New FDA Drug Approvals in 2020 by Indication: Part 1

This special section of First Report Managed Care includes data on the new molecular entities and new therapeutic biological products approved by the US Food & Drug Administration’s Center for Drug Evaluation and Research in 2020. Per the FDA website, “Some of these products are innovative new products that never have been used in clinical practice…This listing does not contain vaccines, allergenic products, blood and blood products, plasma derivatives, cellular and gene therapy products, or other products approved in 2020 by the Center for Biologics Evaluation and Research.” All data from this section has been taken directly from the FDA.

This part 1 page includes approvals in dermatology, endocrinology, gastroenterology, genetic diseases, hematology, infectious diseases, and neurology. You can find approval listings for oncology, ophthalmology, pain management, and procedural medicine in part 2 here. 

DERMATOLOGY

WINLEVI (clascoterone)
Manufacturer: Cassiopea Spa
Approval Date: August 26, 2020

FDA approved Winlevi to treat acne vulgaris in patients 12 years and older.

The approval of Winlevi was based on evidence published in two clinical trials of 1440 patients with acne vulgaris aged 9 to 58 years. Patients applied Winlevi or vehicle (placebo) cream twice daily for 12 weeks. Neither the patients nor the health care providers knew which treatment was being given until after the trial was completed. The benefit of Winlevi compared with placebo was assessed after 12 weeks of treatment using the Investigator’s Global Assessment score that measures disease severity (on a scale from 0 to 4) and a decrease in the number of acne lesions. More patients achieved a reduction in the number of acne and clear, or almost clear, skin after 12 weeks of treatment with Winlevi compared with patients treated with vehicle cream.

The most common side effects of Winlevi are reddening, itching, and scaling or dryness of the skin being treated. It may cause local skin irritation, adrenal gland suppression, and elevated serum potassium.

Winlevi is a cream that should be applied to the affected skin area twice a day.

XEGLYZE (abametapir)
Manufacturer: Dr. Reddy’s Laboratories 
Approval Date: July 24, 2020

FDA approved Xeglyze to treat head lice in patients 6 months of age and older.

The approval of Xeglyze was based on data from two identical clinical trials of 699 patients with head lice aged 6 months and older. About half of all enrolled patients were randomly assigned to Xeglyze and the other half to placebo. Xeglyze lotion or placebo lotion were applied once as a 10-minute treatment to infested hair. The benefit of Xeglyze in comparison to placebo was assessed after 1, 7, and 14 days by comparing the counts of patients in each group who were free of live lice. About 80% of patients treated with Xeglyze were free of live lice compared with about 50% of patients treated with placebo.

The commonly observed adverse effects included skin redness, rash, skin burning sensation, skin inflammation, vomiting, eye irritation, skin itching, and hair color changes. Xeglyze contains benzyl alcohol which may cause serious injury if accidentally ingested or used in patients younger than 6 months.

Xeglyze is a lotion applied once to dry hair.
 

ENDOCRINOLOGY

DOJOLVI (triheptanoin)
Manufacturer: Ultragenyx Pharmaceutical Inc
Approval Date: June 30, 2020

FDA approved Dojolvi to treat molecularly long-chain fatty acid oxidation disorders (LC-FAOD).

The approval of Dojolvi was supported by data from three clinical trials in which both adult and pediatric patients with LC-FAOD were enrolled. Trial 1 and Trial 2 were used to evaluate the side effects of Dojolvi. In Trial 1, patients received Dojolvi for 78 weeks. Trial 2 enrolled patients from other trials who were already treated with Dojolvi (including those from Trial 1), as well as patients who were never treated with Dojolvi. Trial 2 is still ongoing and is planned to last up to 5 years. Half of the patients received Dojolvi and half received trioctanoin for 4 months. The benefit of Dojolvi in comparison to trioctanoin was assessed by measuring the changes in heart and muscle function. After 4 months of treatment, patients who received Dojolvi showed similar heart function as patients who received trioctanoin (a different source of calories and fatty acids).

The most common side effects associated with Doljovi are abdominal pain, diarrhea, vomiting, and nausea.

Dojolvi is a liquid that is mixed with meals or snacks four or more times a day.

IMCIVREE (setmelanotide)
Manufacturer: RHYTHM Pharmaceuticals, Inc
Approval Date: November 25, 2020

FDA approved Imcivree to treat obesity and control of hunger associated with pro-opiomelanocortin (POMC) deficiency, a rare disorder that causes severe obesity that begins at an early age.

