Cardiology
Leqvio (inclisiran)
Inclisiran is a double-stranded small interfering ribonucleic acid (siRNA), conjugated on the sense strand with triantennary N-acetylgalactosamine (GalNAc) to facilitate uptake by hepatocytes. In hepatocytes, inclisiran utilizes the RNA interference mechanism and directs catalytic breakdown of mRNA for proprotein convertase subtilisin kexin type 9 (PCSK9). This increases low-density lipoprotein (LDL-C) receptor recycling and expression on the hepatocyte cell surface, which increases LDL-C uptake and lowers LDL-C levels in the circulation.
Inclisiran is indicated as an adjunct to diet and maximally tolerated statin therapy for adults with heterozygous familial hypercholesterolemia (HeFH) or clinical atherosclerotic cardiovascular disease (ASCVD) who require additional LDL-C lowering. The subcutaneous injection is administered on Day 1, at Day 90, and then every 6 months thereafter.
A total of 1561 and 1617 patients underwent randomization in the phase 3 ORION-10 and ORION-11 trials, respectively. At day 510, inclisiran (plus maximally tolerated statin therapy) reduced LDL cholesterol levels by 52.3% in the ORION-10 trial and by 49.9% in the ORION-11 trial (P< 0.001 for all comparisons vs. placebo). N Engl J Med. 2020 Apr 16;382(16):1507-1519
Evkeeza (evinacumab)
Evinacumab is a recombinant human monoclonal antibody that binds to and inhibits angiopoietin–like 3 (ANGPTL3). ANGPTL3 inhibits lipoprotein lipase and endothelial lipase, thereby reducing lipid metabolism. Evinacumab inhibits ANGPTL3 and results in increased lipid metabolism, leading to decreased low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL_C), and triglycerides. Evinacumab is indicated as an adjunct to other LDL-C–lowering therapies for homozygous familial hypercholesterolemia in adults and adolescents aged 12 years and older.
Approval was based on the phase 3 ELIPSE trial (n = 65). The study found that patients undergoing stable lipid-lowering treatment in whom an intravenous infusion of evinacumab was administered every 4 weeks achieved, by week 24, a 47.1% relative reduction in their LDL-C level, as compared to a 1.9% increase seen in patients treated with a placebo (P<.001). N Engl J Med . 2020;383:711-720
Verquvo (vericiguat)
Vericiguat stimulates soluble guanylate-cyclase (sGC), the intracellular receptor for endogenous nitric oxide (NO), which catalyzes cyclic guanosine monophosphate (cGMP) production; cGMP plays a role in the regulation of vascular tone, cardiac contractility, and cardiac remodeling. By directly stimulating sGC, independently of and synergistically with NO, vericiguat augments levels of intracellular cGMP, leading to smooth muscle relaxation and vasodilation. Vericiguat is indicated to reduce the risk of cardiovascular death and heart failure (HF) hospitalization, following hospitalization for HF or need for outpatient intravenous diuretics, in adults with symptomatic chronic HF and ejection fraction less than 45%.
Results from the phase 3 VICTORIA trial (n = 5050) showed that in patients with symptomatic chronic HF (New York Heart Association class II-IV) and left ventricular ejection fraction of less than 45%, vericiguat was superior to placebo in reducing the risk of cardiovascular death or heart failure hospitalization. These results were based on a time-to-event analysis (hazard ratio, 0.9; 95% confidence interval, 0.82-0.98; P=.02) and demonstrated an adverse event profile similar to placebo. N Engl J Med . 2020; 382:1883-1893
Kerendia (finerenone)
Finerenone is indicated to reduce risk of sustained eGFR decline, end-stage kidney disease, cardiovascular death, nonfatal myocardial infarction, and hospitalization for heart failure in adults with chronic kidney disease (CKD) associated with type 2 diabetes mellitus. It is the first nonsteroidal mineralocorticoid receptor (MR) antagonist to be approved for this purpose.
Approval was based on the FIDELIO-DKD trial, a placebo-controlled study that involved over 5700 patients with type 2 diabetes mellitus to whom the maximum-tolerated dose of renin-angiotensin system inhibitor (RASI) was already being administered. However, until more data on finerenone is gathered, RASIs and SGLT-2 inhibitors will be the preferred agents for slowing chronic kidney disease in type 2 diabetes mellitus. N Engl J Med. 2020 Dec 3;383(23):2219-2229
Other cardiology approvals
Jardiance (empagliflozin) - Indicated to reduce the risk of cardiovascular death plus hospitalization for heart failure in adults with heart failure and reduced ejection fraction.
Xarelto (rivaroxaban) - Indicated, in combination with aspirin, to reduce risk of major thrombotic vascular events in patients with peripheral artery disease (PAD), including those who have recently undergone a lower extremity revascularization procedure due to symptomatic PAD.
Praluent (alirocumab) - Indicated as an adjunct to other low-density lipoprotein cholesterol (LDL-C)–lowering therapies in adults with homozygous familial hypercholesterolemia to reduce LDL-C.
