New FDA Drug Approvals in 2019 by Indication: Part 1

First Report Managed Care's December issue includes a guide to 2019 FDA Drug Approvals by indication. Find Part 2 here. 

CARDIOLOGY

VYNDAQEL (tafamidis meglumine)
Manufacturer: FoldRx
Approval Date: May 3, 2019

FDA approved Vyndaqel and Vyndamax capsules for the treatment of cardiomyopathy caused by transthyretin mediated amyloidosis in adults. 

Vyndaqel and Vyndamax contain the same active moiety but are not substitutable on a milligram to milligram basis and therefore have different recommended doses. 

The approval of Vyndaqel and Vyndamax was based on the results of a randomized clinical trial of 441 patients that showed a higher survival rate after an average of 30 months. Vyndaqel also proved to reduce the number of hospitalizations for cardiovascular problems. 

In patients with the cardiomyopathy of transthyretin amyloidosis, a fibrous substance called amyloid is deposited in the heart where it interferes with the heart’s function. The condition is progressive and may cause death.

No drug-associated side effects were identified in the patient group. Tafamidis may cause fetal harm when administered to a pregnant woman. Women taking Vyndaqel or Vyndamax should discuss pregnancy planning and prevention with their health care professional.

Vyndaqel and Vyndamax capsules should be taken once a day by mouth. 

DERMATOLOGY

AKLIEF Cream 0.005% (trifarotene)
Manufacturer: Galderma
Approval Date: October 4, 2019

FDA approved Aklief Cream, 0.005% for the topical treatment of acne vulgaris in patients aged 9 years and older. Acne vulgaris is a skin disease characterized by blackheads, whiteheads, pimples, and sometimes oily skin and scarring.

The FDA approval of Aklief Cream is based on results from two identical phase 3, randomized multicenter, parallel group, double-blind, vehicle-controlled clinical trials. With use of once-daily Aklief Cream in patients with moderate acne on the face and trunk, 2420 patients showed significantly reduced inflammatory lesions as early as 2 weeks on the face and 4 weeks on the back, shoulders and chest compared to vehicle (P<0.05).

Aklief Cream was well tolerated when used on the face, back, shoulders, and chest. The most common adverse reactions (incidence >1%) included application site irritation, application site pruritus (itching) and sunburn.

Aklief Cream is provided in a 45-g pump and applied to the affected skin of face and/or trunk once a day, in the evening.

SKYRIZI (risankizumab-rzaa)
Manufacturer: AbbVie Inc
Approval Date: April 23, 2019

FDA approved Skyrizi, an IL-23 inhibitor, for the treatment of moderate to severe plaque psoriasis in adults who may benefit from taking injections or pills (systemic therapy) or phototherapy (treatment using UV light).

The FDA approval of Skyrizi was based on evidence from five clinical trials of 1606 patients with moderate to severe plaque psoriasis in Asia, Canada, Europe, Mexico, South America, and the United States.

The approval is supported by results of AbbVie’s global phase 3 psoriasis program, which assessed the safety and efficacy in adults with moderate to severe plaque psoriasis across four randomized, placebo and/or active-controlled pivotal studies: ultIMMa-1, ultIMMa-2, IMMhance and IMMvent. The co-primary endpoints of these studies were Psoriasis Area and Severity Index (PASI 90) and static Physician Global Assessment {sPGA) score of clear or almost clear {sPGA 0/1) at 16 weeks vs placebo. 

In ultIMMa-1 and ultIMMa-2 at 16 weeks, PASI 90 was achieved in 75% of people treated with Skyrizi, compared to 5% and 2% receiving placebo, respectively (P<0.001). PASI 100 was achieved in 36% and 51% of people treated with Skyrizi, compared to 0% and 2% receiving placebo, respectively (P<0.001).

Skyrizi may lower the immune system’s ability to fight infections and may increase the risk of infections. The most common side effects include upper respiratory infections, headache, tiredness, injection site reactions, and fungal infections. Before starting injections, patients should be assessed for tuberculosis infection. 