The approval of Imcivree was based on two clinical trials in which 27 patients with obesity due to specific genetic errors were enrolled. After one year of treatment with Imcivree, 80% of patients with POMC or PCSK1 deficiency and 46% of patients with leptin receptor deficiency achieved at least 10% weight loss.

The most common side effects included injection site reactions, skin darkening, nausea, and headache. More serious effects may include sexual dysfunction, depression, suicidal thoughts, and skin darkening. 

Imcivree is administered subcutaneously once a day and dosage is based on the patient’s weight. 

ISTURISA (osilodrostat) 
Manufacturer: Novartis
Approval Date: March 6, 2020

FDA approved Isturisa to treat adults with Cushing’s disease who either cannot undergo pituitary gland surgery or have undergone the surgery but still have the disease.

The approval of Isturisa was based on a study of 137 adult patients (about three-quarters women) with a mean age of 41 years. The majority of study participants had either undergone pituitary surgery that did not cure Cushing’s disease or were not surgical candidates. In the 24-week, single-arm, open-label period, all patients received a starting dose of 2 mg of Isturisa twice a day that could be increased every 2 weeks up to 30 mg twice a day. 

At the end of the 24-week period, approximately half of patients had cortisol levels within normal limits. After this period, 71 patients who did not need further dose increases and tolerated the drug for the last 12 weeks entered an 8-week, double-blind, randomized withdrawal study where they either received Isturisa or a placebo. At the end of this withdrawal period, 86% of patients receiving Isturisa maintained cortisol levels within normal limits compared to 30% of patients taking the placebo.

The most commonly observed adverse effects included adrenal insufficiency, headache, vomiting, nausea, fatigue, and edema. Hypocortisolism, QTc prolongation, and elevations in adrenal hormone precursors and androgens may also occur in people taking Isturisa.

Isturisa is a tablet taken twice a day orally, approximately every 12 hours. 

NEXLETOL (bempedoic acid)
Manufacturer: Esperion
Approval Date: February 21, 2020

FDA approved Nexletol to treat adults with heterozygous familial hypercholesterolemia (HeFH) or established atherosclerotic cardiovascular disease who require additional lowering of low-density lipoprotein cholesterol (LDL-C).

The approval of Nexletol is based on data published in two clinical trials comprising 3009 patients with high LDL-C and known atherosclerotic cardiovascular disease or HeFH in which it provided an average of 18% placebo-corrected LDL-C lowering when used with moderate or high-intensity statins.

The most common side effects of Nexletol are upper respiratory tract infection, increase in blood levels of uric acid, muscle cramps, back and extremity pain, stomach pain, bronchitis, anemia and elevated liver enzymes. It may cause serious side effects including tendon rupture, and high uric acid levels in the blood.

Nexletol is a tablet taken once daily, in addition to low cholesterol diet and the highest dose of a statin that a patient can tolerate. It should only be taken when LDL cholesterol needs to be lowered further.

OXLUMO (lumasiran)
Manufacturer: Anylam
Approval Date: November 23, 2020

FDA approved Oxlumo for orphan drug designation to treat primary hyperoxaluria type 1 (PH1), a rare genetic disorder.

The approval of Oxlumo is based on data from two studies examining patients with PH1: a randomized, placebo-controlled trial in patients aged 6 years and older and an open-label study in patients younger than 6 years. Patients ranged in age from 4 months to 61 years at
the first dose. 

In the first study, 26 patients received a monthly injection of Oxlumo followed by a maintenance dose every 3 months; 13 patients received placebo injections. The primary end point was the amount of oxalate measured in the urine over 24 hours. In the Oxlumo group, patients had, on average, a 65% reduction of oxalate in the urine, compared to an average 12% reduction in the placebo group. By the sixth month of the study, 52% of patients treated with Oxlumo reached a normal 24-hour urinary oxalate level; no patients treated with the placebo did. 

In the second study, 16 patients younger than 6 years all received Oxlumo. Using another measure of oxalate in the urine, the study showed, on average, a 71% decrease in urinary oxalate by the sixth month of
the study.

Most commonly observed side effects included injection site rejection and abdominal pain. 

Oxlumo is administered via subcutaenous injection by a health care provider.

SOGROYA (somapacitan-beco)
Manufacturer: Novo Nordisk
Approval Date: August 28, 2020

FDA approved Sogroya for replacement of growth hormone in adults with growth hormone deficiency (GHD).