Entresto (sacubitril/valsartan) - Indication for heart failure expanded to include adults with preserved left ventricular ejection fraction.
Arcalyst (rilonacept) - Interleukin-1 inhibitor for treatment of recurrent pericarditis and to reduce risk of future recurrence in adults and children aged 12 years and older.
Roszet (rosuvastatin/ezetimibe) - New combination indicated to reduce low-density lipoprotein cholesterol in patients with primary nonfamilial hyperlipidemia or homozygous familial hypercholesterolemia.
Neurology
Qulipta (atogepant)
Atogepant is an oral calcitonin gene–related peptide (CGRP) receptor antagonist indicated for preventive treatment of episodic migraine. CGRP is thought to be causally involved in migraine pathophysiology.
Drug approval was based on the ADVANCE phase 3 trial. Patients received once-daily atogepant or placebo. Among 873 participants who were included in the efficacy analysis, 214 received atogepant 10 mg, 223 received atogepant 30 mg, 222 received atogepant 60 mg, and 214 were in the placebo group. Mean number of migraine days per month at baseline ranged from 7.5 to 7.9 in the 4 groups. Changes from baseline over 12 weeks were -3.7 days with 10-mg atogepant, -3.9 days with 30-mg atogepant, -4.2 days with 60-mg atogepant, and -2.5 days with placebo (P<0.001 for all comparisons with placebo). N Engl J Med. 2021 Aug 19; 385:695-706
Vyvgart (efgartigimod alfa)
Efgartigimod alfa is an Fc receptor antagonist indicated for generalized myasthenia gravis (gMG) in adults who are anti-acetylcholine receptor (AChR) antibody positive. Myasthenia gravis is an autoimmune disease in which IgG autoantibodies are formed against the nicotinic AChR or other components of the neuromuscular junction. Efgartigimod alfa is an antibody fragment that targets the neonatal Fc receptor (FcRn), thereby reducing circulating IgG. FcRn prolongs IgG half-life. Antagonizing FcRn causes IgG catabolism, resulting in reduced overall IgG and pathogenic autoantibody levels, while avoiding widespread immunosuppression.
Efgartigimod was effective and well-tolerated in the phase 3, randomized, placebo-controlled ADAPT trial, which enrolled 187 adults with gMG regardless of acetylcholine receptor antibody status. For 26 weeks, 84 patients were randomly assigned to receive efgartigimod 10 mg/kg and 83 to receive matching placebo. Both treatments were administered as 4 weekly IV infusions per cycle. The process was repeated as needed, depending on clinical response no sooner than 8 weeks after initiation of the previous cycle. Treatment with efgartigimod reduced disease burden and improved strength and quality of life in patients with gMG across 4 MG-specific scales. In addition, these benefits were observed early and were reproducible and durable. Lancet Neurol. 2021 Jul;20(7):526-536
Ponvory (ponesimod)
Ponesimod is a sphingosine 1-phosphate (S1P) receptor 1 modulator that binds with high affinity to S1P receptor 1 and blocks the capacity of lymphocytes to regress from lymph nodes, reducing the number of lymphocytes in peripheral blood. Ponesimod is indicated for relapsing forms of multiple sclerosis (MS), including clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease.
Approval for ponesimod was based on a head-to-head phase 3 trial (n = 1133). In that trial, ponesimod demonstrated superior efficacy in significantly reducing annual relapse by 30.5% compared to teriflunomide in patients with relapsing MS. Over the study period, 71% of patients treated with ponesimod had no confirmed relapses, as compared to 61% in the teriflunomide group. JAMA Neurol. 2021 May 1;78(5):558-567
Amondys 45 (casimersen)
Casimersen is an antisense oligonucleotide of the phosphorodiamidate morpholino oligomer (PMO) subclass. PMO binds to exon 45 of dystrophin pre-mRNA, resulting in exclusion of this exon during mRNA processing in patients with genetic mutations that are amenable to exon 53 skipping. Casimersen is indicated for Duchenne muscular dystrophy in patients with a confirmed mutation amenable to exon 45 skipping.
The ESSENCE trial—a placebo-controlled confirmatory trial to support the casimersen approval—is ongoing and expected to conclude in 2024. In the study, patients who received casimersen showed a significantly greater increase in dystrophin protein levels from baseline to Week 48 of treatment, as compared to those who received placebo. Study of SRP-4045 and SRP-4053 in DMD Patients (ESSENCE)
Aduhelm (aducanumab)
Aducanumab is a monoclonal antibody that targets beta-amyloid and binds to aggregated forms of beta-amyloid. The FDA granted accelerated approval for aducanumab based on the reduction in amyloid-beta plaques observed in patients treated for Alzheimer disease. The prescribing information specifies approval for patients with mild cognitive impairment or a mild dementia stage of disease, which was the population studied in the clinical trials. The prescribing information states that continued approval is contingent upon verification of clinical benefit in confirmatory trial(s).
