Estimated reading time: 12 minutes

In some of the most notable pharmaceutical approvals from 2023, drugs for RSV, CF, COVID-19, sickle cell disease, and opioid overdose received an FDA stamp in 2023.

(Click on each headline to jump to the article below.)



1) FDA Approves First RSV Vaccine. In clinical trials, GSK’s Arexvy significantly reduced the risk of developing RSV-associated lower respiratory tract disease by 82.6% and reduced the risk of developing severe RSV-associated lower respiratory tract disease by 94.1% in adults age 60 and older.  

2) FDA Approves Narcan Nasal Spray for OTC Use. The FDA approved Narcan 4 mg naloxone hydrochloride nasal spray for over-the-counter, nonprescription use. The approval is the first for a naloxone product without a prescription.

3) FDA Approves First CRISPR-based Therapy for Sickle Cell Disease. The FDA approved the first cell-based gene therapies for the treatment of sickle cell disease in patients 12 years and older. One therapy, Casgevy, is the first FDA-approved treatment to utilize the genome editing technology CRISPR/Cas9.

4) FDA Grants Kalydeco Expanded Approval for Infants with Cystic Fibrosis. The medication now is approved for use in children with cystic fibrosis ages 1 month to less than 4 months old who have at least one mutation in their cystic fibrosis transmembrane conductance regulator gene. .

5) FDA Approves Paxlovid for High-Risk COVID-19 Patients. Pfizer’s Paxlovid is the fourth drug—and first oral antiviral pill—approved by the FDA to treat COVID-19 in adults.


1) FDA Approves First RSV Vaccine


The US Food and Drug Administration has approved Arexvy, the first respiratory syncytial virus (RSV) vaccine approved for use in the United States. 

Arexvy (GlaxoSmithKline) is approved for the prevention of lower respiratory tract disease caused by RSV in individuals 60 years of age and older.

“Older adults, in particular those with underlying health conditions, such as heart or lung disease or weakened immune systems, are at high risk for severe disease caused by RSV,” says Peter Marks, MD, PhD, director of the FDA’s Center for Biologics Evaluation and Research. “Today’s approval of the first RSV vaccine is an important public health achievement to prevent a disease which can be life-threatening and reflects the FDA’s continued commitment to facilitating the development of safe and effective vaccines for use in the United States.”

The safety and effectiveness of Arexvy is based on the FDA’s analysis of data from an ongoing, randomized, placebo-controlled clinical study conducted in the US and internationally in individuals 60 years of age and older. The main clinical study of Arexvy was designed to assess the safety and effectiveness of a single dose administered to individuals 60 years of age and older. Participants will remain in the study through three RSV seasons to assess the duration of effectiveness and the safety and effectiveness of repeat vaccination. Data for a single dose of Arexvy from the first RSV season of the study were available for the FDA’s analysis. 

In this study, approximately 12,500 participants have received Arexvy, and 12,500 participants have received a placebo. Among the participants who received Arexvy and the participants who received a placebo, the vaccine significantly reduced the risk of developing RSV-associated lower respiratory tract disease by 82.6% and reduced the risk of developing severe RSV-associated lower respiratory tract disease by 94.1%.

Among a subset of these clinical trial participants, the most commonly reported side effects by individuals who received Arexvy were injection site pain, fatigue, muscle pain, headache, and joint stiffness/pain. Among all clinical trial participants, atrial fibrillation within 30 days of vaccination was reported in 10 participants who received Arexvy and four participants who received placebo.

2) FDA Approves Narcan Nasal Spray for OTC Use


The FDA approved Narcan 4 mg naloxone hydrochloride nasal spray for over-the-counter (OTC), nonprescription use. The approval for Narcan (Emergent BioSolutions) is the first for a naloxone product without a prescription.

Naloxone is a medication that rapidly reverses the effects of opioid overdose and is the standard treatment for opioid overdose. Today’s action paves the way for the life-saving medication to reverse an opioid overdose to be sold directly to consumers in places like drug stores, convenience stores, grocery stores and gas stations, as well as online. 

The timeline for availability and price of this OTC product is determined by the manufacturer. The FDA will work with all stakeholders to help facilitate the continued availability of naloxone nasal spray products during the time needed to implement the Narcan switch from prescription to OTC status, which may take months. Other formulations and dosages of naloxone will remain available by prescription only. 

Drug overdose persists as a major public health issue in the United States, with more than 101,750 reported fatal overdoses occurring in the 12-month period ending in October 2022, primarily driven by synthetic opioids like illicit fentanyl. 