The approval of Sogroya is based on a comprehensive clinical program including the REAL 1 study, a 35-week, double-blind, placebo-controlled study in 300 treatment naïve adult patients or had discontinued other growth hormone formulations for ≥3 months.

Patients were randomized 2:1:2 to receive once-weekly injections of Sogroya or placebo, or daily somatropin for 34 weeks. The primary end point was the change in truncal fat percentage from baseline to week 34. Patients treated with Sogroya demonstrated a mean 1.06% reduction in truncal fat at week 34 compared with an increase 0.47% for placebo (absolute treatment difference of -1.53%; 95% CI: -2.68, -0.38; P=.009). Patients treated with daily somatropin achieved a change in truncal fat percentage of -2.23% after 34 weeks.

Similar improvements in other clinical end points, including normalized insulin-like growth factor standard deviation scores at week 34, were observed in the Sogroya and somatropin treatment arms.

Sogroya’s most common adverse reactions included back pain, arthralgia, dyspepsia, sleep disorder, dizziness, tonsillitis, peripheral edema, vomiting, adrenal insufficiency, hypertension, increased blood creatine phosphokinase, increased weight, and anemia.

Sogroya is a 10 mg/1.5 mL (6.7 mg/mL) injection given subcutaneously once every week.

GASTROENTEROLOGY 

PIZENSY (lactitol)
Manufacturer: Braintree Laboratories, Inc
Approval Date: February 12, 2020

FDA approved Pizensy to treat chronic idiopathic constipation in adults. 

The approval of Pizensy is based on three phase 3 clinical trials in which more than 1400 patients participated in a 6-month, double-blind, placebo-controlled study, a 12-week, blind head-to-head study against lubiprostone, and a 12-month, open-label, chronic use study. Patients who entered the trial had a history of chronic constipation which included having less than three bowel movements per week over the 2-week screening period. Efficacy was assessed using information provided by patients daily in an electronic diary. 

In both pivotal trials, efficacy responders were defined as patients who had at least three complete spontaneous bowel movements (CSBMs) in a given week and an increase of at least one CSBM from baseline in the same week for at least 9 weeks of the 12-week treatment period and at least three of the last 4 weeks (Weeks 9-12).

Over the first 12-week course of treatment, patients treated with Pizensy achieved a significantly greater efficacy response compared with placebo (26% vs 13%; P<.001). This response was sustained in the Pizensy group during Weeks 13 to 24. Over course of treatment, patients who received Pizensy had statistically significant improvements compared with placebo in stool frequency (as measured by the number of spontaneous and complete spontaneous bowel movements per week) and stool consistency (as measured by the Bristol Stool Form Scale).

The most common side effects of Pizensy are upper respiratory infections, gassiness, diarrhea, increased blood creatinine phosphokinase (a type of enzyme), belly distention, and increased blood pressure.

Pizensy is a powder. The content of two packets or bottle caps should be mixed with a beverage and taken once a day. The content of one packet or bottle cap can be taken once a day if the patient develops persistent loose stools with intake of two packets or bottle caps.

GENETIC DISEASES

VILTEPSO (viltolarsen)
Manufacturer: NS Pharma
Approval Date: August 12, 2020

FDA approved Viltepso injection for the treatment of Duchenne muscular dystrophy (DMD) in patients who have a confirmed mutation of the DMD gene that is amenable to exon 53 skipping.

The approval of Viltepso is based on data from two clinical studies with a total of 32 men with genetically confirmed DMD. The increase in dystrophin production was established in one of those two studies, a study that included 16 patients with DMD, with eight patients receiving Viltepso at the recommended dose. In the study, dystrophin levels increased, on average, from 0.6% of normal at baseline to 5.9% of normal at week 25.

The FDA noted that the data demonstrated an increase in dystrophin production that is reasonably likely to predict clinical benefit in patients with DMD who have a confirmed mutation of the dystrophin gene amenable to exon 53 skipping. A clinical benefit of the drug has not been established. In making this decision, the FDA considered the potential risks associated with the drug, the life-threatening and debilitating nature of the disease, and the lack of available therapies. As part of the accelerated approval process, the FDA is requiring the company to conduct a clinical trial to confirm the drug’s clinical benefit. The ongoing study is designed to assess whether Viltepso improves the time to stand for DMD patients with this confirmed mutation. If the trial fails to verify clinical benefit, the FDA may initiate proceedings to withdraw approval of the drug.

