FDA Drug Approvals, Family Medicine — 2020 Midyear Review

August 14, 2020


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)


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 two 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 2020 Mar;40(3):241-254

Neurology 2020 Mar 31;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 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). A corroborating study (n=1811) showed similar results.

( N Engl J Med 2019 Jul 11;381(2):142-149

Lancet 2019 Aug 31;394(10200):737-745)

Ongentys (opicapone)

Opicapone is a once-daily, peripherally acting catechol-o-methyl transferase (COMT) inhibitor. COMT inhibitors decrease the conversion rate of levodopa to 3-O-methyldopa, and thereby prolong the levodopa half-life to reduce Parkinson disease  motor fluctuations. Opicapone is indicated as an adjunct to levodopa/carbidopa to reduce “OFF” episodes in patients with Parkinson disease.

Approval was based on the BIPARK-1 and BIPARK-2 phase 3 clinical studies, which included approximately 1000 patients. A significant reduction of daily OFF time and dyskinesia with opicapone 50 mg was observed when compared with placebo (P <.0001).

( Eur J Neurol 2019 Jul;26(7):953-960)

Tauvid (flortaucipir F18)

Flortaucipir F18 binds to aggregated tau protein. In brains of patients with Alzheimer disease , tau aggregates combine to form neurofibrillary tangles (NFTs), 1 of 2 components required for neuropathologic diagnosis of Alzheimer disease. It is indicated for use with positron-emission tomography (PET) imaging of the brain to estimate the density and distribution of aggregated tau NFTs in adults with cognitive impairment who are being evaluated for Alzheimer disease.

The safety and effectiveness were demonstrated in 2 clinical studies. In each study, 5 evaluators, blinded to clinical information, interpreted the flortaucipir F18 PET scan results as positive or negative. The first study included 156 terminally ill patients who agreed to undergo flortaucipir F18 PET imaging and to donate their brains after death. Of these patients, 64 died within 9 months of undergoing brain scanning. The evaluators' readings of these scans were compared with postmortem readings from independent pathologists blinded to scan results.

Evaluators reading the flortaucipir F18 PET scans had a "high probability" of correctly evaluating patients with tau pathology and had an "average-to-high probability" of correctly evaluating patients without tau pathology. Reader sensitivity ranged from 92% (95% confidence interval [CI], 80-97%) to 100% (95% CI, 91-100%). Specificity ranged from 52% (95% CI, 34-70%) to 92% (95% CI, 75-98%).

(Tauvid prescribing information)

Other neurology approvals

Bafiertam (monomethyl fumarate) - Indicated for relapsing forms of multiple sclerosis , to include clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease.

Cymbalta (duloxetine) - Indication for fibromyalgia now includes adolescents aged 13-17 years.

Fintepla (fenfluramine) - Reintroduced to US market with new indication for seizures associated with Dravet syndrome in patients aged 2 years or older.

Qutenza (capsaicin transdermal) - New prescription-strength product for neuropathic pain associated with postherpetic neuralgia.

Xywav (oxybate mixed salts) - New mixed-salt oxybate for narcolepsy with 92% lower sodium content.

Infectious Disease

Rukobia (fostemsavir)

Fostemsavir, a prodrug of temsavir, is a first-in-class glycoprotein 120 (gp120) attachment inhibitor. It binds directly to the gp120 subunit on the surface of the virus, and thereby blocks HIV from attaching to host immune system CD4+ T cells and other immune cells. It is indicated in combination with other antiretroviral drugs for treatment of HIV-1 infection in heavily treatment-experienced adults with multidrug-resistant HIV-1 infection in whom their current antiretroviral regimen failed because of resistance, intolerance, or safety considerations.

Approval was based on the BRIGHTE study (n=371 [including 99 participants in the nonrandomized cohort]). All participants had a viral load of 400 copies/mL or greater and 2 or fewer classes of antiretrovirals remaining at baseline. On day 8, participants treated with fostemsavir (n=203) had a significantly greater decrease in levels of HIV-RNA in their blood compared with those taking the placebo (n=69) (0.79 vs 0.17 log10 copies/mL decline, respectively; P <.0001). After day 8, all participants received fostemsavir with other antiretrovirals. After 24 weeks of fostemsavir plus other antiretrovirals, 53% achieved HIV-RNA suppression, where levels of HIV were low enough to be considered undetectable. After 96 weeks, 60% continued to have HIV-RNA suppression.