Skyrizi is given as two injections subcutaneously, 4 weeks apart for the initial two doses and then once every 12 weeks. It can be administered in-office or via self-injection after training. 

JEUVEAU (prabotulinumtoxinA-xvfs)
Manufacturer: Evolus
Approval Date: February 1, 2019

FDA approved Jeuveau, acetylcholine release inhibitor and a neuromuscular blocking agent, for the temporary improvement in the appearance of moderate to severe glabellar lines associated with corrugator and/or procerus muscle activity in adults.

The FDA approved Jeuveau based on clinical data from two US phase 3 randomized, multi-center, double-blind, placebo-controlled clinical trials both of which met the primary endpoint and demonstrated efficacy compared with placebo in the reduction of the severity of glabellar lines, defined as a 2-point composite improvement agreed upon by physician and patient, at day 30. Data showed 67.5% of participants in study one (EV-001) and 70.4% of participants in study two (EV-002) met the primary endpoint, compared to 1.2% and 1.3% of patients in each placebo arm respectively.

The most common side effects of Jeuveau include allergic reactions (itching, rash, hives, wheezing, trouble breathing), eye problems
(dry eye, reduced blinking, and corneal problems), headache, eyelid dropping, upper respiratory infection, and increased white blood cell count. More severe side effects could include heart problems, such as irregular heartbeat and/or heart attacks in patients that have botulinum toxin sensitivities. 

Jeuveau is a proprietary 900 kDa purified botulinum toxin type A formulation injected directly into affected muscle by a health care provider once every 3 months as needed. 

GASTROENTEROLOGY

IBSRELA (tenapanor)
Manufacturer: Ardelyx
Approval Date: September 12, 2019

FDA approved Ibsrela, an NHE3 sodium transport inhibitor, as treatment for adults with irritable bowel syndrome with constipation (IBS-C).

FDA approval for Ibsrela is supported by evidence from two phase 3 trials that showed a significant reduction in constipation and abdominal pain in adult patients with IBS-C. The trials included 1199 patients, aged 18 to 75 years, at 214 sites in the United States.

In each trial, patients were randomly assigned to receive either IBSRELA or placebo twice daily for at least 12 weeks. Neither the patients nor the health care providers knew which treatment was being given. After these 12 weeks of treatment, patients in Trial 1 continued same trial design for an additional 14 weeks, and patients in Trial 2 entered a different trial design called Randomized Withdrawal for 4 weeks where some patients continued to receive Ibsrela, and others were switched to placebo, in a blinded fashion.

In both trials, patients used diaries to record the degree of abdominal pain and stool frequency. The benefit of Ibsrela was assessed by improvements in abdominal pain and complete spontaneous bowel movements in comparison to placebo.

In both phase 3 IBS-C trials, Ibsreala met the primary endpoint as compared with placebo (Trial 1: 37% versus 24%, Ibsrela vs placebo, respectively. Trial 2 showed 27% vs 19% Ibserela vs placebo, respectively).

In the two IBS-C trials, the most common adverse reaction in Ibsrela-treated patients (incidence ≥2% and greater than in the placebo group) was diarrhea (Trial 1: 16% Ibsrela vs 4% placebo; Trial 2: 15% Ibsrela vs 2% placebo). 

The most common side effects of Ibsrela are diarrhea, which sometimes may be severe, abdominal distension, excessive gas and dizziness.

Ibsrela is a 50mg tablet taken orally twice daily

GENETIC DISEASES

SCENESSE (afamelanotide)
Manufacturer: Clinuvel Pharmaceuticals 
Approval Date: October 8, 2019

FDA approved Scenesse to increase pain-free light exposure in adult patients with a history of phototoxic reactions from erythropoietic protoporphyria (EPP), a rare, inherited disease that generally starts early in life. Among other characteristics, patients with this disease have painful phototoxic episodes which lead to light avoidance and chronic skin changes. 