Accelerated approval was based on 2 phase 3 trials. In a letter released by the FDA, the rationale for approval was explained. One of the clinical trials (EMERGE) was the first to show that high-dose aducanumab reduced amyloid-beta plaques—a hallmark finding in the brains of patients with Alzheimer disease—and slowed cognitive decline. The second trial (ENGAGE) showed no benefit of aducanumab versus placebo, at low or high doses. Debate continues regarding this approval. The materials for the FDA Peripheral and Central Nervous System Drugs Advisory Committee Meeting provide detailed analyses of these phase 3 trials.
Nulibry (fosdenopterin)
Fosdenopterin is indicated to reduce the risk of mortality in patients with molybdenum cofactor deficiency type A (MoCD-A), a rare disease. Fosdenopterin provides an exogenous source of cyclic pyranopterin monophosphate (cPMP). MoCD-A is caused by a mutation in the molybdenum cofactor synthesis 1 gene (MOCS1), which causes a deficiency in molybdenum cofactor production. The exogenous intermediate substrate cPMP provided by the drug is subsequently converted to molybdenum cofactor, which is required for the activation of essential enzymes (eg, sulfite oxidase) to reduce the levels of neurotoxic sulfites. Decreased sulfite oxidase activity is thought to cause the severe and rapidly progressive CNS damage observed in patients with MoCD-A.
Fosdenopterin is the first effective therapy for patients with MoCD. A study in 15 neonates showed restoration of molybdenum cofactor-dependent enzyme activities following fosdenopterin and greatly improved neurodevelopmental outcome when fosdenopterin was started sufficiently early. Lancet. 2015 Nov 14;386(10007):1955-1963
Other neurology approvals
Botox (onabotulinumtoxinA) - Six additional muscle groups approved for upper limb spasticity in adults.
Gocovri (amantadine) - Gained FDA approval as adjunctive treatment to levodopa/carbidopa for Parkinson disease in patients experiencing "off" episodes.
Nurtec ODT (rimegepant) - Indication for migraine expanded to include preventive therapy. Originally approved for acute treatment.
Infectious Disease
Livtencity (maribavir)
Maribavir is an antiviral that elicits its activity by competitive inhibition of the protein kinase activity of human cytomegalovirus (CMV) enzyme pUL97, which inhibits protein phosphorylation. It is indicated for treatment of posttransplant CMV infection/disease that is refractory to treatment with or without genotypic resistance (eg, ganciclovir, valganciclovir, cidofovir, foscarnet) in adults and pediatric patients aged 12 years and older who weigh at least 35 kg.
The phase 3 SOLSTICE trial randomized hematopoietic-cell and solid-organ transplant recipients 2:1 to receive maribavir (n = 235) or investigator-assigned therapy (IAT; valganciclovir/ganciclovir, foscarnet, or cidofovir [n = 117]). Significantly more patients in the maribavir versus IAT group achieved CMV clearance by week 8 (55.7% vs 23.9%; P<.001) and maintained through week 16 (18.7% vs 10.3%; P=.01). Clin Infect Dis. 2021 Dec 2
Comirnaty (COVID-19 vaccine, mRNA-Pfizer)
COVID-19 vaccine, mRNA-Pfizer is the first vaccine to gain full approval in the United States for prevention of COVID-19 disease for individuals aged 16 years and older. Since its August 2021 approval, the emergency use authorization for the vaccine has been amended to include children aged 5 years and older, third-dose administration for those aged 12 years and older who are immunocompromised, and booster doses for individuals aged 16 years and older.
Approval was based on a multinational phase 3 trial (n = 43,448). Vaccine efficacy was 95% against the original SARS-CoV-2 strain at 7 days after dose 2, and no serious safety concerns were observed. Updated data through 6 months (March 13, 2021) showed vaccine efficacy against COVID-19 was 91.3%. Vaccine variants (eg, delta) and waning efficacy prompted implementation of adding a booster dose to be administered 6 months after the 2-dose primary series. N Engl J Med 2021;385:1761-1773
Vaxneuvance and Prevnar 20 (15-valent and 20-valent pneumococcal vaccines)
Pneumococcal vaccine 15-valent and pneumococcal vaccine 20-valent contain all serotypes in the 13-valent pneumococcal vaccine, plus additional serotypes responsible for pneumococcal disease cases and deaths in the United States. Each vaccine is indicated for active immunization for prevention of pneumonia and invasive disease caused by Streptococcus pneumoniae in adults aged 18 years and older.
Additional serotypes in the pneumococcal vaccine 15-valent include 22F and 33F.
Additional serotypes in pneumococcal vaccine 20-valent include 8, 10A, 11A, 12F, 15B, 22F, and 33F.
The CDC Pneumococcal Vaccines Work Group has issued a working document on how the newest pneumococcal vaccines are planned to be incorporated into the adult immunization schedule.