Viltepso’s most common side effects are upper respiratory tract infection, injection site reaction, cough, and fever.

The recommended dosage of Viltepso is 80 mg/kg administered once weekly as a 60-minute intravenous infusion. If a dose of Viltepso is missed, it should be administered as soon as possible after the scheduled dose time.

ZOKINVY (lonafarnib)
Manufacturer: Eiger BioPharmaceuticals, Inc
Approval Date: November 20, 2020

FDA approved Zokinvy capsules to reduce the risk of death due to Hutchinson-Gilford progeria syndrome and for the treatment of certain processing-deficient progeroid laminopathies in patients aged one year and older.

The effectiveness of Zokinvy for the treatment of Hutchinson-Gilford progeria syndrome was demonstrated in 62 patients from two single-arm trials that were compared to matched, untreated patients from a separate natural history study. Compared to untreated patients, the lifespan of Hutchinson-Gilford progeria syndrome patients treated with Zokinvy increased by an average of 3 months through the first 3 years of treatment and by an average of 2.5 years through the maximum follow-up time of 11 years. 

Zokinvy’s approval for the treatment of certain processing-deficient progeroid laminopathies that are very rare took into account similarities in the underlying genetic mechanism of disease and other available data.

The most common side effects included nausea, vomiting, diarrhea, infection, decreased appetite, and fatigue.

The recommended starting dosage of Zokinvy for patients with a body surface area (BSA) of 0.39 m² and above is 115 mg/m² twice daily with morning and evening meals, to reduce the risk of gastrointestinal adverse reactions. An appropriate dosage strength of Zokinvy is not available for patients with a BSA of less than 0.39 m².

HEMATOLOGY

BLENREP (belantamab mafodotin-blmf)
Manufacturer: GlaxoSmithKline
Approval Date: August 5, 2020

FDA approved Blenrep to treat multiple myeloma for patients whose cancer returned after, or did not respond to, at least four previous treatments.

Blenrep was approved under FDA’s accelerated approval program, which provides earlier patient access to a promising new drug while the company continues to conduct clinical trials to confirm that the drug works well. In the trial, 30 of 97 patients (31%) treated with Blenrep experienced an improvement in their disease. For 73% of responders that improvement lasted at least 6 months.

Blenrep may cause serious changes to the cornea that can lead to worsening vision and vision loss. Because of the eye problems Blenrep is available only through the Blenrep Risk Evaluation and Mitigation Strategy (REMS). Other serious side effects include low platelet counts, infusion related reactions, and harm to an unborn baby. The most common side effects of Blenrep are corneal changes, decreased vision or blurred vision, nausea, low blood cell counts, fever, infusion-related reactions, fatigue, and changes in kidney or liver function blood tests.

Blenrep is administered intravenously by a heath care professional every 3 weeks. It takes about 30 minutes to receive the Blenrep infusion.

INQOVI (decitabine and cedazuridine)
Manufacturer: Taiho Oncology, Inc
Approval Date: July 7, 2020

FDA approved Inqovi to treat adult patients with myelodysplastic syndromes including chronic myelomonocytic leukemia.

The approval of Inqovi was based on data from a clinical trial in which 18% of patients treated with Inqovi experienced complete response (specific improvements in bone marrow and blood cells) that lasted about 9 months. In Trial 2, 21% of patients treated with Inqovi, experienced complete response that lasted about 7.5 months.

Additionally, about half of the patients who were formerly dependent on transfusions no longer required transfusions during an 8-week period.

Inqovi may cause serious and life-threatening bone marrow suppression. Most common side effects of Inqovi are low cell counts, fatigue, constipation, bleeding, muscle pain, oral pain or sores, joint pain, nausea, shortness of breath, diarrhea, rash, dizziness, febrile neutropenia, swelling of arms or legs, and headache.

Inqovi is a tablet taken once a day on Days 1 through 5 of each 28-day cycle.

ORLADEYO (berotralstat)
Manufacturer: Biocryst Pharmaceuticals
Approval Date: December 4, 2020

FDA approved Orladeyo for prophylaxis to prevent attacks of hereditary angioedema (HAE) in adults and pediatric patients aged 12 years and older.

