in the schizophrenia and bipolar I population. There are an estimated 750,000-1.9 million people living in the US with schizophrenia4 and another 3 million people with bipolar I disorder.
Price: Currently unknown.
Evrenzo® (roxadustat): Evrenzo® is the first in a new class of hypoxia-inducible factor prolyl hydroxylase inhibitors to treat anemia in chronic kidney disease. It is an oral drug while Aranesp® and Retacrit®, current standards of therapy, are injectable medications. In a meta-analysis of clinical trials, Evrenzo® was found to increase hemoglobin by 1.99g/dL over placebo in non-dialysis dependent patients and by 0.52g/dL over erythropoietin in dialysis patients.5 It has also shown potential for positive effects on inflammation, lipids, and blood pressure in patients with chronic kidney disease. While the list of advantages is quite promising, there are some important safety concerns which will need careful review. Given the drug’s mechanism of action, some of the concerns include elevated potassium, tumor growth, kidney disease progression, blood clots and hepatitis progression.6 Despite any possible risks, an oral option will be a welcome addition and, at a minimum, offer an additional option for patients who fail Aranesp®-like drugs. The drug is under review by the FDA for dialysis and non-dialysis dependent patients. It is already approved in China for both dialysis and non-dialysis patients and in Japan for dialysis patients only.
Anticipated Launch: Late 2020 or early 2021.
Impact: Low initially — perhaps low to moderate as safety concerns become more clear. There are 4 million people in the US with chronic kidney disease.
Price: Currently unknown, but likely to be comparable to products like Aranesp® at around $1,200 per month.
Inclisiran: Inclisiran will be the newest addition to the PCSK9 class of drugs, joining Repatha® and Praluent®. Incisiran works by blocking production of PCSK9, in contrast to Repatha® and Praluent® which bind existing PCSK9. Perhaps the most attractive attribute of inclisiran is its maintenance dose injected every six months compared to every two to four weeks for Repatha® and Praluent®. In clinical trials, inclisiran reduced LDL (bad cholesterol) by about 40% in patients with familial hypercholesterolemia7, a reduction similar to that of Repatha® and Praluent®. There were no major safety issues found with inclisiran. While the PCSK9 drugs did not have the market uptake that was expected initially, they seem to be building a robust safety and efficacy profile over time. Combined with recent reductions in price, this may contribute to increased utilization in this class.
Anticipated Launch: Quarter four of 2020.
Impact: Moderate. There are over 14 million people in the US eligible for a PCSK9.8
Price: Currently unknown, but it will likely be close to the existing PCSK9 inhibitors at around $500 per month.
- Nasser A, Liranso T, Adewole T, Joshi Jones N, Findling RL, Schwabe S. A Phase III, Randomized, Placebo-Controlled Trial to Assess the Efficacy and Safety of Once-Daily SPN-812 (Viloxazine Extended-Release) in the Treatment of Attention-Deficit/Hyperactivity Disorder in School-age Children. Clin Ther July 25, 2020.
- National Institute of Mental Health: Attention-Deficit/Hyperactivity Disorder (ADHD). Accessed at https://www.nimh.nih.gov/health/statistics/attention-deficit-hyperactivity-disorder-adhd.shtml on September 17, 2020.
- Correll CU, Newcomer JW, Silverman B, et al. Effects of Olanzapine Combined With Samidorphan on Weight Gain in Schizophrenia: A 24-Week Phase 3 Study. Am J Psychiatry August 14, 2020.
- National Institute of Mental Health: Accessed at https://www.nimh.nih.gov/health/statistics/schizophrenia.shtml on September 16, 2020.
- Liua J, Zhangb A, Hayden JC, et al. Roxadustat (FG-4592) treatment for anemia in dialysis-dependent (DD) and not dialysis-dependent (NDD) chronic kidney disease patients: A systematic review and meta‐analysis. Pharmacolol Res 2020 May; 155:104747.
- Sanghani NS and Haase VH. HIF-prolyl hydroxylase inhibitors in renal anemia: current clinical experience. Adv Chronic Kidney Dis. 2019 Jul; 26(4): 253–266.
- Raal FJ, Kallend D, Ray KK, et al. Inclisiran for the Treatment of Heterozygous Familial Hypercholesterolemia. N Engl J Med 2020; 382:1520-1530.
- Cheng W, Gaudette E, Goldman DP. PCSK9 Inhibitors Show Value for Patients and the U.S. Healthcare System. Value Health 2017 Dec; 20(10): 1270–1278.
