The US Food and Drug Administration (FDA) approved several drugs in May and June 2022 relevant to conditions often treated my nurse practitioners and PAs. Approvals include treatments for Crohn disease, plaque psoriasis, Wilson disease, eosinophilic esophagitis, H pylori, severe alopecia areata.
Dupixent® for Eosinophilic Esophagitis
The FDA has approved Dupixent® (dupilumab) for the treatment of eosinophilic esophagitis in patients 12 years of age and older, weighing at least 88 lbs.
Approval was based on data gathered from a randomized, double-blind, placebo controlled trail that tested the efficacy and safety of Dupixent. The trial had 2 arms (Parts A and B) that last 24 weeks. Patients in both parts of the trial were randomly assigned to receive 300 mg of Dupixent subcutaneously once weekly or placebo.
Patients taking Dupixent achieved significant rates of remission as compared with those on placebo. In Part A, 59.5% (n = 25/42) of patients in the Dupixent arm achieved significant remission at week 24 vs 5.1% (n = 2/39) in the placebo arm (treatment difference, 57%; 95% CI, 40.9-73.1). Patients in the Dupixent arm experienced a 21.92 point improvement in disease symptoms, as measured by the Dysphagia Questionnaire (DSQ) score, vs a 9.60 point improvement for placebo.
In Part B, 58.8% (n = 47/80) of patients in the Dupixent arm achieved significant remission vs 6.3% (n = 5/79) in the placebo arm (treatment difference, 53.5%; 95% CI, 41.2-65.8). Patients in the Dupixent arm experienced a 23.8 point improvement in disease symptoms, as measured by the DSQ score, vs a 13.90 point improvement for placebo.
The most common adverse reactions included reactions at the injection site, upper respiratory tract infections, joint pain, and herpes viral infections. Dupixent is also approved for the treatment of atopic dermatitis, asthma, and chronic rhinosinusitis with nasal polyps.
VoqueznaTM Triple PakTM and VoqueznaTM Dual PakTM for H. Pylori
VoqueznaTM Triple PakTM (vonoprazan, amoxicillin, clarithromycin) and VoqueznaTM Dual PakTM (vonoprazan, amoxicillin) has been approved by the FDA for the treatment of Helicobacter pylori infection in adults.
Approval was based on data obtained from a randomized, controlled, double-blind triple therapy/open-label dual therapy, study that tested the safety and efficacy of Voqeuzna in 1046 adults diagnosed with H pylori.
Patients were randomly assigned 1:1:1 to receive Voquezna Triple Pak (vonoprazan 20 mg twice daily, amoxicillin 1000 mg twice daily, clarithromycin 500 mg twice daily), Voquezna Dual Pak (vonoprazan 20 mg twice daily, amoxicillin 1000 mg 3 times daily) for 14 days.
Results showed that in the modified intent-to-treat (mITT) population, H pylori eradication rates were 84.7% and 78.5% with Voquezna Triple and Dual Pak, respectively, in patients who did not have a clarithromycin or amoxicillin resistant strain of H pylori at baseline compared with 78.8% with lansoprazole triple therapy (P <.0001 and P <.01 for non-inferiority [primary endpoint]).
Additionally, Voquezna Triple and Dual Pak were shown to be superior to lansoprazole triple therapy in patients who had a clarithromycin resistant strain of H pylori at baseline and in the overall population with the following H pylori eradication rates, respectively:
- Clarithromycin resistant strain at baseline: 65.8% and 69.6% vs 31.9% (both P <.0001);
- Overall population: 80.8% and 77.2% vs 68.5% (P =.0003 and P =.01, respectively).
For Voquezna Triple Pak, the most common adverse reactions were dysgeusia, diarrhea, vulvovaginal candidiasis, headache, abdominal pain, and hypertension. For Voquezna Dual Pak, the most common adverse reactions reported were diarrhea, abdominal pain, vulvovaginal candidiasis and nasopharyngitis.
Vtama® for Plaque Psoriasis
The FDA has approved Vtama® (tapinarof cream) for the treatment of plaque psoriasis in adults 18 years of age and older.
The approval was based on data obtained from 2 identical phase 3 trials that assessed the safety and efficacy of Vtama in 1025 adults (18 to 75 years of age) diagnosed with plaque psoriasis.
The primary end point for both studies was hope that patients would earn a Physician Global Assessment (PGA) score of clear (0) or almost clear (1). Results from both trials showed that 36% and 40% of patients met the primary end point, respectively. Following 12 weeks of treatment, 73 Vtama patients achieved complete disease clearance (PGA 0).
The most common adverse reactions reported were folliculitis, nasopharyngitis, contact dermatitis, headache, pruritus, and influenza. Vtama is supplied in a 60 g tube, each gram of cream contains 10 mg of tapinarof.
