FDA Approvals, Highlights, and Summaries

February 24, 2021


Orladeyo (berotralstat)

Berotralstat is the first oral kallikrein inhibitor approved for prophylaxis of hereditary angioedema (HAE) attacks in patients aged 12 years and older. Kallikrein is a protease that cleaves high-molecular-weight-kininogen (HMWK) to generate cleaved HMWK and bradykinin, a potent vasodilator that increases vascular permeability resulting in swelling and pain associated with HAE. In patients with HAE caused by C1-inhibitor deficiency or dysfunction, normal regulation of plasma kallikrein activity is not present, which leads to uncontrolled increases in plasma kallikrein activity and results in angioedema attacks.

The APeX-2 phase 3 trial demonstrated a significant reduction in attack rate at both 110 mg (1.65 attacks per month; P=.024) and 150 mg (1.31 attacks per month; P <.001) compared with placebo (2.35 attacks per month). ( J Allergy Clin Immunol. October 21, 2020;S0091-6749)

Other notable approvals

Arcalyst (rilonacept) - New indication for maintenance of remission of deficiency of interleukin-1 receptor antagonist (DIRA) in adults and pediatric patients weighing at least 10 kg


Nexletol (bempedoic acid)

Bempedoic acid is a first-in-class adenosine triphosphate-citrate lyase (ACL) inhibitor that lowers low-density lipoprotein cholesterol (LDL-C) by inhibiting cholesterol synthesis in the liver. ACL is an enzyme upstream of 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA) reductase in the cholesterol biosynthesis pathway. Bempedoic acid and its active metabolite, ESP15228, require coenzyme A (CoA) activation by very long?chain acyl-CoA synthetase 1 (ACSVL1) to ETC-1002-CoA and ESP15228-CoA, respectively. ACSVL1 is expressed primarily in the liver, but absent in most peripheral tissues.

Bempedoic acid and the combination, bempedoic acid/ezetimibe, are indicated as an adjunct to diet and maximally tolerated statin therapy for adults with heterozygous familial hypercholesterolemia or established atherosclerotic cardiovascular disease who require additional lowering of LDL-C.

Approval of bempedoic acid was based on the phase 3 trials CLEAR Harmony and CLEAR Wisdom that included over 3000 patients. The addition of bempedoic acid to maximally tolerated statin therapy provided an average of 18% corrected LDL-C lowering. ( N Engl J Med. March 14, 2019;380(11);1022-1032; JAMA. November 12, 2019;322(18):1780-1788)

Other notable approvals

Brilinta (Ticagrelor) - New indication for risk reduction for patients with coronary artery disease who have not had a myocardial infarction or stroke; also indicated to reduce risk of stroke in patients with acute ischemic stroke or high-risk transient ischemic attack

Farxiga (dapagliflozin) - Indicated to reduce risk of cardiovascular death and hospitalization for heart failure in adults with heart failure (NYHA class II-IV) (with or without diabetes) with reduced ejection fraction

Trulicity (dulaglutide) - Indicated for primary and secondary risk reduction of major adverse cardiovascular events in adults with type 2 diabetes who have established cardiovascular disease or multiple risk factors


Xeglyze (abametapir)

Abametapir, a metalloproteinase inhibitor and topical pediculicide, is indicated for head lice infestation in adults and children aged 6 months and older.

Approval was supported in part by a double-blind, phase 2 trial in 50 patients with active head lice infestation who were randomized to receive a single treatment of abametapir lotion or vehicle (control) applied to scalp and hair for 10 minutes. Ovicidal efficacy was measured by recording the hatch rate of eggs collected from each subject’s hair before and after treatment and incubated for 14 days. With abametapir, 100% of treated eggs remained unhatched, compared with 64% for vehicle. Accounting for pretreatment hatch rates, the absolute reduction in egg hatching was 92.9% for abametapir versus 42.3% for vehicle (P <.0001). ( Glob Pediatr Health. February 22, 2019;6)

Two studies (n=704) showed that 81.5% of abametapir-treated individuals were free of lice 2 weeks after a single application, compared with 49.1% treated with vehicle (P <.001). ( Pediatr Dermatol. 2018;35(5):616-621)

Klisyri (tirbanibulin topical)

Tirbanibulin topical is indicated for actinic keratosis of the face or scalp. It is a microtubule inhibitor, although the mechanism by which it is effective for actinic dermatosis is unknown.