The approval of Orladeyo is based on data from the phase 3 APeX-2 trial in which Orladeyo significantly reduced attacks at 24 weeks and sustained through 48 weeks. Patients with HAE who completed 48 weeks of treatment (150 mg) saw reductions in their HAE attack rates, from a mean of 2.9 attacks per month at baseline to a mean of 1.0 attacks per month after 48 weeks of therapy. In the long-term, open-label APeX-S trial, patients completing 48 weeks of therapy (150 mg) had a mean attack rate of 0.8 attacks per month.

The most commonly observed adverse effects were abdominal pain, vomiting, diarrhea, back pain, and gastroesophageal reflux disease.

Orladeyo’s recommended dosage is 150 mg once daily. A reduced dosage of 110 mg taken orally once daily with food is recommended in patients with moderate or severe hepatic impairment (Child-Pugh B or C) and in patients taking chronically administered P-glycoprotein or breast cancer resistance protein inhibitors (eg, cyclosporine).

INFECTIOUS DISEASES

ARTESUNATE (artesunate)
Manufacturer: Amivas
Approval Date: May 26, 2020

FDA approved Artesunate to treat severe malaria in adult and pediatric patients.

The approval of Artesunate was evaluated in a randomized controlled trial in Asia (Trial 1) and a supportive published randomized controlled trial in Africa (Trial 2). Trial 1 enrolled 1461 patients who received either intravenous (IV) artesunate or the comparator drug quinine and included 202 pediatric patients younger than 15 years. Trial 2 included 5425 randomized pediatric patients younger than 15 years of age with severe malaria who were treated with artesunate or quinine. In both trials, the number of patients treated with artesunate who died in the hospital was significantly lower than the number who died in the control group treated with quinine. In Trial 1, the most common adverse reactions in patients with malaria treated with IV artesunate were acute renal failure requiring dialysis, hemoglobinuria, and jaundice. The safety profile in Trial 2 was generally similar to Trial 1. Artesunate should not be used in patients with known serious allergy to artesunate such as anaphylaxis.

Artesunate is administered via injection. Treatment of severe malaria with IV artesunate should always be followed by a complete treatment course of an appropriate oral antimalarial regimen.

INMAZEB (atoltivimab, maftivimab, and odesivimab-ebgn)
Manufacturer: Regeneron
Approval Date: October 14, 2020

FDA approved Inmazeb, a mixture of three monoclonal antibodies, as the first FDA-approved treatment for Zaire ebolavirus (Ebola virus) infection in adult and pediatric patients. 

The approval of Inmazeb was based on the evaluation of 382 adult and pediatric patients with confirmed Zaire ebolavirus infection in one clinical trial (the PALM trial) and as part of an expanded access program conducted in the Democratic Republic of the Congo (DRC) during an Ebola virus outbreak in 2018-2019. The PALM trial was led by the US National Institutes of Health and the DRC’s Institut National de Recherche Biomédicale with contributions from several other international organizations and agencies.

In the trial, 154 patients received Inmazeb (50 mg of each monoclonal antibody) intravenously as a single infusion, and 168 patients received an investigational control. The primary efficacy endpoint was 28-day mortality. The primary analysis population included all patients who were randomized and concurrently eligible to receive either Inmazeb or the investigational control during the same period of the trial. Of the 154 patients who received Inmazeb, 33.8% died after 28 days, compared to 51% of the 153 patients who received a control. In the expanded access program, an additional 228 patients received Inmazeb.

The most common side effects of Inmazeb are fever, chills, fast heart rate, fast breathing and vomiting. It may cause serious side effects including severe and life-threatening allergic reactions during and after the infusion.

Inmazeb is administered via intravenous infusion by a health care provider. Dosage is based on the patient’s weight.

LAMPIT (nifurtimox)
Manufacturer: Bayer HealthCare Pharmaceuticals Inc
Approval Date: August 6, 2020

FDA approved Lampit to treat Chagas disease in certain pediatric patients younger than 18 years. 

The approval of Lampit was based on evidence from a prospective, randomized, double-blind evaluation in 330 children with Chagas disease. The study was conducted at 25 investigational sites in Argentina, Bolivia, and Colombia between 2016 and 2018.7 In the study, 330 pediatric patients with serologic evidence of Trypanosoma cruzi infection (without Chagas disease-related cardiovascular and/or gastrointestinal symptoms) were randomly assigned 2:1 to receive either a 60-day (n=219) or a 30-day (n=111) Lampit treatment regimen, and were followed up for one year after end of treatment. The results showed superiority in favor of the Lampit 60-day arm compared to the Lampit 30-day arm (not an approved dosing regimen).