TicoVac (tick-borne encephalitis vaccine)
Tick-borne encephalitis vaccine is indicated in adults and children aged 1 year and older for prevention of tick-borne encephalitis caused by Flaviviridae, including European or Western tick-borne encephalitis virus (transmitted by Ixodes ricinus), Siberian tick-borne encephalitis virus (transmitted by I persulcatus), and Far-Eastern tick-borne encephalitis virus, formerly known as Russian spring-summer encephalitis virus (transmitted by I persulcatus). It is administered as a 3-dose primary series.
Seropositivity rates at Day 21 after the third vaccination were above 99% for all age groups in Study 209 and above 98% in Study 213 and Study 690601. Three years after the primary 3-dose series, seropositivity ranged from 82.9 to 100% depending on age. Prescribing Information
Fexinidazole
Fexinidazole is a nitroimidazole antiprotozoal drug indicated for treatment of African trypanosomiasis (HAT; sleeping sickness) caused by Trypanosoma brucei gambiense in adults and children aged 6 years and older who weigh at least 20 kg. It is indicated for stage 1 (hemolymphatic) and stage 2 (meningoencephalitic) HAT.
Results from 2 single-arm trials in adults and pediatric patients aged 6-15 years supported FDA approval. Fexinidazole demonstrated efficacy of nearly 100% at 12 months. Lancet Glob Health. 2021 Jul;9(7)
Cabenuva (cabotegravir/rilpivirine) and Vocabria (cabotegravir)
Cabotegravir/rilpivirine is a combination of HIV-1 integrase strand transfer inhibitor (INSTI) and non-nucleoside reverse transcriptase inhibitor (NNRTI), which are copackaged as 2 separate intramuscular (IM) injections. Cabotegravir/rilpivirine is indicated as a complete regimen for treatment of HIV-1 infection in adults to replace a current stable antiretroviral therapy regimen in those who are virologically suppressed (HIV-1 RNA <50 copies/mL) with no history of treatment failure and with no known or suspected resistance to either cabotegravir or rilpivirine. It is initiated as a once-monthly IM injection following lead-in therapy with oral cabotegravir (Vocabria) plus rilpivirine (Edurant) for a least 1 month.
The safety and efficacy of cabotegravir/rilpivirine were established through 2 randomized, open-label, controlled clinical trials in 1182 HIV-infected adults who were virologically suppressed (HIV-1 RNA <50 copies/mL) before initiation of the treatment. Patients in both trials continued to show virologic suppression at the conclusion of each study, and no clinically relevant change from baseline in CD4+ cell counts was observed. N Engl J Med. 2020 Mar 19;382(12):1112-1123 ; N Engl J Med. 2020 Mar 19;382(12):1124-1135
Tembexa (brincidofovir)
Brincidofovir is a prodrug of cidofovir. Brincidofovir effectively penetrates cells via its lipid conjugate, releasing the nucleotide analog cidofovir, which then acts to inhibit viral replication. Cidofovir diphosphate selectively inhibits orthopoxvirus DNA polymerase–mediated viral DNA synthesis by incorporation of cidofovir into the growing viral DNA chain. This results in reductions in the rate of viral DNA synthesis. It is indicated for treatment of human smallpox disease caused by variola virus in adult and pediatric patients, including neonates.
The drug gained approval under the FDA's animal rule. Approval was based on efficacy data in 2 lethal orthopoxvirus animal models of human smallpox disease: the rabbit pox model (New Zealand white rabbits infected with rabbit pox virus) and the mouse pox model (BALB/c mice infected with ectromelia virus). In the pivotal studies in each model, brincidofovir resulted in statistically significant survival benefit versus placebo following delayed treatment after animals were infected with a lethal viral dose. Tembexa prescribing information
Other infectious disease approvals
Apretude (cabotegravir) - Every 2 month IM administration for preexposure prophylaxis (PrEP) in adults and adolescents weighing at least 35 kg to reduce the risk of sexually acquired HIV-1 infection.
Solosec (secnidazole) - New indication approved for treatment of trichomoniasis, to treat partners of infected patients simultaneously in order to prevent reinfection.
Shingrix (zoster vaccine recombinant) - Indication for shingles immunization expanded to include adults aged 18 years and older with increased risk of herpes zoster owing to immunodeficiency or immunosuppression caused by a known disease or therapy.
Natroba (spinosad) - New indication approved for scabies in adults and children aged 4 years and older.
Vaxchora (cholera vaccine) - Use for immunization against Vibrio cholerae serogroup 01 expanded to include children aged 2 years and older.
Rapivab (peramivir) - Indication for acute uncomplicated influenza expanded to include children as young as 6 months.
COVID-19 Emergency Use Authorizations
Oral antivirals
Molnupiravir : Treatment of mild-to-moderate COVID-19 in high-risk adults who test positive.