The FDA approval of Scenesse was based on evidence from three clinical trials of 244 adult patients aged 18 to 74 years with EPP, conducted at 22 sites in United States and Europe. Over 180 days, patients who received the Scenesse implant spent more time (about 64 hours) in direct sunlight with no pain in comparison to patients who received placebo (about 41 hours).

During Trial 1, patients received Scenesse or vehicle implant every 2 months and were followed for 180 days. Every day, patients recorded the number of hours spent in direct sunlight between 10 am and 6 pm and whether they experienced any phototoxic pain.  In Trial 2, for 270 days, patients with Scenesse implants recorded daily the number of hours spent outdoors whether “most of the day” was spent in direct sunlight, shade, or a combination of both, and whether they experienced any phototoxic pain that day. The trial measured the total number of hours over 270 days spent outdoors between 10 am and 3 pm on days with no pain for which “most of the day” was spent in direct sunlight. The third trial randomized patients to receive three Scenesse implants every 2 months and followed for 180 to monitor sides effects.

The most common side effects of Scenesse are implant site reaction, nausea, throat pain, cough, fatigue, dizziness, skin darkening, sleepiness, mole (melanocytic nevus), respiratory tract infection, sleepiness, nonacute porphyria, and skin irritation. Because of skin darkening (including darkening of moles and freckles), a regular skin examination is recommended.

Scenesse is an implant administered subcutaneously every 2 months by a health care professional.

HEMATOLOGY

OXBRYTA (voxelotor)
Manufacturer: Global Blood Therapeutics
Approval Date: November 25, 2019

FDA approved Oxbryta for the treatment of sickle cell disease (SCD) in adults and pediatric patients aged 12 years and older.

The FDA approval of Oxbryta is supported by results from a clinical trial with 274 patients with SCD. During the trial, 90 patients received 1500mg of Oxbryta, 92 patients received 900mg of Oxbryta, and 92 patients received a placebo. The effectiveness was measured by examining hemoglobin response rate. Patients in the 1500mg group experienced a 51.1% hemoglobin response rate increase, compared to 6.5% in the placebo group. 

Common side effects for patients taking Oxbryta were headache, diarrhea, abdominal pain, nausea, fatigue, rash and pyrexia (fever).

Oxbryta is a tablet taken orally. Oxbryta was granted accelerated approval but further clinical trials are required to verify and describe Oxbryta’s clinical benefit.

GIVLAARI (givosiran)
Manufacturer: Alnylam
Approval Date: November 20, 2019

FDA approved Givlaari for the treatment of adult patients with acute hepatic porphyria, a genetic disorder resulting in the buildup of toxic porphyrin molecules which are formed during the production of heme (which helps bind oxygen in the blood).

The FDA approval of Givlaari is supported by results from a clinical trial of 94 patients with acute hepatic porphyria. In the trial, patients received either Givlaari or a placebo. Patients who received Givlaari experienced fewer porphyria attacks (about 1.9 attacks) in a 6-month period, compared to patients who received placebo (about 6.5 attacks). Overall, patients taking Givlaari experienced 70% fewer porphyria attacks compared with patients taking a placebo.

The most common adverse effects of Givlaari include life-threatening allergic reactions, serious liver and kidney injury, injection site reactions, and nausea. Health care professionals should monitor patients for signs of allergic reaction and renal function. Patients should also have their liver function tested before and periodically during treatment.

Givlaari is administered via an injection subcutaneously by a health care professional once a month. 

ADAKVEO (crizanlizumab-tmca)
Manufacturer: Novartis Pharmaceuticals Corporation
Approval Date: November 15, 2019

FDA approved Adakveo infusion as a treatment to reduce the frequency of vaso-occlusive crisis (VOC), a common and painful complication of sickle cell disease that occurs when blood circulation is obstructed by sickled red blood cells, for patients aged 16 years and older.

