FDA Approves First Respiratory Syncytial Virus (RSV) Vaccine - Arexvy from GSK

On 3 May 2023, the U.S. Food and Drug Administration approved Arexvy, the first respiratory syncytial virus (RSV) vaccine approved for use in the United States.

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

RSV is a highly contagious virus that causes infections of the lungs and breathing passages in individuals of all age groups.

RSV circulation is seasonal, typically starting during the fall and peaking in the winter.

In older adults, RSV is a common cause of lower respiratory tract disease (LRTD), which affects the lungs and can cause life-threatening pneumonia and bronchiolitis (swelling of the small airway passages in the lungs).

According to the U.S.Centers for Disease Control and Prevention, each year in the U.S., RSV leads to approximately 60,000-120,000 hospitalizations and 6,000-10,000 deaths among adults 65 years of age and older.

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 U.S. 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 have received Arexvy and the participants who have received a placebo, the vaccine significantly reduced the risk of developing RSV-associated LRTD by 82.6% and reduced the risk of developing severe RSV-associated LRTD 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 4 participants who received placebo.

The FDA is requiring the company to conduct a postmarketing study to assess the signals of serious risks for Guillain-Barré syndrome and ADEM.

In addition, although not an FDA requirement, the company has committed to assess atrial fibrillation in the postmarketing study

 

Bristol Myers Squibb Receives European Commission Approval for Breyanzi (lisocabtagene maraleucel) for Relapsed or Refractory Large B-cell Lymphoma After One Prior Therapy

Bristol Myers Squibb has received approval from the European Commission for Breyanzi (lisocabtagene maraleucel; liso-cel), a chimeric antigen receptor (CAR) T cell therapy directed towards CD19, for the treatment of adult patients suffering from diffuse large B-cell lymphoma (DLBCL), high grade B-cell lymphoma (HGBCL), primary mediastinal large B-cell lymphoma (PMBCL), and follicular lymphoma grade 3B (FL3B). The treatment is intended for patients who have relapsed within 12 months of completion of, or have shown refractory response to, first-line chemoimmunotherapy.

Approval of Breyanzi was granted after the positive results obtained from the Phase 3 TRANSFORM trial, where the therapy exhibited significant and clinically relevant advancements in the primary endpoint of event-free survival (EFS), and in key secondary endpoints such as complete responses (CR) and progression-free survival (PFS) when compared to standard treatment (which involves salvage immunochemotherapy followed by high-dose chemotherapy and hematopoietic stem cell transplant [HSCT]).  The treatment demonstrated a manageable and well-established safety profile.

In the TRANSFORM study, Breyanzi more than quadrupled median EFS compared to standard therapy (10.1 months vs. 2.3 months) at the time of prespecified interim analysis with a median follow-up of 6.2 months. Results of the primary analysis, with a median follow-up of 17.5 months were consistent with the interim analysis, with median EFS not reached for Breyanzi (95% CI: 9.5-NR) vs. 2.4 months for standard therapy (95% CI: 2.2-4.9).

With Breyanzi, the majority (73.9%) of patients achieved a CR compared to less than half (43.5%) of those who were treated with standard therapy. Median PFS was not reached (95% CI: 12.6-NR) with Breyanzi vs. 6.2 months (95% CI: 4.3-8.6) with standard therapy

The safety profile of Breyanzi is well-established, and in the TRANSFORM study, occurrences of cytokine release syndrome (CRS) and neurologic events were generally low-grade, and mostly resolved quickly with standard protocols and without the use of prophylactic steroids.

Boehringer Ingelheim's spesolimab receives US FDA approval for generalized pustular psoriasis flares in adults

Boehringer Ingelheim have announced that the U.S. Food and Drug Administration have approved spesolimab as a treatment option for generalized pustular psoriasis (GPP) flares in adults.

Spesolimab, marketed in the U.S. as SPEVIGO, is a novel, selective antibody that blocks the activation of the interleukin-36 receptor (IL-36R), a signaling pathway within the immune system shown to be involved in the pathogenesis of GPP.