Paxlovid (nirmatrelvir/ritonavir) : Treatment of mild-to-moderate COVID-19 in high-risk adults and adolescents aged 12 years and older who test positive.
Vaccines
Booster dose authorized for adults aged 18 years and older at least 5 months after an mRNA vaccine or at least 2 months after the Janssen vaccine.
Third primary-series dose at least 1 month after second dose in adults who have undergone solid-organ transplantation or have a condition considered to have equivalent level of immunocompromise.
Booster dose authorized for individuals aged 18 years and older at least 5 months after an mRNA vaccine or at least 2 months after the Janssen vaccine.
Homologous booster dose authorized for adolescents aged 12-17 years at least 5 months after their primary 2-dose series with the Pfizer COVID-19 vaccine (not for heterologous use in this age group).
2-dose primary series approved for children aged 5 years and older.
Third primary-series dose at least 1 month after second dose in individuals aged 5 years and older who have undergone solid-organ transplantation or have a condition considered to have equivalent level of immunocompromise.
COVID-19 vaccine-Janssen (Johnson & Johnson)
Booster dose authorized for adults aged 18 years and older at least 2 months after completing primary vaccination with the Janssen vaccine.
Heterologous booster authorized in adults at least 5 months after receiving an mRNA vaccine.
Monoclonal antibodies
Treatment of mild-to-moderate coronavirus disease 2019 (COVID-19) in high-risk adults and children, including neonates.
Postexposure prophylaxis for high-risk adults and children, including neonates who are not fully vaccinated or are not expected to mount an adequate immune response.
REGEN-COV (casirivimab/imdevimab)
Treatment of mild-to-moderate coronavirus disease 2019 (COVID-19) in high-risk individuals aged 12 years and older.
Postexposure prophylaxis (PEP) for high-risk individuals aged 12 years and older who are not fully vaccinated or are not expected to mount an adequate immune response.
Treatment of mild-to-moderate coronavirus disease 2019 (COVID-19) in high-risk individuals aged 12 years and older.
Evusheld (tixagevimab and cilgavimab)
Preexposure prophylaxis of individuals aged 12 years and older who are moderately-to-severely immunocompromised owing to a medical condition or medications/treatment and may not mount an adequate immune response to COVID-19 vaccination or who have a history of severe adverse reactions to a COVID-19 vaccine and/or component(s)
Note: Depending on viral variants, distribution of certain monoclonal antibodies may be paused because of decreased efficacy.
Gastroenterology
Bylvay (odevixibat)
Odevixibat is a first-in-class ileal bile acid transport inhibitor (IBATi). It acts locally in the distal ileum to decrease reuptake of bile acids and increase clearance of bile acids through the colon, thereby reducing bile acid serum concentration. It is indicated for pruritus in patients with progressive familial intrahepatic cholestasis (PFIC) aged 3 months and older.
Approval was supported by data from the Demonstrate Efficacy and Safety of A4250 in Children With Progressive Familial Intrahepatic Cholestasis (PEDFIC) types 1 and 2 phase 3 trials. In PEDFIC 1, a randomized, double-blind, placebo-controlled study, odevixibat showed improvement of pruritus and serum bile acid compared with placebo. PEDFIC 2, a long-term, open-label phase 3 extension study, showed sustained reductions in serum bile acids, as well as improvements in pruritus assessments, growth, and other markers of liver function in patients treated up to 48 weeks. AASLD The Liver Meeting 2021. 2021 Nov 12-15
Livmarli (maralixibat)
Maralixibat is another IBATi that gained approval for cholestatic pruritus in adults and children aged 1 year and older with Alagille syndrome. Approval was based on the ICONIC study and 5 years of data from supportive studies in 86 patients with Alagille syndrome. On average, patients who received maralixibat for 22 weeks maintained pruritus reduction, whereas those in the placebo group who were withdrawn from maralixibat after Week 18 returned to baseline pruritus scores by Week 22. Lancet. 2021 Oct 30;398(10311):1581-1592
Other gastroenterology approvals
Dartisla ODT (glycopyrrolate) - New oral disintegrating tablet for adults to reduce symptoms of peptic ulcer as an adjunct to treatment.
Zeposia (ozanimod) - New indication approved for adults with moderately to severely active ulcerative colitis.
Psychiatry
Lybalvi (olanzapine/samidorphan)
Olanzapine/samidorphan is indicated for treatment of schizophrenia in adults. It is also approved for bipolar I disorder as monotherapy or as an adjunct to lithium or valproate. Olanzapine acts through a combination of dopamine and serotonin type 2 antagonism. Samidorphan is an opioid antagonist and mitigates weight gain associated with olanzapine.