The FDA approval of Adakveo is supported by a randomized clinical trial where 198 patients with sickle cell disease with a history of
VOC received either Adakeveo or a placebo for 52 weeks. The first two infusions were given 2 weeks apart, then every 4 weeks for a year. Patients and health care providers did not know which treatment had been given until the end of the trial. Benefits of Adakveo were measured by assessing the number of VOC health care visits that required pain treatments. Overall, the patients treated with Adakveo experienced fewer health care visits for VOC annually (median annual rate of 1.63 visits), compared to patients who received a placebo (median annual rate of 2.98 visits). 

In addition, 36% of patients who received Adakveo did not experience VOC during the study, and it delayed the time that patients first experienced VOC after starting treatment from 1.4 months to 4.1 months.

The common side effects experienced by those taking Adakveo include back pain, nausea, fever, and joint pain. Health care professionals should monitor patients for infusion-related reactions, interference with automated platelet counts or platelet clumping, and run tests as soon as possible or use citrate tubes (a practice to avoid platelet activation).

Adakveo is administered by a health care professional via intravenous infusion over 30 minutes. The first two infusions are given 2 weeks apart and then every 4 weeks. 

REBLOZYL (luspatercept–aamt)
Manufacturer: Celgene Corporation
Approval Date: November 8, 2019

FDA approved Reblozyl for the treatment of anemia in adult patients with beta thalassemia who require regular red blood cell (RBC) transfusions.

The FDA approval of Reblozyl is based on the results of a clinical trial comprised of 336 patients with beta thalassemia who required RBC transfusions. During the trial 112 patients received a placebo. Of those who received Reblozyl, 21% saw at least a 33% reduction in transfusions, compared with the 4.5% of placebo patients. This reduction in transfusions mean that patients required fewer transfusions while taking Reblozyl. 

The most common side effects of Reblozyl are headache, bone pain and joint arthralgia, fatigue, cough, abdominal pain, diarrhea, and dizziness.

Reblozyl is a subcutaneous injection administered every 3 weeks. 

ACCRUFER (ferric maltol)
Manufacturer: Shield Therapeutics
Approval Date: July 25, 2019

FDA approved Accufer, an oral nonsalt replacement product, to treat iron deficiency anemia in adults. 

The FDA approval of Accrufer was based on three clinical trials where patients with low iron stores and consequent iron deficiency anemia. The first two trials comprised patients with iron deficiency caused by inflammatory bowel disease, and in the third, by chronic kidney disease. 

In the first two studies, patients were randomized to receive Accrufer or a placebo for 12 weeks. The major efficacy outcome was the mean difference in hemoglobin (Hb)

concentration from baseline to week 12 between Accrufer and placebo. The least square mean difference in the change from baseline in Hb concentration between Accrufer and placebo was 2.18 g/dL (P < 0.0001).

In the second study, patients were randomized to receive either Accrufer or placebo for 16 weeks. The major efficacy outcome was the mean difference in Hb concentration from baseline to week 16 between Accrufer and placebo. The LS mean difference in the change from baseline in Hb concentration between Accrufer and placebo was 0.52 g/dL (P = 0.0149).

The most common side effects of Accrufer are gas, diarrhea, constipation, stool color change, nausea, vomiting, and abdominal discomfort, bloating and pain.

The recommended dosage of Accrufer is 30 mg twice daily, taken 1 hour before or 2 hours after a meal.

CABLIVI (caplacizumab-yhdp)
Manufacturer: Ablynx NV
Approval Date: February 6, 2019

FDA approved Cablivi injection, the first therapy specifically indicated, in combination with plasma exchange and immunosuppressive therapy, for the treatment of adult patients with acquired thrombotic thrombocytopenic purpura (aTTP), a rare and life-threatening disorder that causes blood clotting.

