Courtesy: US Food and Drug Administration

The US Food and Drug Administration (FDA) was busy throughout the first quarter of 2023. With more than a dozen novel drug approvals, multiple emergency use authorizations, a slew of advisory committee meetings, and more, FDA decisions have impacted almost every specialty in medicine during the first 90 days of the year.

In this recap article, we will be highlighting the top 10 approvals of the first quarter of the year. Further in the article, we shine a spotlight on other top regulatory decisions that have defined the first quarter of the year.

Interested in the most anticipated upcoming regulatory decisions?
Check out our coverage of the top decisions to watch in Q2 2023.

Top 10 FDA Approvals of Q1 2023

FDA Approves Narcan Nasal Spray for Over-the-Counter Use

As a result of the ongoing opioid epidemic, few therapies have gained the notoriety of naloxone hydrochloride nasal spray in recent years. Better known as Narcan, the opioid antagonist received its initial approval as a prescription drug from the FDA in 2015.

In a historic move, on March 29, 2023, the FDA approved 4 mg naloxone hydrochloride nasal spray for nonprescription, over-the-counter (OTC) use. To earn this new indication, Emergent BioSolutions was required to provide data demonstrating the drug’s safety and efficacy as directed in its proposed labeling and show consumers can understand how to use the drug without the supervision of a healthcare professional.

FDA Approves Albuterol/Budesonide as First-in-Class Asthma Rescue Treatment

On January 11, 2023, albuterol/budesonide (Airspura) became the first treatment approved by the FDA with an indication for as-needed treatment or prevention of bronchoconstriction and to reduce the risk of exacerbations in people with asthma aged 18 years and older.

Developed through a partnership between Aviation and first-in-class, pressurized metered-dose inhaler, fixed-dose combination rescue medication containing albuterol and budesonide, the approval of albuterol/budesonide is based on the results of a phase 3 clinical program including 4 trials.

FDA Approves Lecanemab for the Treatment for Alzheimer Disease

On January 6, 2023, the FDA approved the first novel drug of 2023, with a nod to lecanemab-irmb (Leqembi) for the treatment of Alzheimer’s disease. Approved through the FDA’s accelerated approval pathway based on the results of the phase 3 Clarity AD trial, the agent represents the second member of the class, behind only aducanumab, to receive such an indication.

According to the FDA, the accelerated approval of lecanemab is based on the observed reduction in amyloid beta plaque seen within the clinical program. Additionally, the FDA pointed out the prescribing information for the agent will include a warning for amyloid-related imaging abnormalities.

Related:Special Edition Mind Moments: Lecanemab Approved for Alzheimer Disease

Bexagliflozin Receives FDA Approval for Type 2 Diabetes in Adults

The second novel drug approval of 2023, bexagliflozin (Brenzavvy) received an indication from the FDA as an adjunct to diet and exercise for improving glycemic control in adults with type 2 diabetes on January 20, 2023. An SGLT2 inhibitor from TheracosBio, the approval is based on a clinical program consisting of 23 trials and comes less than 2 months after the agency approved bexagliflozin, under the brand name Bexacat, as the first oral treatment for cats with diabetes mellitus.

According to the FDA, bexagliflozin can be initiated in adults with type 2 diabetes with an eGFR greater than 30 mL/min/1.73m2 and is not indicated for the treatment of type 2 diabetes in patients with end stage renal disease or who are receiving dialysis.

FDA Approves Omaveloxolone as First Friedreich’s Ataxia Drug

Another novel drug approval, omaveloxolone (Skyclarys) became the first therapy agent to receive approval for the treatment of Friedreich’s ataxia on February 28, 2023, which is befittingly recognized as Rare Disease Day. A rare, inherited, degenerative disease that damages the nervous system, characterized by impaired coordination and walking, Friedrich’s ataxia impacts about 1 in every 50,000 people, according to the FDA.

The approval of omaveloxolone supported by efficacy and safety findings from the randomized, double-blind, placebo-controlled MOXIe Part 2 trial as well as a post hoc propensity-matched analysis of the open-label MOXIe Extension study. In their release, the FDA noted omaveloxolone had received orphan drug, fast track, priority review and rare pediatric disease designations during the approval process.

Daprodustat Receives FDA Approval for Anemia Caused by CKD on Dialysis

The FDA kicked off the month of February with the approval of daprodustat (Jesduvroq) for anemia caused by chronic kidney disease for adult patients who have been receiving dialysis for at least four months. Approved on February 1, 2023, daprodustat is the first oral agent to receive such an indication and was the fifth novel drug approval for the FDA in 2023.

Approved with support of the ASCEND program, daprodustat was the subject of an October 2022 CRDAC meeting where the committee voted 13-3 vote in favor of an indication for people with CKD on dialysis but 11-5 against an indication for the non-dialysis patient population. In their release, the FDA noted daprodustat has a boxed warning for an increased risk of thrombotic vascular events including death, heart attack, stroke, and blood clots in the lungs, legs, or dialysis access site.

FDA Approves First Drug for Rare Neurodevelopmental Disorder Rett Syndrome

On March 13, 2023, trofinetide (Daybue) became the first treatment to receive approval from the FDA for treatment of Rett syndrome. Indicated for the treatment of Rett syndrome, which is a rare disease characterized by developmental regression, including the loss of communication skills and purposeful hand use, and gait abnormalities, the agent stands poised to have a major impact on the quality of life for the approximately 4500 patients with Rett syndrome in the US.

Related: Trofinetide Approval Brings Encouragement for Rett Disease, Rare Neurodevelopmental Disorders

FDA Approves Pegcetacoplan Injection for Geographic Atrophy

On February 17, 2023, the FDA approved their first therapy for geographic atrophy with the approval of pegcetacoplan injection (Syfovre). A leading cause of blindness in the US, the approval of pegcetacoplan for geographic atrophy was awarded to Apellis Pharmaceuticals and is based on data from the phase 3 OAKS and DERBY trials.