Approval was based on the ENLIGHTEN clinical trials. Olanzapine is associated with metabolic changes, including hyperglycemia, dyslipidemia, and weight gain. The ENLIGHTEN trials showed the combination provided sustained antipsychotic efficacy with minimal effects on weight, waist circumference, and metabolic parameters. Am J Psychiatry. 2020 Dec 1;177(12):1168-1178
Azstarys (serdexmethylphenidate/dexmethylphenidate)
Serdexmethylphenidate/dexmethylphenidate is a fixed-dose combination of the prodrug of dexmethylphenidate, serdexmethylphenidate, and immediate-release dexmethylphenidate. This combination provides extended drug levels. It is indicated for attention deficit hyperactivity disorder (ADHD) in adults and children aged 6 years and older. Efficacy was assessed by Swanson, Kotkin, Agler, M-Flynn, and Pelham (SKAMP)–combined scores compared with baseline and at 0.5, 1, 2, 4, 8, 10, 12, and 13 hours post dose. Results showed statistically significant improvement of SKAMP-combined scores compared to placebo. Azstarys prescribing information
Qelbree (viloxazine)
Viloxazine is indicated for treatment of attention deficit hyperactivity disorder (ADHD) in children and adolescents aged 6-17 years. The mechanism of action by which viloxazine affects ADHD is unclear; however, it may be by selectively inhibiting norepinephrine reuptake. Approval was based on 3 phase-3 placebo-controlled trials that included over 1000 participants. Patients taking viloxazine had statistically significant improvement in ADHD Rating Scale 5 and Clinical Global Impressions I scores as compared to placebo. Qelbree prescribing information
Other psychiatry approvals
Caplyta (lumateperone) - New indication for depressive episodes associated with bipolar I or II disorder (bipolar depression) in adults, as monotherapy and as adjunctive therapy with lithium or valproate.
Xywav (calcium/magnesium/potassium/sodium oxybates) - New indication for idiopathic hypersomnia in adults.
Kloxxado (naloxone intranasal) - New formulation that delivers 8 mg per actuation, as compared to older products that deliver 2 mg or 4 mg per actuation.
Pulmonology
Tezspire (tezepelumab)
Tezepelumab is a first-in-class human monoclonal antibody immunoglobulin G2-lambda that inhibits thymic stromal lymphopoietin (TSLP). It is indicated for add-on maintenance treatment of severe asthma in adults and pediatric patients aged 12 years and older.
Approval was based on the NAVIGATOR phase 3, multicenter, randomized, double-blind, placebo-controlled trial. Patients (age, 12-80 years) were randomly assigned to receive tezepelumab (210 mg) or placebo subcutaneously every 4 weeks for 52 weeks. Of 1061 patients who underwent randomization, 529 were assigned to receive tezepelumab and 532 to receive placebo. The annualized rate of asthma exacerbations was 0.93 with tezepelumab and 2.10 with placebo (P<0.001). Additionally, in patients with a blood eosinophil count less than 300 cells per microliter, the annualized rate was 1.02 with tezepelumab and 1.73 with placebo (P<0.001). At Week 52, improvements were greater with tezepelumab than with placebo with respect to the prebronchodilator FEV1 (0.23 vs. 0.09 liters; P<0.001). N Engl J Med. 2021 May 13;384(19):1800-1809
Other pulmonology approvals
Prograf (tacrolimus) - Received FDA approval for prophylaxis of organ rejection in lung transplant recipients in combination with other immunosuppressants.
Tyvaso (treprostinil inhaled) - New indication granted for treatment of adults with pulmonary hypertension associated with interstitial lung disease (World Health Organization Group 3) to improve exercise ability.
Actemra (tocilizumab) - New indication approved for adults to slow the rate of decline in pulmonary function in adults with systemic sclerosis–associated interstitial lung disease.
Dermatology
Adbry (tralokinumab)
Tralokinumab is an interleukin-13 (IL-13) inhibitor that blocks IL-13–induced responses (eg, release of proinflammatory cytokines, chemokines, IgE). It is indicated for moderate-to-severe atopic dermatitis in adults who are not adequately controlled with topical prescription therapies or in whom those therapies are not advisable.
Results from the phase 3 ECZTRA clinical trials showed tralokinumab to be superior to placebo at 16 weeks of treatment and tolerated for up to 52 weeks. Br J Dermatol. 2021 Mar;184(3):437-449
Other dermatology approvals
Otezla (apremilast) - Indicated for plaque psoriasis expanded to include any severity in adults who are candidates for phototherapy or systemic therapy.
Opzelura (ruxolitinib topical) - First JAK inhibitor topical dosage form. Indicated for topical short-term and noncontinuous long-term treatment of mild-to-moderate atopic dermatitis in nonimmunocompromised patients aged 12 years and older whose disease is not adequately controlled with topical prescription therapies or when those therapies are not advisable.
Twyneo (tretinoin/benzoyl peroxide) - New combination approved for acne vulgaris in patients aged 9 years and older.
Endocrinology
Nexviazyme (avalglucosidase alfa)
Avalglucosidase is a recombinant acid alpha-glucosidase (GAA) indicated for late-onset Pompe disease in patients aged 1 year and older. GAA is deficient in Pompe disease, which leads to a buildup of glycogen in skeletal and cardiac muscle cells, causing weakness and premature death from respiratory failure or heart failure.