The FDA approval of Cablivi is based on the measured efficacy from a clinical trial comprising 145 patients who were randomly assigned to receive Cablivia or placebo while receiving the current standard of plasma exchange and immunosuppressive therapy. The results of the trial demonstrated that platelet counts improved faster among patients treated with Cablivi compared to placebo. Treatment with Cablivi also resulted in a lower total number of patients with either aTTP-related death and reoccurrence of aTTP during the treatment period, or at least one treatment-emergent major thrombotic event. The proportion of patients with a reoccrance of aTTP throughout the whole study period was lower in the Cablivi group vs the placebo, 13% vs 38%, respectively. 

Common side effects reported by clinical trial patients included bleeding of the nose or gums, and headache. Due to this, the prescribing information for Cablivi includes a warning to advise health care professionals and patients to communicate the risk of severe bleeding. 

Cablivi injections are used in combination with standard treatment of plasma exchange and medications that suppresses the immune system. The first dosage is administered by a health care professional intravenously at least 15 minutes before the first plasma exchange. Following doses can be administered subcutaneously after daily plasma exchanged and for 30 days after plasma exchange is stopped. 

IMMUNOLOGY

RINVOQ (upadacitinib)
Manufacturer: AbbVie Inc
Approval Date: August 16, 2019

FDA approved Rinvoq tablets to treat adult patients with moderately to severely active rheumatoid arthritis (RA) in whom methotrexate (MTX) did not work well or could not be tolerated.

The FDA approval of Rinvoq is supported by efficacy and safety data from five clinical trials with 3141 patients with active RA. These five trials are part of the SELECT program, one of the largest phase 3 programs in RA. 

Across the SELECT phase 3 studies, Rinvoq met all primary and ranked secondary endpoints. The primary endpoints include:

• In SELECT-EARLY, 52% of MTX-naïve patients treated with Rinvoq 15 mg achieved American College of Rheumatology 50% improvement (ACR50) vs 28% treated with MTX at week 12
• In SELECT-MONOTHERAPY, 68% of MTX-IR patients treated with Rinvoq 15 mg achieved ACR20 vs 41% treated with continued MTX at week 14
• In SELECT-COMPARE, 71% of MTX-IR patients treated with Rinvoq 15 mg plus MTX achieved ACR20 vs 36% treated with placebo plus MTX at week 12
• In SELECT-NEXT, 64% of csDMARD-IR patients treated with Rinvoq 15 mg plus csDMARDs achieved ACR20 vs 36% treated with placebo plus csDMARDs at week 12
• In SELECT-BEYOND, 65% of biologic-IR patients treated with Rinvoq 15 mg plus csDMARDs achieved ACR20 vs 28% treated with placebo plus csDMARDs at week 12

Rinvoq may cause serious side effects including life-threatening infections that may lead to hospitalization or death, increased risk of lymphoma  (immune system cancer) and some other cancers, and blood clots in the veins and arteries. Other serious side effects include tears in the stomach or intestines, low blood cell counts, abnormal liver tests, harm to a fetus, and increased cholesterol. The most common side effects are upper respiratory infections, nausea, cough, and fever.

Rinvoq is a tablet taken orally once daily.

INFECTIOUS DISEASES

FETROJA (cefiderocol)
Manufacturer: Shionogi & Co, Ltd
Approval Date: November 14, 2019

FDA approved Fetroja, an antibacterial drug, to treat patients with complicated urinary tract infections who have limited or no alternative treatment options.

The FDA approval of Fetroja was based on studies of 448 patients with complicated urinary tract infections. Of the patients who were administered Fetroja, 72.6% had resolution of symptoms and eradication of the bacteria approximately 7 days after completing treatment compared with 54.6% in patients who received an alternative antibiotic. The clinical response rates were similar between the two treatment groups.

Labeling for Fetroja includes a warning regarding the higher all-cause mortality rate observed in Fetroja-treated patients compared to those treated with other antibiotics in a trial in critically ill patients with multidrug-resistant gram-negative bacterial infections. The cause of the increase in mortality has not been established. 

The most common adverse reactions observed in patients treated with Fetroja included diarrhea, constipation, nausea, vomiting, elevations in liver tests, rash, infusion site reactions, candidiasis, cough, headache, and hypokalemia. Fetroja should not be used in individuals with a known history of severe hypersensitivity to ß-lactam antibacterial drugs.