( N Engl J Med 2020 Mar 26;382(13):1232-1243)


Artesunate is an antimalarial artemisinin derivative. It is rapidly metabolized to the active metabolite, dihydroartemisinin (DHA). Artesunate and DHA, like other artemisinins, contain an endoperoxide bridge that is activated by heme iron that leads to oxidative stress, inhibition of protein and nucleic acid synthesis, ultrastructural changes, and decreased parasite growth and survival. Artesunate and DHA are active against the blood-stage asexual parasites and gametocytes of Plasmodium species, including the chloroquine-resistant strains.

Artesunate is administered intravenously and is indicated for adults and children for initial treatment of severe malaria. It should always be followed by a complete treatment course of an appropriate oral antimalarial regimen.

Artesunate IV was officially approved by the FDA in May 2020 (it was previously available from the CDC through an Investigative New Drug protocol). Approval was based the South East Asian Quinine Artesunate Malaria Trial (SEAQUAMAT) and the African Quinine Artesunate Malaria Trial (AQUAMAT). These 2 studies examined a total of 6886 patients and included adults, children, and pregnant women. Artesunate IV reduced mortality by 34.7% (P=.0002) and 22.5% (P=.002) compared with quinine in the SEAQUMAT and AQUAMAT studies, respectively.

(Lancet 2005 Aug 27-Sep 2;366(9487):717-25

Lancet 2010 Nov 13;376(9753):1647-57)

Other infectious disease approvals

Epclusa (sofosbuvir/velpatasvir) - Indicated for chronic hepatitis C virus infection in children aged 6 years or older or weighing at least 17 kg.

Recarbrio (imipenem/cilastatin/relebactam) - New indication for hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia.

Remdesivir - FDA granted an emergency use authorization for remdesivir to treat hospitalized patients with suspected or confirmed SARS CoV-2 infection and severe COVID-19 disease .

Sirturo (bedaquiline) - Indication for multidrug-resistant pulmonary tuberculosis expanded to include children aged 5 years or older.

Sivextro (tedizolid) - Indicated for acute bacterial skin and skin structure infections in patients aged 12 years or older.

Tivicay PD (dolutegravir) - Indicated for HIV infection in children aged 4 weeks or older who weigh at least 3 kg.

Zosyn (piperacillin/tazobactam) - Indication for nosocomial pneumonia expanded to include children as young as 2 months.


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.

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

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

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

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

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


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 .

Women’s Health

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.


Isturisa (osilodrostat)

Osilodrostat is an orally administered steroidogenesis inhibitor of 11-beta-hydroxylase, an enzyme that catalyzes the final step of cortisol synthesis in the adrenal cortex. It is indicated for Cushing disease in adults for whom pituitary surgery is not an option or has not been curative.

Approval of osilodrostat was based on the phase 3 LINC-3 clinical trial (n=137). It was a multicenter, double-blind, randomized withdrawal study following a 24-week, open-label, single-arm treatment phase. Open-label osilodrostat was initiated at 2 mg twice daily in 137 adults with Cushing disease and mean urinary free cortisol (mUFC; mean of three 24-h samples) greater than 1.5 times the upper limit of normal (ULN) (ULN=50 mcg/24 h), with dose adjustments every 2 weeks (dose range 1-30 mg BID) up to week 12 based on efficacy (if mUFC > ULN) and tolerability. At week 26, 71 eligible patients (mUFC equal or below ULN at week 24 without a dose increase after week 12) were randomized to continue osilodrostat (n=36) or matching placebo (n=35) for 8 weeks, followed by open-label osilodrostat until week 48. Patients who remained on treatment at week 26, but were not eligible for randomization, continued open-label osilodrostat (n=47).

At baseline, median (range) mUFC was 3.5 times the ULN (0.3-69.6) in enrolled patients. At the end of the randomized withdrawal period (week 34), significantly more patients maintained mUFC equal to or less than the ULN (without a dose increase after week 26) in the osilodrostat group than in the placebo group (86% vs 29%; odds ratio, 13.7; P <.001).

( J Endo Soc 2019 Apr-May;3(1; Suppl))


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 is 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, which 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 2019 Mar 14;380(11);1022-1032

JAMA 2019 Nov 12;322(18):1780-1788)

Other cardiovascular approvals

Brilinta (Ticagrelor) - New indication for risk reduction for patients with coronary artery disease who have not had a myocardial infarction or stroke.

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.


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