Approval was based on the COMET phase 3 trial that compared avalglucosidase alfa (n = 51) with alglucosidase alfa (n = 49). Clinically meaningful improvement with avalglucosidase-alfa therapy over alglucosidase alfa was observed in respiratory function, ambulation, and functional endurance. Lancet Neurol. 2021 Dec;20(12):1012-1026
Kerendia (finerenone)
Finerenone is indicated to reduce risk of sustained estimated glomerular filtration rate (eGFR) decline, end-stage kidney disease, cardiovascular death, nonfatal myocardial infarction, and hospitalization for heart failure in adults with chronic kidney disease (CKD) associated with type 2 diabetes mellitus. It is the first nonsteroidal mineralocorticoid receptor (MR) antagonist to be approved for this purpose.
Approval was based on the FIDELIO-DKD trial, a placebo-controlled study that involved over 5700 patients with type 2 diabetes mellitus to whom the maximum-tolerated dose of renin-angiotensin system inhibitor (RASI) was already being administered. However, until more data on finerenone are gathered, RASIs and SGLT-2 inhibitors will be the preferred agents for slowing CKD in type 2 diabetes mellitus. N Engl J Med. 2020 Dec 3;383(23):2219-2229
Recorlev (levoketoconazole)
Levoketoconazole is the purified 2S,4R enantiomer of ketoconazole. Levoketoconazole inhibits key steps in cortisol and testosterone synthesis. It is indicated for treatment of endogenous hypercortisolemia in adults with Cushing syndrome for whom surgery is not an option or has not been curative.
Results from the open-label phase 3 SONICS trial and the phase 3 LOGICS double-blind, randomized, controlled trial showed levoketoconazole led to sustained normalization of mean 24-hour urinary free cortisol (mUFC) and improvement in glycemic control that was more pronounced in patients with diabetes mellitus. Front Endocrinol 2021 Apr 7;12 and J Endocr Soc 2021 May 3; 5(Suppl 1): A526
Zegalogue (dasiglucagon)
Dasiglucagon is a ready-to-use, stable glucagon analog indicated for severe hypoglycemia in pediatric and adult patients with diabetes mellitus. It is a glucagon receptor agonist that increases blood glucose concentration by activating hepatic glucagon receptors, thereby stimulating glycogen breakdown and release of glucose from the liver.
Other endocrinology approval
Wegovy (semaglutide) - New distinct brand and indication as an adjunct to a reduced-calorie diet and increased physical activity for long-term weight management in adults who are obese (body mass index [BMI] ≥30 kg/m2) or overweight (BMI 27 kg/m2) with at least 1 weight-related comorbid condition (eg, hypertension, type 2 diabetes mellitus, dyslipidemia).
Nephrology and Urology
Korsuva (difelikefalin)
Difelikefalin is a peripherally restricted agonist of kappa opioid receptors thought to be essential in modulating pruritus. The drug is indicated for moderate-to-severe pruritus associated with chronic kidney disease in adults undergoing hemodialysis.
Results from the phase-3 KALM-1 trial showed 51.9% of patients in the difelikefalin group had at least a 3-point decrease in the 24-hour Worst Itching Intensity Numerical Rating Scale (WI-NRS), as compared to 30.9% in the placebo group. N Engl J Med. 2020 Jan 16;382(3):222-232
Kerendia (finerenone)
Finerenone is indicated to reduce risk of sustained estimated glomerular filtration rate (eGFR) decline, end-stage kidney disease, cardiovascular death, nonfatal myocardial infarction, and hospitalization for heart failure in adults with chronic kidney disease (CKD) associated with type 2 diabetes mellitus. It is the first nonsteroidal mineralocorticoid receptor (MR) antagonist to be approved for this purpose.
Approval was based on the FIDELIO-DKD trial, a placebo-controlled study that involved over 5700 patients with type 2 diabetes to whom the maximum-tolerated dose of renin-angiotensin system inhibitor (RASI) was already being administered. However, until more data on finerenone are gathered, RASIs and SGLT-2 inhibitors will be the preferred agents for slowing CKD in type 2 diabetes mellitus. N Engl J Med. 2020 Dec 3;383(23):2219-2229
Lupkynis (voclosporin)
Voclosporin is an oral calcineurin inhibitor indicated in combination with a background immunosuppressive regimen for treatment of active lupus nephritis in adults.