Fetroja infusions are administered by a health care professional intravenously every 8 hours.

XENLETA (lefamulin)
Manufacturer: NABRIVA Therapeutics, Inc
Approval Date: August 19, 2019

FDA approved Xenleta, an antibacterial medicine, to treat adults with community-acquired bacterial pneumonia (CABD).

The FDA approval of Xenleta was evaluated in two clinical trials with a total of 1289 patients with CABD, between the ages 18 and 97 years old. In these trials, treatment with Xenleta was compared to another antibiotic, moxifloxacin with or without linezolid. Half the trial patients received Xenleta and half received the comparator. The trials showed that patients treated with Xenleta had similar rates of clinical success as those treated with moxifloxacin with or without linezolid.

Xenleta may cause serious side effects including changes in the heart rhythm, diarrhea caused by Clostridium difficile, and harm to an unborn baby. The most common side effects are diarrhea, nausea, injection site reactions, liver enzyme elevation, and vomiting.

Xenleta can either be administered by a health care professional as an intravenous infusion of 150mg over 60 minutes, twice daily for 5 to 7 days (with patients eventually switching to tablets to complete treatment) or taken as a 600mg tablet every 12 hours for 5 days. 

RECARBRIO (imipenem, cilastatin and relebactam)
Manufacturer: Merck Sharp & Dohme Corp.
Approval Date: July 16, 2019

FDA approved Recarbrio, an antibacterial drug, to treat complicated urinary tract infections (cUTI) and complicated intra-abdominal infections (cIAI).

The FDA approval of Recarbrio is part of a three-drug combination injection containing imipenem-cilastatin, a previously FDA-approved antibiotic, and relebactam, a new ß-lactamase inhibitor. The latest approval is based on findings from a study evaluating the efficacy and safety of imipenem-cilastatin for the treatment of cUTI and cIAI. The safety of Recarbrio, administered via injection, was studied in two trials, one each for cUTI and cIAI. The cUTI trial included 298
adult patients with 99 treated with the proposed dose of Recarbrio. The cIAI trial included 347 patients with 117 treated with the proposed dose of Recarbrio.

The most common adverse reactions observed in patients treated with Recarbrio included nausea, diarrhea, headache, fever and increased liver enzymes. Recarbrio should not be used in patients taking ganciclovir unless the benefits outweigh the risks as seizures have been reported. 

Recarbrio is administered by a health care professional via intravenous infusion over 30 minutes, every 6 hours for 4 to 14 days. 

EGATEN (triclabendazole)
Manufacturer: Novartis Pharmaceuticals Corporation
Approval Date: February 13, 2019

FDA approved Egaten to treat fascioliasis, a parasitic infestation caused by two species of flatworms or trematodes that mainly the affect the liver, sometimes referred to as “liver flukes.”

Fascioliasis is an infectious disease caused by the parasitic flatworms Fasciola hepatica and Fasciola gigantica, also known as liver flukes. The initial infection is characterized by fever, abdominal pain, and increase elevation in liver enzymes. Over months to years, the disease may become chronic with occasional pain in the abdomen, jaundice, anemia, and blockage of bile ducts where adult flukes live. During this phase, parasite eggs are present in the stool.

The FDA approval of Egaten is supported by data from clinical trials, in which more than 90% of patients treated with Egaten were cured of their clinical symptoms or no longer had parasite eggs in their stool.

Egaten may cause heart rhythm problems (QT prolongation) especially in those who have underlying heart rhythm problems or who take drugs that alter heart rhythm. The most common side effects of Egaten are pain in the abdomen, sweating, nausea, decreased appetite, and headache.

Egaten is a tablet taken by mouth in two divided doses 12 hours apart with total dosage determined by the patient’s weight.

NEUROLOGY

XCOPRI (cenobamate)
Manufacturer: SK Life Science Inc
Approval Date: November 21, 2019

FDA approved Xcopri tablets to treat partial-onset seizures in adults.