In the multicenter, randomized, double-masked, sham-controlled studies, results indicated use of pegcetacoplan in monthly and every-other-month dosing intervals was associated with a reduced rate of geographic atrophy at 24 months. In our related coverage, hear from Charles Wykoff, MD, PhD, director of Clinical Research at Retina Consultants of Texas, as he reacts to the historic approval.

Related: Charles Wykoff, MD, Reacts to Approval of Pegcetacoplan for GA

Zavegepant Becomes First FDA-Approved CGRP-Targeting Nasal Spray for Acute Migraine

Neurologists had a new agent added to their armamentarium for treatment of acute migraine with the approval of zavegepant in early March. Announced on March 10, 2023, the approval marked the ninth novel drug of the year from the FDA and made the zavegepant the first and only calcitonin gene-related peptide receptor antagonist nasal spray indicated for the acute treatment of migraine in adults.

Approval is based on results of a pivotal phase 3 trial where use was associated with statistically significant improvements for pain freedom and freedom from most bothersome symptom at 2 hours post-dose relative to placebo therapy. The nasal spray is expected to be available in pharmacies in July 2023.

Tidepool Loop Mobile App Receives FDA Marketing Clearance

In late January 2023, the FDA granted marketing clearance to Tidepool Loop for use with compatible devices for automated insulin dosing to help manage type 1 diabetes in persons 6 years of age and older. A prescription-only mobile application, Tidepool Loop joins a suite of software tools that includes Tidepool Web, Tidepool Mobile, and Tidepool Uploader.

The result of a patient-led project, Tidepool Loop is compatible with integrated CGMs and alternate controller-enabled pumps to automatically increase, decrease, and suspend delivery of basal insulin based on iCGM readings and predicted glucose values. In addition to these features, the Tidepool Loop mobile application also possesses the ability to recommend and deliver correction boluses when glucose values are predicted to exceed predefined thresholds.

Related: Diabetes Dialogue: FDA Clearance of Tidepool Loop (Preview Below)

Other Top Regulatory News

Voluntary Recall Announced for Levothyroxine Sodium Oral Solution for Hypothyroidism

On February 2, 2023, the FDA issued a bulletin announcing IBSA Pharma is recalling 27 lots of levothyroxine sodium (TIROSINT-SOL) oral solution due to potential for subpotency. According to the bulletin, company analyses found some lots had slight decreases below 95.0% of its labeled amount of levothyroxine sodium (T4). The recall did not apply to levothyroxine sodium capsules.

In their bulletin, the FDA warned over- or under-treatment with TIROSINT-SOL, which is indicated for hypothyroidism and pituitary thyrotropin, may have negative effects on growth and development, cardiovascular function, bone metabolism, reproductive function, cognitive function, emotional state, gastrointestinal function, and glucose and lipid metabolism.

Artificial Tears Eye Drop Scare

On February 2, 2023, the FDA issued a warning to consumer and health care practitioners not to purchase and to immediately discontinue use of EzriCare Artificial Tears or Delsam Pharma’s Artificial Tears due to potential bacterial contamination. OTC products manufactured by Global Pharma Healthcare Private Limited, the CDC had identified 55 patients in 12 states with infections linked to use of the products as of January 31, 2023.

In addition to the warning, the FDA also recommend the recall of all unexpired lots of these products due to the company’s current good manufacturing practice violations, including lack of appropriate microbial testing, formulation issues, and lack of proper controls concerning tamper-evident packaging. Before the end of 2023, the FDA would go on to recommend a recall of Delsam Pharma’s Artificial Eye ointment.

FDA Extends PDUFA Date for B-VEC Gene Therapy

Few areas have seen the rapid growth and fervor in recent years as cell and gene therapy. Among these is beremagene geperpavec (B-VEC) from Krystal Biotech, which is under review for an indication for treatment of dystrophic epidermolysis bullosa (DEB). On January 5, 2023, the FDA announced it was extending the initial February 17, 2023, PDUFA date by 3 months to May 19, 2023.

Omecamtiv Mecarbil’s Journey in HFrEF Comes to an End

After months of speculation on whether the selective cardiac myosin activator would receive approval,the heart failure community received its answer with Cytokinetics announcing receipt of a CRL for the New Drug Application of omecamtiv mecarbil as a treatment indicated for heart failure with reduced ejection fraction. Announced on February 28, the CRL noted additional clinical trial results assessing omecamtiv mecarbil were required to establish evidence of efficacy for this patient population, according to Cytokinetics.

In their release, Cytokinetics pointed out they would forego any additional clinical trials for the investigative drug, and instead keep focus on the clinical development of cardiac myosin inhibitor aficamten for patients with hypertrophic cardiomyopathy.

Related: Heart Failure Community Argues for Omecamtiv Mecarbil Approval, Citing Unmet Need

Continued Advancement in the Treatment of COVID-19

Although it did not dominate headlines in the same fashion as it did in the first quarter of 2022, the COVID-19 pandemic remains a major issue in healthcare. During Q1 2023, the medical community continued to see advancements in the treatment of COVID-19.

On February 1, 2023, the FDA revised guidance for use of molnupiravir (Lagevrio) and nirmatrelvir/ritonavir (Paxlovid), which allows for use of either antiviral without a positive test for COVID-19. In an Antimicrobial Drugs Advisory Committee meeting held on March 16, 2023, 16 of the 17 committee members voted in favor of the benefit-risk profile as a treatment of mild-to-moderate COVID-19 in adults who are at high risk for progression to severe COVID-19, including hospitalization or death.