The AURA-LV phase 3 trial randomized patients to placebo or an induction regimen that combined voclosporin with mycophenolate mofetil and low-dose oral corticosteroids. At 24 weeks, 32.6% of the low-dose voclosporin group achieved complete renal response (CRR), and 27.3% in the high-dose voclosporin group achieved CRR, as compared to 19.3% in the placebo group. CRR rate in the low-dose and high-dose voclosporin groups was also higher than that of placebo at 48 weeks. Kidney. Jan;95(1):219-231
The AURORA phase 3 trial compared the efficacy and safety of voclosporin (23.7 mg twice daily) with placebo in combination with mycophenolate and low-dose oral corticosteroids. At 1 year, the renal response rate was higher in the voclosporin group than in the placebo group (40.8% vs 22.5%; odds ratio, 2.65; P<.001). In addition, the median time to the achievement of a urine protein-to-creatinine ratio below 0.5 mg/mg showed significant clinical improvement with voclosporin when compared to placebo (169 vs 372 days; P<.001). Lancet. 2021 May 29;397(10289):2070-2080
Other nephrology and urology approvals
Tarpeyo (budesonide) - Delayed-release capsule indicated to reduce proteinuria (increased protein levels in the urine) in adults with primary immunoglobulin A (IgA) nephropathy at risk of rapid disease progression.
Entadfi (finasteride/tadalafil) - New fixed-dose combination indication for benign prostatic hypertrophy.
Farxiga (dapagliflozin ) - Indication approved to reduce risk of sustained estimated glomerular filtration rate decline, end-stage kidney disease, cardiovascular death, and hospitalization for heart failure in adults with chronic kidney disease who are at risk of progression.
Myrbetriq (mirabegron) - FDA approval gained for neurogenic detrusor overactivity in children aged 3 years and older.
Botox (onabotulinumtoxinA) - New indication approved for neurogenic detrusor overactivity in children aged 5 years and older who have an inadequate response to or are intolerant of anticholinergic medications.
Ophthalmology
Tyrvaya (varenicline intranasal)
Varenicline intranasal is indicated for treatment of signs and symptoms of dry eye disease. Varenicline binds to highly selective heteromeric subtype(s) of the nicotinic acetylcholine receptor, which produces agonist activity and activates the trigeminal parasympathetic pathway resulting in increased production of basal tear film. The parasympathetic nervous system controls tear film homeostasis, partially via the trigeminal nerve, which is accessible within the nose.
Approval was supported by the ONSET-2 phase 3 trial (n = 758). A statistically significantly greater percentage of patients achieved a 10-mm improvement or more in Schirmer’s test score at Week 4 in both varenicline intranasal treatment groups compared to vehicle (0.6 mg/mL, 47.3%; 1.2 mg/mL, 49.2%; vs. vehicle, 27.8%; P<0.0001 for both doses). Ophthalmology. 2021 Nov 9
Other ophthalmology approvals
Vuity (pilocarpine ophthalmic) - New strength and indication approved for presbyopia in adults.
Dextenza (dexamethasone ophthalmic insert ) - New indication for ocular itching associated with allergic conjunctivitis.
Susvimo (ranibizumab intravitreal implant) - Indicated for treatment of neovascular (wet) age-related macular degeneration (ARMD) in adults who have previously responded to at least 2 intravitreal injections of a vascular endothelial growth factor (VEGF) inhibitor.
Byooviz (ranibizumab intravitreal injection) - First biosimilar to Lucentis approved for ARMD.
Verkazia (cyclosporine ophthalmic) - Indicated for vernal keratoconjunctivitis in adults and children aged 4 years and older.
Additional approvals across specialties
Nucala (mepolizumab) - New indication for add-on maintenance treatment of chronic rhinosinusitis with nasal polyps (CRSwNP) in adults with inadequate response to nasal corticosteroids.
Anavip (Crotalidae immune FAB equine) - Indication for treatment of snake envenomation expanded to include additional North American pit vipers.
Humira (adalimumab) - Indication for treatment of moderately to severely active ulcerative colitis expanded to include children 5 years of age and older.
Zeposia (ozanimod) - New indication approved for adults with moderately to severely active ulcerative colitis.
Tyvaso (treprostinil inhaled) - New indication granted for treatment of adults with pulmonary hypertension associated with interstitial lung disease (World Health Organization Group 3) to improve exercise ability.
Actemra (tocilizumab) - New indication approved for adults to slow the rate of decline in pulmonary function in adults with systemic sclerosis–associated interstitial lung disease.
Carbaglu (carglumic acid) - Approval granted for adjunctive therapy to standard of care for acute hyperammonemia due to propionic acidemia or methylmalonic acidemia in adults and children.
Brexafemme (ibrexafungerp) - New oral antifungal agent indicated for vulvovaginal candidiasis in adult and postmenarchal women.
Nextstellis (estetrol/drospirenone) - First oral contraceptive approved to contain estetrol (EF), a synthetic analog of native estrogen.
Saphnelo (anifrolumab) - New interferon antagonist that blocks type-1 IFN signaling indicated for systemic lupus erythematosus.
Tavneos (avacopan) - New complement 5a receptor antagonist approved for ANCA-associated vasculitis.
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Cite this: FDA Approvals, Highlights, and Summaries: Health Care Practitioners - Medscape - Feb 17, 2022.
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