The FDA approval of Xcopri is based primarily on evidence from two randomized, double-blind, placebo-controlled clinical trials comprising 655 patients with partial-onset seizures, conducted at 147 sites in the United States, Europe, Asia, Australia, Israel and South Africa. 

In these studies, patients had partial-onset seizures with or without secondary generalization for an average of approximately 24 years and median seizure frequency of 8.5 seizures per 28 days during an 8-week baseline period. 

During the trials, doses of 100, 200, and 400 mg daily of Xcopri reduced the percent of seizures per 28 days compared with the placebo
group. The recommended maintenance dose of Xcopri, following a titration (medication adjustment) period, is 200 mg daily; however,
some patients may need an additional titration to 400 mg daily,
the maximum recommended dose, based on their clinical response and tolerability.

Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS), also known as multiorgan hypersensitivity, has been reported among patients taking Xcopri. During the clinical trials, some patients
experienced DRESS, including one fatality when Xcopri was titrated rapidly. However, trial results do not support that the risk of DRESS
is prevented by slower titration. Xcopri should not be used in patients with hypersensitivity to cenobamate or any of the inactive ingredients in Xcopri.

The most common side effects that patients in the clinical trials reported were somnolence, dizziness, fatigue, diplopia, and headaches.

Xcopri is a tablet drug that is taken orally once daily beginning with an initial low dose that may be increased every 2 weeks according to a schedule decided by the health care provider. 

REYVOW (lasmiditan)
Manufacturer: Eli Lilly and Company
Approval Date: October 11, 2019

FDA approved Reyvow tablets for the acute treatment of migraine with or without aura in adults.

A higher percentage of patients who received Reyvow were pain free 2 hours after the treatment, in comparison to patients who received placebo. Also, a higher percentage of patients who received Reyvow were free of their most bothersome migraine associated symptoms (such as light sensitivity, sound sensitivity, or nausea) two hours after the treatment, in comparison to patients who received placebo.

The most common side effects of Reyvow include dizziness, fatigue, tingling in extremities, and sleepiness. Significant drowsiness can also occur, therefore patients should exercise caution and not operate a vehicle
within 8 hours of dosage. Other serious side effects include sedation,
the potential for medication overuse headache, and serotonin syndrome. Serotonin syndrome is a rare, serious, and potentially life threating
condition which may be more likely to occur if Reyvow is used with
antidepressants called selective serotonin reuptake inhibitors and serotonin and norepinephrine reuptake inhibitors.

Reyvow is taken orally as needed.

NOURIANZ (istradefylline)
Manufacturer: Kyowa Kirin, Inc
Approval Date: August 27, 2019

FDA approved Nourianz tablets as an add-on treatment to levodopa/carbidopa in adult patients with Parkinson disease (PD) experiencing off episodes. An off episode is a time when a patient’s medications are not working well, causing an increase in PD symptoms, such as tremor and difficulty walking.

The FDA approval of Nourianz is supported by clinical trials (Trial 1/ NCT00456586, Trial 2/NCT00199407, Trial 3/NCT00455507, Trial 4/NCT00955526) of 1,160 patients with PD whose symptoms were not well controlled while receiving their regular PD treatment. Trial 1 was conducted in the United States and Canada, Trial 2 in the United States, and Trials 3 and 4 in Japan.

Patients were selected to receive either Nourianz or a placebo pill once daily for 12 weeks.  In all trials, patients kept daily diaries of the number of hours they were awake and the number of hours of off time. The benefit was evaluated by measuring the change from baseline in total daily off time in patients receiving Nourianz and placebo.

In all four studies, patients treated with Nourianz experienced a statistically significant decrease from baseline in daily off time compared to patients receiving a placebo.  

The most common adverse effects included uncontrolled movement, hallucinations, and unusual urges, related to impulse control or compulsive behavior. Nourianz’s most common side effects also include dizziness, constipation, nausea, and insomnia. 