“The FDA remains committed to addressing the evolving complexities of the overdose crisis. As part of this work, the agency has used its regulatory authority to facilitate greater access to naloxone by encouraging the development of and approving an over-the-counter naloxone product to address the dire public health need,” said FDA Commissioner Robert M. Califf, M.D. “Today’s approval of OTC naloxone nasal spray will help improve access to naloxone, increase the number of locations where it’s available and help reduce opioid overdose deaths throughout the country. We encourage the manufacturer to make accessibility to the product a priority by making it available as soon as possible and at an affordable price.”   

Narcan nasal spray was first approved by the FDA in 2015 as a prescription drug. In accordance with a process to change the status of a drug from prescription to nonprescription, the manufacturer provided data demonstrating that the drug is safe and effective for use as directed in its proposed labeling. The manufacturer also showed that consumers can understand how to use the drug safely and effectively without the supervision of a healthcare professional. The application to approve Narcan nasal spray for OTC use was granted priority review status and was the subject of an advisory committee meeting in February 2023, where committee members voted unanimously to recommend it be approved for marketing without a prescription. 

The approval of OTC Narcan nasal spray will require a change in the labeling for the currently approved 4 mg generic naloxone nasal spray products that rely on Narcan as their reference listed drug product. Manufacturers of these products will be required to submit a supplement to their applications to effectively switch their products to OTC status. The approval may also affect the status of other brand-name naloxone nasal spray products of 4 mg or less, but determinations will be made on a case-by-case basis and the FDA may contact other firms as needed. 

The use of Narcan nasal spray in individuals who are opioid dependent may result in severe opioid withdrawal characterized by body aches, diarrhea, increased heart rate (tachycardia), fever, runny nose, sneezing, goose bumps, sweating, yawning, nausea or vomiting, nervousness, restlessness or irritability, shivering or trembling, abdominal cramps, weakness and increased blood pressure.

3) FDA Approves First CRISPR-based Therapy for Sickle Cell Disease

The FDA approved the first cell-based gene therapies for the treatment of sickle cell disease (SCD) in patients 12 years and older. One of these therapies, named Casgevy, is the first FDA-approved treatment to utilize CRISPR/Cas9, a novel genome editing technology. The approval signals an innovative advancement in the field of gene therapy, the FDA said in a news release.

Sickle cell disease is a group of inherited blood disorders affecting approximately 100,000 people in the US. It is most common in African Americans and, while less prevalent, also affects Hispanic Americans. The primary problem in sickle cell disease is a mutation in hemoglobin, a protein found in red blood cells that delivers oxygen to the body’s tissues. This mutation causes red blood cells to develop a crescent or “sickle” shape. These sickled red blood cells restrict the flow in blood vessels and limit oxygen delivery to the body’s tissues, leading to severe pain and organ damage called vaso-occlusive events (VOEs) or vaso-occlusive crises (VOCs). The recurrence of these events or crises can lead to life-threatening disabilities and/or early death. 

“Sickle cell disease is a rare, debilitating and life-threatening blood disorder with significant unmet need, and we are excited to advance the field especially for individuals whose lives have been severely disrupted by the disease by approving two cell-based gene therapies today,” said Nicole Verdun, MD, director of the Office of Therapeutic Products within the FDA’s Center for Biologics Evaluation and Research. “Gene therapy holds the promise of delivering more targeted and effective treatments, especially for individuals with rare diseases where the current treatment options are limited.” 

Casgevy

Casgevy (Vertex Pharmaceuticals Inc) is approved for the treatment of sickle cell disease in patients 12 years of age and older with recurrent vaso-occlusive crises. Casgevy is the first FDA-approved therapy utilizing CRISPR/Cas9, a type of genome editing technology. Patients’ hematopoietic (blood) stem cells are modified by genome editing using CRISPR/Cas9 technology. 

CRISPR/Cas9 can be directed to cut DNA in targeted areas, enabling the ability to accurately edit (remove, add, or replace) DNA where it was cut. The modified blood stem cells are transplanted back into the patient where they engraft (attach and multiply) within the bone marrow and increase the production of fetal hemoglobin (HbF), a type of hemoglobin that facilitates oxygen delivery. In patients with sickle cell disease, increased levels of HbF prevent the sickling of red blood cells.

Lyfgenia

The FDA also approved a cell-based gene therapy called Lyfgenia (Bluebird Bio Inc). Lyfgenia uses a lentiviral vector (gene delivery vehicle) for genetic modification and is approved for the treatment of patients 12 years of age and older with sickle cell disease and a history of vaso-occlusive events. With Lyfgenia, the patient’s blood stem cells are genetically modified to produce HbAT87Q, a gene-therapy derived hemoglobin that functions similarly to hemoglobin A, which is the normal adult hemoglobin produced in persons not affected by sickle cell disease. Red blood cells containing HbAT87Q have a lower risk of sickling and occluding blood flow. These modified stem cells are then delivered to the patient. 