The FDA’s approval of spesolimab is based on results from the pivotal EFFISAYIL 1 Phase II clinical trial. In the 12-week trial, patients experiencing a GPP flare were treated with spesolimab or placebo. Most patients at the outset of the trial had a high, or very high, density of pustules, and impaired quality of life. After one week, 54% of patients treated with spesolimab showed no visible pustules compared to placebo (6%).1

In addition to the U.S. approval, spesolimab is currently under review by several other regulatory authorities. To date, spesolimab has received Breakthrough Therapy Designation in the U.S., China and Taiwan, Priority Review in the U.S. and China, Orphan Drug Designation in the U.S., Korea, Switzerland and Australia, Rare Disease Designation and fast track in Taiwan, for the treatment of GPP flares. The European Medicines Agency validated the marketing authorization application for spesolimab in GPP in October 2021 and the submission is currently under evaluation.

Novartis drug Ilaris® approved by FDA to treat active systemic juvenile idiopathic arthritis, a serious form of childhood arthritis

Novartis announced today that the US Food and Drug Administration (FDA) has approved Ilaris(canakinumab) for the treatment of active systemic juvenile idiopathic arthritis (SJIA) in patients aged 2 years and older. Ilaris is the first interleukin-1 beta (IL-1 beta) inhibitor approved for SJIA and the only treatment approved specifically for SJIA that is given as a once-monthly subcutaneous injection. SJIA is a rare and disabling form of childhood arthritis characterized by spiking fever, rash and arthritis that can affect children as young as 2 years old and can continue into adulthood

This approval was based on two Phase III trials in SJIA patients, aged 2–19, showing significant improvement in the majority of Ilaris-treated patients. Study 1 showed that 84% of patients treated with one subcutaneous dose of Ilaris achieved the primary endpoint of the adapted pediatric American College of Rheumatology 30 (ACR30), compared to 10% achievement of ACR30 for placebo at Day 15. In the open-label part of Study 2, 92 of 128 patients attempted corticosteroid tapering. Of those 92 patients, 62% were able to substantially reduce their use of corticosteroids, and 46% completely discontinued corticosteroids. In the controlled portion of Study 2, there was a 64% relative reduction in the risk of flare for patients in the Ilaris group as compared to those in the placebo group 

Source: Novartis

New drug approved by US FDA for the treatment of COPD

The U.S. Food and Drug Administration today approved Breo Ellipta (fluticasone furoate and vilanterol inhalation powder) for the long-term, once-daily, maintenance treatment of airflow obstruction in patients with chronic obstructive pulmonary disease (COPD), including chronic bronchitis and/or emphysema. It is also approved to reduce exacerbations of COPD in patients with a history of exacerbations. 

COPD is a serious lung disease that worsens over time. Symptoms can include chest tightness, chronic cough and excessive phlegm. Cigarette smoking is the leading cause of COPD, according to the National Heart, Lung, and Blood Institute, and COPD is the third leading cause of death in the United States.

Breo Ellipta works by decreasing inflammation in the lungs and helping the muscles around the airways of the lungs stay relaxed to increase airflow and reduce exacerbations in patients with COPD.

“COPD is a serious disease that makes breathing difficult,” said Curtis Rosebraugh, M.D., M.P.H., director, Office of Drug Evaluation II, Center for Drug Evaluation and Research, FDA. “The availability of new long-term maintenance medications provides additional treatment options for the millions of Americans who suffer with COPD.”

Breo Ellipta is a combination of fluticasone furoate, an inhaled corticosteroid, and vilanterol, a long-acting beta2-adrenergic agonist (LABA). The safety and efficacy of Breo Ellipta were evaluated in 7,700 patients with a clinical diagnosis of COPD. Those treated showed improved lung function and reduced exacerbations compared to placebo.

The drug carries a boxed warning that LABAs increase the risk of asthma-related death. The safety and efficacy of Breo Ellipta in patients with asthma have not been established, and it is not approved for the treatment of asthma.