Nourianz is a tablet taken orally once daily in addition to drugs for the treatment of PD that contain levodopa/carbidopa combination.

WAKIX (pitolisant)
Manufacturer: Harmony Bioscience
Approval Date: August 14, 2019

FDA approved Wakix tablets to treat excessive daytime sleepiness in adults with narcolepsy. 

The FDA approval of Wakix was based on evidence from two trials, plus a third trial to determine side effects. Trials were conducted in Europe and South America where adult patients received Wakix or a placebo for 8 weeks. Neither patient nor health care provider knew who was receiving treatment. Results consisted of comparing changes in daytime sleepiness among placebo and treatment groups using the Epworth Sleepiness Scale (ESS). The ESS asks patients to rate the likelihood that they would fall asleep while doing eight daily activities (such as sitting and reading or watching television). Patients rate each item from 0 (would never doze) to 3 (high chance of dozing). 

Patients who received Wakix had less daytime sleepiness in comparison to patients who received placebo. 

In the placebo-controlled clinical trials conducted in patients with narcolepsy with or without cataplexy, the most common adverse reactions (≥5% and twice placebo) for Wakix were insomnia (6%), nausea (6%), and anxiety (5%). Other adverse reactions that occurred at ≥2% and more frequently than in patients treated with placebo included headache, upper respiratory infection, musculoskeletal pain, heart rate increased, hallucinations, irritability, abdominal pain, sleep disturbance, decreased appetite, cataplexy, dry mouth, and rash.

Wakix is a tablet taken orally once daily in the morning upon wakening.

MAYZENT (siponimod)
Manufacturer: Novartis Pharmaceuticals Corporation
Approval Date: March 26, 2019

FDA approved Mayzent tablets to treat adults with relapsing forms of multiple sclerosis (MS), to include clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease.

The FDA approval of Mayzent is based on results from a 1651 patient clinical trial that compared Mayzent to a placebo group for patients with secondary progressive multiple sclerosis who had evidence of disability progression in the prior 2 years and no relapses in the 3 months prior to enrollment. atients received Mayzent or placebo tablets once daily for up to 37 months. Neither the patients nor the health care providers knew which treatment was being given until the trial was completed. 

In the trial, Mayzent reduced the risk of disability progression. Twenty-six percent of patients who received Mayzent had confirmed progression of disability that was sustained over a 3-month period compared to 32% of patients who received placebo.

The most common adverse reactions reported by patients receiving Mayzent in the clinical trials include headache, high blood pressure and liver function test increases.

Mayzent is taken orally once daily and is initially started at a low dose. The dose is gradually increased over 5 to 6 days.

SUNOSI (solriamfetol)
Manufacturer: Jazz Pharmaceuticals, Inc
Approval Date: March 20, 2019

FDA approved Sunosi, a dual-acting dopamine and norepinephrine reuptake inhibitor, to improve wakefulness in adults with narcolepsy or obstructive sleep apnea (OSA).

The FDA approval of Sunosi is based on results from five different clinical trials with 622 patients with narcolepsy or OSA. All trials enrolled adults aged 18 to 75 years of age and had a placebo group for comparison. The benefit of Sunosi was assessed by determining the difference in Epworth Sleepiness Scale (ESS) and Maintenance of Wakefulness Test (MWT) before and during treatment. The ESS is an 8-item questionnaire where patients rate their perceived likelihood of falling asleep during usual daily life activities. The MWT measures the number of minutes an individual can remain awake during the daytime in a darkened, quiet environment.

Overall, patients treated with Sunosi remained awake longer and had decreased daytime sleepiness compared with patients treated with placebo.

The most common side effects of Sunosi are headache, nausea, decreased appetite, difficulty sleeping, and anxiety.

Sunosi is a tablet that is taken orally once daily. The dose may be adjusted, and the dose range depends on whether the drug is taken for narcolepsy or OSA. Patients who have OSA should continue modalities to treat airway obstruction while taking Sunosi.