Top December 2022 FDA Approvals

In December, the US Food and Drug Administration (FDA) had a flurry of end-of-the-year approvals relevant to conditions often treated by nurse practitioners and PAs. Approvals include treatments for weight loss in adolescents, major depressive disorder, lung cancer detection, metastatic nonsmall cell lung cancer, multiple sclerosis, and lymphoma.

Wegovy® for Obesity in Adolescents

The FDA approved Wegovy^® (semaglutide injection) as an adjunct to a reduced calorie diet and increased physical activity for chronic weight management in pediatric patients aged 12 years and older with an initial body mass index (BMI) at the 95th percentile or greater for age and sex (obesity).

Wegovy contains semaglutide, a glucagon-like peptide-1 (GLP-1) receptor agonist. It works by targeting areas of the brain that regulate appetite and food intake. The approval was based on data from the STEP TEENS study, which included 201 participants 12 to less than 18 years. Patients were randomly assigned 2:1 to receive semaglutide administered once-weekly by subcutaneous injection or placebo for 68 weeks, in addition to lifestyle intervention.

At week 68, the mean change in BMI from baseline in the semaglutide group was -6.1%, while in the placebo group, it was 0.6% (estimated difference, -16.7 percentage points [95% CI, -20.3, -13.2]; P <.0001). Compared with placebo, a greater proportion of patients treated with semaglutide achieved a BMI reduction of 5% or more (77.1% vs 19.7%), 10% or more (65.1% vs 7.7%), and 15% or more (57.8% vs 4.0%). In addition to reductions in body weight, improvements in waist circumference, HbA_1c, and lipids (except for high-density lipoprotein cholesterol) were also observed with semaglutide compared with placebo.

Wegovy is supplied in prefilled, single-dose pens that deliver doses of 0.25 mg, 0.5 mg, 1 mg, 1.7 mg, or 2.4 mg.

Vraylar^® for Major Depressive Disorder

The FDA has approved Vraylar^® (cariprazine) as an adjunctive therapy to antidepressants in adults being treated for major depressive disorder (MDD).

Approval was based on data obtained from 2 trials in adults who met DSM-IV-TR or DSM-5 criteria for MDD and had an inadequate response to 1 to 3 courses of prior antidepressant therapy.

Results from a clinical trial demonstrated that adjunctive treatment with cariprazine 1.5 mg/day (n=250) was associated with an improved MADRS total score at week 6 compared with placebo (n=249) (placebo-subtracted difference, -2.5 [95% CI, -4.2, -0.9]; P =.005). The treatment effect in the cariprazine 3 mg/day arm (n=252) was not found to be statistically significant.

Findings from an 8-week, placebo-controlled study showed that adjunctive treatment with cariprazine 1 to 2 mg/day demonstrated improvement in the MADRS total score at week 8 vs placebo but did not meet statistical significance. Dosages of cariprazine between 2 mg and 4.5 mg per day were found to be statistically superior to placebo on the MADRS total score (placebo-subtracted difference, -2.2 [95% CI, -3.7, -0.6]).

The most common adverse reactions reported were akathisia, restlessness, fatigue, constipation, nausea, insomnia, increased appetite, dizziness, and extrapyramidal symptoms.

Idacio^®, a Citrate-Free Biosimilar to Humira

Idacio^® (adalimumab-aacf), a citrate-free biosimilar to Humira^® (adalimumab), has been approved by the FDA.

Idacio is a tumor necrosis factor and is approved for treating:

• Rheumatoid arthritis (RA): reducing signs/symptoms, inducing major clinical response, inhibiting the progression of structural damage, and improving physical function in adult patients with moderately to severely active RA; may be used alone or with methotrexate (MTX) or other nonbiologic DMARDs.
• Juvenile idiopathic arthritis (JIA): reducing signs/symptoms of moderately to severely active polyarticular JIA in patients 2 years of age and older; may be used alone or with MTX.
• Psoriatic arthritis (PsA): reducing signs/symptoms, inhibiting the progression of structural damage, and improving physical function in patients with active PsA; may be used alone or with nonbiologic DMARDs.
• Ankylosing spondylitis (AS): reducing signs/symptoms in adult patients with active AS.
• Crohn disease (CD): moderately to severely active CD in patients 6 years of age and older.
• Ulcerative colitis (UC): moderately to severely active UC in adult patients.
• Plaque psoriasis (PsO): treating adult patients with moderate to severe chronic PsO who are candidates for systemic therapy or phototherapy, and when other systemic therapies are medically less appropriate.

Idacio is supplied as 40 mg/0.8 mL in single-dose prefilled pens (Idacio Pen) and single-dose prefilled syringes. The product is expected to be available in July 2023.

Cytalux^® for Lung Cancer Detection During Surgery

The FDA has expanded the approval of Cytalux^® (pafolacianine) to include intraoperative identification of malignant and nonmalignant pulmonary lesions in adults diagnosed with or suspected of lung cancer.

Cytalux is a fluorescent drug that binds to folate receptor (FR)-expressing cancer cells and illuminates intraoperatively under infrared light. Approval was based on data collected from the open-label phase 3 ELUCIDATE study that evaluated the safety and efficacy of pafolacianine in 140 adults who underwent thoracoscopic or open segmental or subsegmental resection for primary lung lesions that were suspected or confirmed to be cancer.