Common side effects of Lampit are vomiting, abdominal pain, headache, decreased appetite, nausea, fever, and rash. Lampit can also cause serious reactions including worsening of neurologic and mental conditions, severe allergic reactions, weight loss, and possible harm to the developing fetus.

Lampit is administered as tablet taken orally 3 times a day with food for 60 days. Total daily dose is determined by the child’s weight.

RUKOBIA (fostemsavir)
Manufacturer: ViiV Healthcare
Approval Date: July 2, 2020

FDA approved Rukobia, a new type of antiretroviral medication for adults living with HIV who have tried multiple HIV medications and whose HIV infection cannot be successfully treated with other therapies because of resistance, intolerance or safety considerations.

The approval of Rukobia was based on a clinical trial of 371 heavily treatment-experienced adult participants who continued to have high levels of virus (HIV-RNA) in their blood despite being on antiretroviral drugs. The main trial arm included 272 patients and an additional 99 participants received Rukobia in a different arm of the trial. Most participants had been treated for HIV for more than 15 years (71%), had been exposed to five or more different HIV treatment regimens before entering the trial (85%) and/or had a history of AIDS (86%). Participants in the main trial cohort received either Rukobia or a placebo twice daily for 8 days, in addition to their failing antiretroviral regimen. On the eighth day, participants treated with Rukobia had a significantly greater decrease in levels of HIV-RNA in their blood compared to those taking the placebo. After the eighth day, all participants received Rukobia with other antiretroviral drugs. After 24 weeks of Rukobia plus other antiretroviral drugs, 53% of participants achieved HIV RNA suppression, where levels of HIV were low enough to be considered undetectable. After 96 weeks, 60% of participants continued to have HIV RNA suppression.

The most common adverse reaction to Rukobia was nausea. Severe adverse reactions included elevations in liver enzymes among participants also infected with hepatitis B or C virus, and changes in the immune system (immune reconstitution syndrome).

The recommended dosage of Rukobia is one 600-mg tablet taken orally twice daily with or without food.

NEUROLOGY 

ENSPRYNG (satralizumab-mwge)
Manufacturer: Genentech, Inc
Approval Date: August 14, 2020

FDA approved Enspryng for the treatment of neuromyelitis optica spectrum disorder (NMOSD) in adults with a particular antibody—patients who are anti-aquaporin-4 or AQP4 antibody-positive.

The approval for Enspryng was based on results of two 96-week clinical studies. The first study included 95 adult patients; 64 of these patients had antibodies against AQP4 (anti-AQP4 positive). During this study, treatment with Enspryng reduced the number of NMOSD relapses by 74% in patients who were anti-AQP4 positive compared to treatment with a placebo.

The second study included 76 adult patients; 52 of these patients were anti-AQP4 positive. During the second study, treatment with Enspryng reduced the number of relapses in patients who were anti-AQP4 positive by 78% compared to treatment with a placebo. There was no evidence of a benefit in patients who were anti-AQP4 antibody negative in either trial.

The most common side effects for Enspryng are nasopharyngitis, headache, upper respiratory tract infection, inflammation of the lining of the stomach, rash, joint pain, extremity pain, fatigue and nausea. The prescribing information for Enspryng includes a warning for increased risk of infection, including serious and potentially fatal infections—such as potential reactivation of hepatitis B and tuberculosis. Other warnings and precautions for Enspryng include elevated liver enzymes, decreased neutrophil counts and hypersensitivity reactions

The recommended loading dosage of Enspryng for the first three administrations is 120 mg subcutaneously at Weeks 0, 2, and 4, followed by a maintenance dosage of 120 mg every 4 weeks.

EVRYSDI (risdiplam)
Manufacturer: Genentech Inc.
Approval Date: August 7, 2020

FDA approved Evrysdi to treat spinal muscular atrophy (SMA), a rare and often fatal genetic disease affecting muscle strength and movement, in patients aged 2 months and older. 

The approval of Evrysdi was based on two safety and efficacy clinical trials. The infantile-onset SMA study included 21 patients who had an average age of 6.7 months when the study began. In that open-label study, efficacy was established based on the ability to sit without support for at least five seconds and survival without permanent ventilation. After 12 months of treatment, 41% of patients were able to sit independently for more than five seconds, a meaningful difference from the natural progression of the disease because almost all untreated infants with infantile-onset SMA cannot sit independently. After 23 or more months of treatment, 81% of patients were alive without permanent ventilation, which is a noticeable improvement from typical disease progression without treatment.