Approval was based on 2 phase 3 clinical trials (AK003 and AK004) that evaluated the safety and efficacy of tirbanibulin topical in adults (N=702) with facial or scalp actinic keratosis. The tirbanibulin-treated group achieved a higher percentage of complete clearance of actinic keratosis at day 57 (AK003, 44% vs 5%; AK004, 54% vs 13%) and partial clearance compared with placebo in both trials (AK003, 68% vs 16%; AK004, 76% vs 20%). (Klisyri prescribing information)

Winlevi (clascoterone topical)

Clascoterone topical is an androgen-receptor inhibitor indicated for acne vulgaris in patients aged 12 years and older. The exact mechanism of action by which it clascoterone is effective for acne is unknown. Laboratory studies suggest clascoterone competes with androgens, specifically dihydrotestosterone, for binding to the androgen receptors within the sebaceous gland and hair follicles.

Approval of clascoterone topical was supported by 2 phase 3 randomized trials including 1,440 patients. At week 12, treatment success rates showed statistically significant improvement for patients receiving clascoterone (18.4% and 20.3%) compared with the vehicle alone (9% and 6.5%). ( JAMA Dermatol, June 1, 2020;165(6):621-30)

Other notable approvals

Vectical (calcitriol topical) - Indication for plaque psoriasis expanded to include children aged 2 years and older (previously approved for adults)

Stelara (ustekinumab) - Indication for plaque psoriasis expanded to include children aged 6 years and older (previously approved for aged ≥12 years)

Ultravate lotion (halobetasol topical) - Indication expanded to include adolescents aged 12 years and older

Zilxi (minocycline topical) - New 1.5% product for rosacea

Qwo (collagenase clostridium histolyticum) - New indication for moderate-to-severe cellulite of the buttocks in women

Dupixent (dupilumab) - Indicated for moderate-to-severe atopic dermatitis not adequately controlled with topical prescription therapies or when those therapies are not advisable in children aged 6 years or older

Jublia (efinaconazole) - Indication for onychomycosis expanded to include children as young as 6 years

Taltz (ixekizumab) - Indication for plaque psoriasis expanded to include children aged 6 years or older

Eucrisa (crisaborole topical) - Indicated for mild-to-moderate atopic dermatitis in infants and children aged 3 months or older


Imcivree (setmelanotide)

Setmelanotide is a melanocortin-4 receptor agonist. MC4 receptors in the brain are involved in regulation of hunger, satiety, and energy expenditure. Setmelanotide is the first drug indicated for long-term weight management in patients aged at least 6 years with obesity due to rare genetic conditions (eg, proopiomelanocortin [POMC], proprotein convertase subtilisin/kexin type 1 [PCSK1], or leptin receptor [LEPR] deficiency).

Phase 3 clinical trials observed 80% of patients with obesity owing to POMC or PCSK1 deficiency achieved greater than 10% weight loss and 45.5% of patients with obesity due to LEPR deficiency achieved greater than 10% weight loss after 1 year of treatment. Additionally, hunger scores improved from baseline to 1 year. ( Lancet Diabetes Endocrinol. December 2020;8(12):960-970 and Imcivree prescribing information)

Other notable approvals

Saxenda (liraglutide) - Indication for adjunctive use for long-term weight management expanded to include adolescents

Qutenza (capsaicin transdermal) - New prescription-strength transdermal patch for neuropathic pain associated with diabetic peripheral neuropathy of the feet

Trulicity (dulaglutide) - Indicated for primary and secondary risk reduction of major adverse cardiovascular events in adults with type 2 diabetes who have established cardiovascular disease or multiple risk factors


Pizensy (lactitol)

Lactitol exerts an osmotic effect, causing an influx of water into the small intestine that results in a laxative effect in the colon. It is indicated for adults with chronic idiopathic constipation.

Approval was based on data from approximately 800 patients that included a 6-month placebo-controlled trial and a 3-month active-controlled trial with lubiprostone. Pizensy prescribing information

Other notable approvals

Suprep (sodium sulfate/potassium sulfate/magnesium sulfate) - Indication for colonoscopy bowel preparation expanded to include children aged 12 years and older

Sutab (sodium sulfate/magnesium sulfate/potassium chloride) - New oral tablet regimen for bowel preparation for colonoscopy


Vyepti (eptinezumab)

Eptinezumab is a humanized IgG1 monoclonal antibody specific for binding to the calcitonin gene-related peptide (CGRP) ligand. CGRP is thought to be causally involved in migraine pathophysiology. It is administered as a 30-minute intravenous infusion every 3 months for prevention of migraine.

Approval was based on 2 phase 3 trials, PROMISE-1 (n=665) and PROMISE-2 (n=1072). The percent of responders with at least 50% reduction of monthly migraine days (MMDs) from baseline was higher with eptinezumab (100 mg or 300 mg IV every 3 months) compared with placebo (P=.001). The trials also showed a higher percentage of patients achieved a 75% reduction in MMDs compared with placebo. ( Cephalalgia. March 2020;40(3):241-254; Neurology. March 31, 2020;94(3)e1365-1377)

Nurtec ODT (rimegepant)

Rimegepant is a calcitonin gene-related peptide (CGRP) antagonist. The oral disintegrating tablet is indicated for treatment of acute migraine with or without aura.