CuvriorTM for Wilson Disease
CuvriorTM (trientine tetrahydrochloride) was approved by the FDA for treatment of adults with stable Wilson disease who are tolerant to penicillamine and have normal levels of copper in their system. Cuvrior contains trientine, a copper chelator that eliminates absorbed copper from the body by forming a stable complex that is then eliminated through urine. Trientine also chelates copper in the intestinal tract, reducing copper absorption.
The approval was based on data collected from the randomized, open-label, phase 3 CHELATE study that compared the safety and efficacy of Cuvrior with penicillamine in 53 adult patients with Wilson disease. All patients have been receiving penicillamine for at least 1 year.
At the start of the study, patients entered a 12-week baseline period and continued to receive their established total daily dosage of penicillamine for 12 weeks. At week 12, patients were randomly assigned to either remain on penicillamine (n=27) or to switch to Cuvrior (n=26) for the 24-week post randomization period. The primary endpoint was the mean serum non-ceruloplasmin copper (NCC) level at 24 weeks post randomization (week 36).
Results showed that at week 36, patients treated with Cuvrior had a similar mean NCC level to those treated with penicillamine, 56 mcg/L vs 46 mcg/L, respectively (difference, -9; 95% CI, -24, 6). Mean 24-hour urinary copper excretion was observed to be lower in patients receiving Cuvrior compared with penicillamine (274 mcg/24 hrs vs 511 mcg/24 hrs [difference, 236 mcg/24 hrs; 95% CI, 111-361]).
The most common adverse reactions reported were abdominal pain, change of bowel habits, rash, alopecia, and mood swings.
Cuvrior is supplied as a tablet containing 300 mg of trientine tetrahydrochloride and is expected to be available in early 2023.
Skyrizi® for Crohn Disease
The FDA has approvedSkyrizi® (risankizumab-rzaa), an interleukin-23 inhibitor, for the treatment of moderate to severe active Crohn disease in adults.
The approval was based on a pair of phase 3 induction studies (ADVANCE and MOTIVATE) and a phase 3 maintenance study (FORTIFY) that evaluated the safety and efficacy of Skyrizi in adults diagnosed with Crohn disease.
In the ADVANCE and MOTIVATE studies, patients were randomly assigned to receive Skyrizi 600 mg, 1200 mg, or placebo as intravenous (IV) induction therapy. In the FORTIFY study, patients who responded to IV induction therapy were then randomly assigned to receive Skyrizi 360 mg or placebo.
Results from ADVANCE and MOTIVATE showed a greater proportion of patients treated with Skyrizi 600 mg met the following efficacy endpoints vs placebo at week 12, respectively (all P <.001):
- Clinical remission (primary endpoint; as measured by Crohn Disease Activity Index [CDAI]): 45% and 42% vs 25% and 20%;
- Endoscopic response (primary endpoint; defined as a decrease in Simple Endoscopic score for CD [SES-CD] of >50% from the baseline or a decrease of at least 2 points for patients with a baseline score of 4 and isolated ileal disease, based on central reading): 40% and 29% vs 12% and 11%;
- Clinical response (defined as a reduction of CDAI ≥100 points from baseline): 60% and 60% vs 37% and 30%;
- Endoscopic remission (defined as SES-CD ≤4 and at least a 2-point reduction from baseline, with no individual subscore greater than 1, based on central reading): 24% and 19% vs 9% and 4%.
Findings showed that the onset of clinical response and clinical remission occurred as early as week 4 in a greater proportion of patients in the Skyrizi arm. The Skyrizi 1200 mg dosage did not demonstrate additional treatment benefit over the 600 mg dosage and is not a recommended regimen.
In the FORTIFY study, results showed that 57% and 48% of patients treated with Skyrizi 360 mg achieved clinical remission and endoscopic response, respectively, at week 52 vs 46% and 22% of those who received placebo (both P <.05). Moreover, 41% of patients treated with Skyrizi 360 mg achieved endoscopic remission compared with 13% of those who received placebo; this endpoint was not statistically significant.
The most common adverse reactions reported during induction treatment included upper respiratory infections, headache and arthralgia. During maintenance treatment, common adverse reactions reported were arthralgia, injection site reactions, abdominal pain, anemia, pyrexia, back pain, arthropathy, and urinary tract infections.
Syrizi is supplied in a 600 mg/10 mL single-dose vial for IV infusion to be administered by a health care provider in the induction period and a 360 mg/2.4 mL single-dose prefilled cartridge for subcutaneous injection maintenance treatment (can be self-injected).
Imcivree® for Weight Management in Bardet-Biedl Syndrome
Imcivree® (setmelanotide subcutaneous injection) was approved by the FDA for chronic weight management in patients 6 years of age and older with monogenic or syndromic obesity due to Bardet-Biedl syndrome.
Bardet-Biedl syndrome is a rare genetic disorder that affects multiple organ systems and includes symptoms like obesity, hyperphagia, retinal degeneration, and reduced kidney function.