Both products are made from the patients’ own blood stem cells, which are modified, and are given back as a one-time, single-dose infusion as part of a hematopoietic (blood) stem cell transplant. Prior to treatment, a patients’ own stem cells are collected, and then the patient must undergo myeloablative conditioning (high-dose chemotherapy), a process that removes cells from the bone marrow so they can be replaced with the modified cells in Casgevy and Lyfgenia. Patients who received Casgevy or Lyfgenia will be followed in a long-term study to evaluate each product’s safety and effectiveness. 

“These approvals represent an important medical advance with the use of innovative cell-based gene therapies to target potentially devastating diseases and improve public health,” said Peter Marks, MD, PhD, director of the FDA’s Center for Biologics Evaluation and Research. “Today’s actions follow rigorous evaluations of the scientific and clinical data needed to support approval, reflecting the FDA’s commitment to facilitating development of safe and effective treatments for conditions with severe impacts on human health.”

4) FDA Grants Kalydeco Expanded Approval for Infants with Cystic Fibrosis


BD (Becton, Dickinson and Company) has received FDA emergency use authorization for its new molecular diagnostic combination test for SARS-CoV-2, influenza A + B, and respiratory syncytial virus (RSV).

The Respiratory Viral Panel for BD Max System is an RT- PCR assay that detects and differentiates the nucleic acid of SARS-CoV-2, flu A, flu B and RSV in as little as two hours for the first result, with the simplified and automated workflow of the BD Max System.

The test is available for use on the BD Max Molecular Diagnostic System. It uses a single nasal swab or a single nasopharyngeal swab sample to identify and distinguish if a patient has COVID-19, the flu, RSV or some combination of the three, with results available in as little as two hours.

According to BD, the test helps eliminate the need for multiple tests or doctor visits and can help clinicians implement the right treatment plan quickly. The co-testing approach also helps to increase testing capacity during the busy flu/RSV season and speed time to diagnosis.

“While fears of a ‘tripledemic’ this respiratory season have largely diminished, accurately differentiating influenza and RSV from COVID-19 and providing appropriate treatment remains a challenge for our customers,” said Nikos Pavlidis, vice president of Molecular Diagnostics at BD. “This diagnostic test provides the ability to identify multiple pathogens using a single sample and can quickly pinpoint the causative virus or viruses and enable clinicians to administer appropriate treatment early in the course of infection.”

The BD Max System is already in use at thousands of hospitals and laboratories worldwide, and each unit is capable of analyzing hundreds of samples over a 24-hour period. 

5) FDA Approves Paxlovid for High-Risk COVID-19 Patients

The US FDA has granted full approval to Pfizer’s oral antiviral Paxlovid for the treatment of mild-to-moderate COVID-19 in adults who are at high risk for progression to severe COVID-19, including hospitalization or death. 

Paxlovid (nirmatrelvir tablets and ritonavir tablets, co-packaged for oral use) is the fourth drug—and first oral antiviral pill—approved by the FDA to treat COVID-19 in adults, according to a release from the FDA.

Paxlovid manufactured and packaged under the emergency use authorization and distributed by the US Department of Health and Human Services will continue to be available to ensure continued access for adults, as well as treatment of eligible children ages 12 to 18 who are not covered by this approval. Paxlovid is not approved or authorized for use as a pre-exposure or post-exposure prophylaxis for the prevention of COVID-19.

“While the pandemic has been challenging for all of us, we have made great progress mitigating the impact of COVID-19 on our lives,” says Patrizia Cavazzoni, MD, director for the FDA’s Center for Drug Evaluation and Research, in a release. “Today’s approval demonstrates that Paxlovid has met the agency’s rigorous standards for safety and effectiveness and that it remains an important treatment option for people at high risk for progression to severe COVID-19, including those with prior immunity. The FDA remains committed to working with sponsors to facilitate the development of new prevention and treatment options for COVID-19.”

The efficacy of Paxlovid was primarily supported by the final results of the EPIC-HR clinical trial. EPIC-HR was a randomized, double-blind, placebo-controlled clinical trial studying Paxlovid for the treatment of non-hospitalized symptomatic adults with a laboratory-confirmed diagnosis of SARS-CoV-2 infection. 

Patients were adults 18 years of age and older with a prespecified risk factor for progression to severe disease or were 60 years and older regardless of prespecified chronic medical conditions. All patients had not received a COVID-19 vaccine and had not been previously infected with COVID-19.

Paxlovid significantly reduced the proportion of people with COVID-19 related hospitalization or death from any cause through 28 days of follow-up by 86% compared to placebo among patients treated within five days of symptom onset and who did not receive COVID-19 therapeutic monoclonal antibody treatment. In this analysis, 977 patients received Paxlovid, and 989 patients received placebo, and among these patients, 0.9% who received Paxlovid were hospitalized due to COVID-19 or died from any cause during 28 days of follow-up compared to 6.5% of the patients who received the placebo.