Patients with later-onset SMA were evaluated in a second randomized, placebo-controlled study. The study included 180 patients with SMA aged 2 to 25 years. The primary end point was change from baseline in MFM32 (a test of motor function) total score at the one-year mark. Patients on Evrysdi saw an average 1.36 increase in their score at the one-year mark compared to a 0.19 decrease in patients on placebo.

The most common side effects of Evrysdi include fever, diarrhea, rash, ulcers of the mouth area, arthralgia, and urinary tract infections. 

Evrysdi is taken as a liquid by morally once daily after a meal. The amount of liquid is determined by the patient’s weight.

NURTEC ODT (rimegepant)
Manufacturer: Biohaven Pharmaceutical Inc.
Approval Date: February 27, 2020

FDA approved Nurtec ODT for treatment of acute migraine with or without aura in adults.

The approval of Nurtec ODT was based on efficacy data from a randomized, double-blind, placebo-controlled phase 3 trial that compared Nurtec ODT with placebo in 1466 adult patients for the acute treatment of migraine with and without aura. Patients were randomized to receive Nurtec ODT 75mg once (n=732) or placebo (n=734). The primary end point was pain freedom and most bothersome symptom (MBS) freedom at 2 hours after dosing in patients who treated a migraine with moderate to severe pain.

Results demonstrated that a statistically significantly greater proportion of patients treated with Nurtec ODT achieved headache pain freedom (21.2% vs 10.9%; P<.001) and MBS freedom (35.1% vs 26.8%; P=.001) 2 hours after a single dose compared with placebo, respectively.

The most common side effect observed is nausea but it could also cause severe allergic reaction.

Nurtec ODT is a tablet taken orally once daily, as needed, not to exceed 75 mg/day.

ONGENTYS (opicapone)
Manufacturer: Neurocrine Biosciences, Inc
Approval Date: April 24, 2020

FDA approved Ongentys to treat patients with Parkinson disease experiencing “off” episodes while taking drugs (levodopa and carbidopa)

The FDA approval of Ongentys is supported by data from 38 clinical studies, including two multinational phase 3 clinical studies (BIPARK-1 and BIPARK-2), with more than 1000 patients with Parkinson disease treated with Ongentys. In the BIPARK-1 trial, approximately 600 patients with Parkinson disease and motor fluctuations received one of three doses of Ongentys (5 mg, 25 mg, or 50 mg), placebo or 200 mg doses of the COMT inhibitor entacapone for 14 or 15 weeks. In the BIPARK-2 trial, approximately 400 patients received one of two doses of Ongentys (25 mg or 50 mg) or placebo for 14 or 15 weeks. Both studies included a one-year open-label extension. Data from both trials showed that Ongentys 50 mg significantly reduced “off” time from baseline to week 14 or 15 compared to placebo. “On” time without troublesome dyskinesia also increased from baseline to week 14 or 15 compared to placebo.

The most common side effects are uncontrolled movements, constipation, increase in blood creatinine level, fainting, and weight decrease. More serious side effects could include heart rate and blood pressure changes when used with certain medicines, falling asleep during normal activities, low blood pressure and fainting, dyskinesia, and unusual urges.

Ongentys is a capsule, 25 mg or 50 mg, taken orally once daily at bedtime, in addition to drugs for the treatment of Parkinson disease (levodopa and carbidopa).

UPLIZNA (inebilizumab-cdon)
Manufacturer: Viela Bio, Inc
Approval Date: June 11, 2020

FDA approved Uplizna injection for intravenous use for the treatment of neuromyelitis optica spectrum disorder (NMOSD) in adult patients with a particular antibody (patients who are anti-aquaporin-4 or AQP4 antibody positive).

The approval of Uplizana is based on its demonstrated effectiveness in a clinical study of 230 adult patients. In the trial, 213 of the 230 patients had antibodies against AQP4 (anti-AQP4 antibody positive). During the 197-day study, the risk of an NMOSD relapse in the 161 anti-AQP4 antibody positive patients who were treated with Uplizna was reduced by 77% when compared to the placebo treatment group. There was no evidence of a benefit in patients who were anti-AQP4 antibody negative.