Imcivree is a melanocortin 4 receptor (MC4R) agonist that works to reduce hunger and promote weigh loss by decreasing calorie intake and increasing energy expenditure. The approval was based on data from a phase 3 study that evaluated the safety and efficacy in patients 6 years and older diagnosed with Bardet-Biedl syndrome and obesity (BMI ≥30 for adults or weight ≥ 97th percentile for pediatric patients using growth chart assessments). Patients were randomly assigned to received Imcivree or placebo for 14 weeks, followed by an open-label treatment period, were all patients received Imcivree for 38 weeks.
Results indicated significant reductions in weight and hunger at 52 weeks. In patients aged ≥ 6 years with obesity due to BBS (N=31), treatment with Imcivree was associated with a mean BMI reduction of 7.9% without requirements for diet and exercise. After 52 weeks, 61.3% of Imcivree-treated patients achieved at least a 5% loss in BMI and 38.7% achieved at least a 10% loss in BMI. Additionally, hunger scores (assessed by the Daily Hunger Questionnaire Item 2) decreased in Imcivree-treated patients during the 14-week placebo-controlled period and during the open-label treatment period.
The most common adverse reactions included injection site reactions, skin hyperpigmentation, nausea, headache, diarrhea, abdominal pain, vomiting, depression, and spontaneous penile erection.
Olumiant® for Severe Alopecia Areata
Olumiant® (baricitinib)was approved by the FDA for treatment of severe alopecia areata in adults.
The approval was based on data from the randomized, double-blind, placebo-controlled phase 3 BRAVE-AA1 and BRAVE-AA2 trials that evaluated the safety and efficacy of Olumiant in 1200 adults with severe alopecia areata. Patients were randomly assigned to receive wither Olumiant 2 mg daily, Olumiant 4 mg daily, or placebo.
In the BRAVE-AA1 trial, 22% and 35% of patients treated with Olumiant 2 mg and 4 mg, respectively, achieved adequate scalp hair coverage as compared with 5% of those treated with placebo. In the BRAVE-AA2 trial, 17% and 32% of patients treated with Olumiant 2 mg and 4 mg, respectively, achieved adequate scalp hair coverage as compared with 3% of those treated with placebo.
The most common adverse reactions reported were upper respiratory tract infections, headache, acne, hyperlipidemia, increased creatinine phosphokinase, urinary tract infection, liver enzyme elevations, folliculitis, fatigue, lower respiratory tract infections, nausea, Candida infections, anemia, neutropenia, abdominal pain, herpes zoster, and increase in weight.
Olumiant is also used for the treatment of rheumatoid arthritis and COVID-19.
Radicava ORS® for Amyotrophic Lateral Sclerosis
The FDA has approved Radicava ORS® (edaravone oral suspension) for adults with amyotrophic lateral sclerosis (ALS).
Radicava ORS contains the same active ingredient as Radicava, which was originally approved in 2012 as an IV infusion for ALS treatment.
The approval was based on data collected from a 24-week, open-label phase 3 study that evaluated safety of Radicava ORS in 185 patients diagnosed with ALS. The bioavailability study showed comparable levels of edaravone in the bloodstream with the oral suspension under fasted conditions as that of the IV formulation.
Radicava ORS can be administered by mouth or via a feeding tube using a 5 mL oral syringe.
Adverse reactions were reported by at least 5% of patients and include muscular weakness, fall, fatigue, back pain, constipation, headache, and dyspnea.
1. Dupixent. Prescribing information. Sanofi and Regeneron; 2022. Accessed June 28, 2022. https://www.regeneron.com/downloads/dupixent_fpi.pdf
2. VoqueznaTriple Pak and Voquezna Dual Pak. Prescribing information. Phathom Pharmaceuticals, Inc.; 2022. Accessed June 29, 2022. http://www.phathompharma.com/wp-content/uploads/VOQUEZNA-TRIPLE-PAK-and-VOQUEZNA-DUAL-PAK-FDA-Final-Label-3.pdf
3. Vtama. Prescribing information. Dermavant Sciences; 2022. Accessed June 28, 2022. https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/215272s000lbl.pdf
4. Cuvrior. Prescribing information. Orphalan; 2022. Accessed June 28, 2022. https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/215760s000lbl.pdf
5. Skyrizi. Prescribing information. AbbVie; 2022. Accessed June 29, 2022. https://www.rxabbvie.com/pdf/skyrizi_pi.pdf
6. Imcivree. Prescribing information. Rhythm Pharmaceuticals; 2022. Accessed June 28, 2022. https://rhythm-vault-digital-publishing-production.s3.amazonaws.com/IMCIVREEPrescribingInformation.pdf
7. Olumiant. Prescribing information. Eli Lilly and Company; 2022. Accessed June 28, 2022. https://pi.lilly.com/us/olumiant-uspi.pdf
8. Radicava ORS. Prescribing information. Mitsubishi Tanabe Pharma America, Inc.; 2022. Accessed June 28, 2022. https://www.radicava.com/pdfs/radicava-prescribing-information.pdf