Rimegepant approval was supported by a phase 3 trial (n=1186) of patients with moderate-to-severe migraine, with a frequency of 2-8 attacks per month. The percentage of patients who were pain-free 2 hours after receiving rimegepant was 19.6% compared with and 12% in the placebo group (P <.001). The percentage of patients who were free from their most bothersome symptom 2 hours after rimegepant was 37.6% compared with 25.2% for placebo (P <.001). ( N Engl J Med. July 11, 2019;381(2):142-149) A corroborating study (n=1811) showed similar results. ( Lancet. August 31, 2019;394(10200):737-745)


Notable approvals

Xolair (omalizumab) - New indication for add-on maintenance treatment of nasal polyps in adults with inadequate response to nasal corticosteroids


Notable approvals

Spravato (esketamine intranasal) - New indication for depressive symptoms in adults with major depressive disorder with acute suicidal ideation or behavior

Hetlioz (tasimelteon) - New indication for nighttime sleep disturbances associated with Smith-Magenis syndrome in patients aged 3 years and older

Pulmonary Medicine

Notable approvals

Breztri (budesonide/formoterol/glycopyrrolate inhaled) - New triple-combination aerosol inhaler approved for chronic obstructive pulmonary disease

Trelegy Ellipta (umeclidinium bromide/vilanterol inhaled/fluticasone furoate inhaled) - New indication for maintenance treatment of asthma

Bronchitol (mannitol inhalation) - New indication and brand for adults with cystic fibrosis as add-on maintenance therapy


Notable approvals

Tremfya (guselkumab) - Indicated for active psoriatic arthritis

Xeljanz (tofacitinib) - Indicated for active polyarticular course juvenile idiopathic arthritis for children aged 2 years and older

Simponi Aria (golimumab) - New indication for active polyarticular course juvenile idiopathic arthritis in children aged 2 years and older; additionally, indication for psoriatic arthritis extended to include patients aged 2 years and older

Ilaris (canakinumab) - Treatment of active Still disease, including adult onset

Taltz (ixekizumab) - New indication for active nonradiographic axial spondyloarthritis with objective signs of inflammation

Cosentyx (secukinumab) - Also approved for nonradiographic axial spondyloarthritis


Gemtesa (vibegron)

Vibegron is indicated for overactive bladder with symptoms of urge urinary incontinence, urgency, and urinary frequency in adults. It is a selective beta-3 adrenergic receptor agonist. Activation of the beta-3 adrenergic receptor increases bladder capacity by relaxing the detrusor smooth muscle during bladder filling.

Approval was based on the EMPOWUR phase 3 clinical trial. Of 1,518 randomized patients, 90.4% completed the trial. At 12 weeks, micturition episodes decreased by an adjusted mean of 1.8 episodes per day for vibegron compared with 1.3 for placebo (P <.001) and 1.6 for tolterodine. Among incontinent patients, urge incontinence episodes decreased by an adjusted mean of 2 episodes per day for vibegron compared with 1.4 for placebo (P <.0001) and 1.8 for tolterodine. J Urol. August 2020;204(2):316-324

Oxlumo (lumasiran)

Lumasiran is a small interfering ribonucleic acid (RNAi) agent that reduces levels of glycolate oxidase (GO) enzyme by targeting hydroxyacid oxidase 1 mRNA in hepatocytes through RNA interference. Decreased GO enzyme levels reduce the amount of available glyoxylate, a substrate for oxalate production. It is the first drug approved by the FDA for primary hyperoxaluria type 1 (PH1) to lower urinary oxalate levels.

Approval was based on the ILLUMINATE-A and ILLUMINATE-B phase 3 trials. The randomized, placebo-controlled ILLUMINATE-A trial (n=39; ages 6-61 years) demonstrated a 65% reduction of 24-hour urinary oxalate levels in the lumasiran-treated group, compared with an average of 12% reduction in the placebo group. By month 6 of the study, 52% of the lumasiran-treated group reached a normal 24-hour urinary oxalate level, compared with no patients in the placebo group. ILLUMINATE-B, which was an open-label study of lumasiran treatment in 16 patients with PH1 younger than 6 years, showed an average 71% decrease in urinary oxalate by 6 months. (Oxlumo prescribing information)

Women's Health

Notable approvals

Oriahnn (elagolix and estradiol/norethindrone acetate) - Indicated for management of heavy menstrual bleeding associated with uterine leiomyomas (fibroids) in premenopausal women

Phexxi (lactic acid/citric acid/potassium bitartrate vaginal) - Intravaginal pH regulator for on-demand contraception


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