The most common side effects are urinary tract infection and joint pain. More serious side effects could include infusion reactions, infections, and a harm to un unborn baby.

Uplizna is administered via intravenous infusion over 90 minutes by a health care provider. First two infusions are given 2 weeks apart followed by one infusion every 6 months.

VYEPTI (eptinezumab-jjmr)
Manufacturer: Lundbeck
Approval Date: February 21, 2020

FDA approved Vyepti for the preventive treatment of migraine in adults.

The approval of Vyepti is based on evidence from two clinical trials of 1741 patients with chronic or episodic migraine headaches. Patients were assigned to receive one of two doses of Vyepti or placebo injections every 3 months for a total of 12 months in Trial 1, and for a total of 6 months in Trial 2. 

In PROMISE-1, a total of 665 patients with episodic migraine were randomized to receive placebo, 100-mg eptinezumab, or 300-mg eptinezumab every 3 months for 12 months. The mean migraine frequency at baseline was approximately 8.6 migraine days each month. The results indicated that the mean reduction in migraine days from baseline to placebo was -3.9 days for 100 mg, -4.3 days for 300 mg, and -3.2 days for placebo. 

In PROMISE-2, a total of 1072 patients with chronic migraine were randomized to receive placebo, 100-mg eptinezumab, or 300-mg eptinezumab every 3 months for 6 months. The mean migraine frequency at baseline was approximately 16.1 migraine days per month. The results indicated that the mean reduction in migraine days from baseline to placebo was -7.7 days for 100 mg, -8.2 days for 300 mg, and -5.6 days for placebo.

The most common side effects of Vyepti are stuffy nose and nasopharyngitis and allergic reactions.

Vyepti is administered via a 30-minute intravenous infusion by a health care provider every 3 months. The recommended dose is 100 mg every 3 months; some patients may benefit from a dose of 300 mg.

ZEPOSIA (ozanimod)
Manufacturer: Celgene Corporation
Approval Date: March 25, 2020

FDA approved Zeposia to treat relapsing forms of multiple sclerosis in adults, including clinically isolating syndrome, relapsing-remitting disease, and active secondary progressive disease.

The approval of Zeposia was based on evidence from two randomized, double-blind, double-dummy, active comparator-controlled clinical trials of similar design. Both trials included patients with relapsing forms of multiple sclerosis. Patients were randomized to receive either Zeposia 0.92 mg or 0.46 mg given orally once daily, beginning with a dose titration or interferon beta-1a, 30 mcg given intramuscularly once weekly. Patients in Trial 1 were treated until the last enrolled patient completed 1 year of treatment and patients in Trial 2 were treated for 2 years. The primary end point was the annualized relapse rate (ARR) during the treatment period. Zeposia demonstrated a relative reduction in ARR vs AVONEX of 48% through one year in the SUNBEAM study and 38% at 2 years in the RADIANCE study (absolute ARR of 0.18 vs 0.35 and 0.17 vs 0.28, respectively)

The most common side effects of Zeposia are upper respiratory infections, increased liver enzymes, blood pressure drop upon standing, urinary tract infection, back pain, and high blood pressure. More serious side effects may include life-threatening infections, decreased heart rate, liver injury, increased blood pressure, decreased lung function, and macular edema.

Zeposia is a capsule taken by orally once daily. Zeposia is initially started at a low dose and then slowly increased over the first week.

KOSELUGO (selumetinib)
Manufacturer: AstraZeneca
Approval Date: April 10, 2020

FDA approved Koselugo to treat neurofibromatosis type 1 (NF1), a genetic disorder of the nervous system causing tumors to grow on nerves for pediatric patients aged 2 years and older.

The approval of Koselugo is based on results from a trial of patients with NF1 whose PN(s) were causing significant symptoms and could not be surgically removed. The enrolled patients received Koselugo capsule twice daily until disease progression or unacceptable toxicity.

In the trial, 33 of 50 patients (66%) who received Koselugo experienced partial tumor shrinkage. Of these patients, 82% had a tumor shrinkage lasting 12 months or longer.

The most common side effects of Koselugo are vomiting, rash, abdominal pain, diarrhea, nausea, dry skin, fatigue, muscle and bone pain, fever, acne, mouth sores, headache, nail infection, and itching.

Koselugo is administered in tablet form, taken orally, 25 mg/m² twice daily, given on an empty stomach.

Find approval listings for oncology, ophthalmology, pain management, and procedural medicine in part 2 here.