The most common adverse reactions reported were infusion-related reactions, including nausea, vomiting, abdominal pain, flushing, dyspepsia, chest discomfort, blood pressure elevation, and hypersensitivity. Pafolacianine may also cause fetal harm; pregnancy testing prior to administration is recommended.

Cytalux is supplied as a single-dose vial containing 3.2 mg/1.6 mL (2 mg/mL) of pafolacianine.

Krazati^TM for KRAS^G12C-Mutated Locally Advanced or Metastatic NSCLC

The FDA granted accelerated approval to Krazati^TM (adagrasib) for the treatment of adults with KRAS^G12C-mutation locally advanced or metastatic non-small cell lung cancer (NSCLC) who have received at least 1 prior systemic therapy.

Approval was based on data from the open-label registration-enabling cohort of the phase 2 KRYSTAL-1 study that evaluated adagrasib in 112 adults with NSCLC harboring the KRAS^G12C mutation following prior systemic therapy. Participants were given 600 mg orally twice daily until disease progression or unacceptable toxicity.

After 9 months, results showed an objective response rate of 43% (95% CI, 34-53) and a disease control rate of 80% (95% CI, 71-87) in the intent-to-treat population. The median duration of response (DOR) was 8.5 months (95% CI, 6.2-13.8) with 58% of patients having a DOR lasting at least 6 months.

The most common adverse reactions reported were diarrhea, nausea, fatigue, vomiting, musculoskeletal pain, hepatotoxicity, renal impairment, dyspnea, edema, decreased appetite, cough, pneumonia, dizziness, constipation, abdominal pain, and QTc interval prolongation. Laboratory abnormalities included decreased lymphocytes, increased aspartate aminotransferase, decreased sodium, decreased hemoglobin, increased creatinine, decreased albumin, increased alanine aminotransferase, increased lipase, decreased platelets, decreased magnesium, and decreased potassium.

Krazati is supplied as 200 mg tablets in 120- and 180-count bottles and is expected to be available immediately.

Briumvi™ for Relapasing Multiple Sclerosis

Briumvi™ (ublituximab-xiiy) has been approved for the treatment of relapsing forms of multiple sclerosis, to include clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease, in adults.

Ublituximab-xiiy is a glycoengineered monoclonal antibody that targets CD20, a cell surface antigen present on pre-B and mature B lymphocytes. The approval was based on data from the phase 3 ULTIMATE I and ULTIMATE II trials, which evaluated the efficacy and safety of ublituximab-xiiy vs teriflunomide in patients with relapsing multiple sclerosis. Patients were randomly assigned to receive either ublituximab-xiiy 150 mg via intravenous infusion on day 1 and 450 mg on day 15, followed by a 450 mg dose every 6 months or teriflunomide 14 mg orally, once daily.

Results from both trials showed that treatment with ublituximab-xiiy demonstrated a statistically significant reduction in annualized relapse rate (ARR) over a 96-week period compared with teriflunomide (primary endpoint). In ULTIMATE I, treatment with ublituximab-xiiy resulted in an ARR of 0.076 vs 0.188 for teriflunomide, representing a relative reduction of 59% (P <.001). In ULTIMATE II, treatment with ublituximab-xiiy resulted in an ARR of 0.091 vs 0.178 for teriflunomide, representing a relative reduction of 49% (P =.002).

The most common adverse reactions reported with treatment included infusion reactions and upper respiratory tract infections.

Briumvi is supplied as a 150 mg/6 mL single-dose vial containing a preservative-free solution for intravenous use. The product is expected to be available in the first quarter of 2023.

Lunsumio^® for Relapsed/Refractory Follicular Lymphoma

The FDA granted accelerated approval to Lunsumio^® (mosunetuzumab-axgb) for the treatment of adults with relapsed or refractory (R/R) follicular lymphoma (FL) after 2 or more lines of systemic therapy.

Mosunetuzumab-axgb is a first-in-class CD20xCD3 T-cell engaging bispecific antibody that targets CD20 on the surface of B cells and CD3 on the surface of T cells. The approval was based on data from an open-label, multicenter, multi-cohort phase 2 study (GO29781), which evaluated the efficacy, safety and pharmacokinetics of mosunetuzumab-axgb in adults with R/R FL who had received at least 2 prior therapies, including an anti-CD20 monoclonal antibody and an alkylating agent.

Results showed mosunetuzumab-axgb induced high and durable response rates, with an objective response rate of 80% (n=72/90 [95%CI, 70-88]), of which 60% achieved complete response and 20% achieved partial response. The median duration of response (DOR) was 22.8 months (95% CI, 10-not reached), with a majority of patients maintaining response for at least 12 (62% [95% CI, 50-74]) and 18 months (57% [95% CI, 44-70]). The median time to first response was 1.4 months (range, 1.1 to 8.9).

The approval carries a Boxed Warning associated with a risk of cytokine release syndrome (CRS), including serious or life-threatening reactions. The most common adverse reactions (incidence at least 20%) were CRS, fatigue, rash, pyrexia, and headache. The most common Grade 3 or 4 laboratory abnormalities (incidence at least 10%) were decreased lymphocyte count, decreased phosphate, increased glucose, decreased neutrophil count, increased uric acid, decreased white blood cell count, decreased hemoglobin, and decreased platelets.

Lunsumio is supplied as a single-dose vial containing 1 mg/mL or 30 mg/30 mL preservative-free solution of mosunetuzumab-axgb. Treatment is administered only as an intravenous infusion.

This article originally appeared on Clinical Advisor