The FDA approved Breo Ellipta with a patient medication guide that includes instructions for use and information about the potential risks of taking the drug. Breo Ellipta should not be used as a rescue therapy to treat sudden breathing problems (acute bronchospasm) and is not recommended for people younger than 18 years.

Breo Ellipta may cause serious side effects, including increased risks of pneumonia and bone fractures. The most common side effects reported by patients using Breo Ellipta included inflammation of the nasal passage (nasopharyngitis), upper respiratory tract infection, headache, and oral candidiasis (thrush).

Breo Ellipta was developed by GlaxoSmithKline, Research Triangle Park, N.C., in collaboration with San Francisco-based Theravance.

Source: FDA

First generic Lexapro to treat depression and anxiety disorder

On March 14, 2012, the U.S. Food and Drug Administration approved the first generic Lexapro (escitalopram tablets) to treat both depression and generalized anxiety disorder in adults.

Depression is characterized by symptoms that interfere with a person's ability to work, sleep, study, eat, and enjoy once-pleasurable activities. Episodes of depression often recur throughout a person's lifetime.

Signs and symptoms of major depression include: depressed mood, loss of interest in usual activities, significant change in weight or appetite, insomnia or excessive sleeping (hypersomnia), restlessness/pacing (psychomotor agitation), increased fatigue, feelings of guilt or worthlessness, slowed thinking or impaired concentration, and suicide attempts or thoughts of suicide.

People with generalized anxiety disorder (GAD) are filled with exaggerated worry and tension, even though there is little or nothing to provoke it. They anticipate disaster and are overly concerned about health issues, money, family problems, or difficulties at work. GAD is diagnosed when a person worries excessively about a variety of everyday problems for at least six months. People with GAD can’t relax, startle easily, and have difficulty concentrating.

Source: FDA

FDA expands use of Prevnar 13 vaccine for people ages 50 and older

The U.S. Food and Drug Administration has approved the expanded use of Prevnar 13, a pneumococcal 13-valent conjugate vaccine for people ages 50 years and older to prevent pneumonia and invasive disease caused by the bacterium, Streptococcus pneumoniae.

Pneumococcal pneumonia, caused when the bacterium Streptococcus pneumoniae infects the lungs, is the most common disease caused by this bacterium in adults. When the bacterium invades parts of the body that are normally free from germs, such as the blood or spinal fluid, the disease is considered “invasive.”

“According to recent information for the United States, it is estimated that approximately 300,000 adults 50 years of age and older are hospitalized yearly because of pneumococcal pneumonia,” said Karen Midthun, M.D., director of FDA’s Center for Biologics Evaluation and Research.

The new use for Prevnar 13 was approved under the agency’s accelerated approval pathway, which allows for earlier approval of treatments for serious and life-threatening illnesses. The pathway allows for the demonstration of effectiveness of a vaccine using an immune marker that is reasonably likely to predict clinical benefit.

In randomized, multi-center studies in the United States and Europe, people 50 and older received either Prevnar 13 or Pneumovax 23, a licensed pneumococcal vaccine also approved for use in this age group. The studies showed that for the 12 common serotypes, Prevnar 13 induced antibody levels that were either comparable to or higher than the levels induced by Pneumovax 23.

The safety of Prevnar 13 was evaluated in about 6,000 people ages 50 and older who received Prevnar 13 and who had and had not previously received Pneumovax 23. Common adverse reactions reported with Prevnar 13 were pain, redness, and swelling at the injection site, limitation of movement of the injected arm, fatigue, headache, chills, decreased appetite, generalized muscle pain, and joint pain. Similar reactions were observed in those who received Pneumovax 23.

Accelerated approval is granted on the condition that a clinical trial is conducted during the post-approval marketing of the vaccine to verify the anticipated clinical benefit. An additional trial in 85,000 people ages 65 and older, with no previous history of receiving Pneumovax 23, is underway to confirm the clinical benefit of Prevnar 13 in the prevention of pneumococcal pneumonia.

Prevnar 13 is already approved for use in children ages 6 weeks through 5 years for the prevention of invasive disease caused by 13 different serotypes of the bacterium Streptococcus pneumoniae and for the prevention of otitis media caused by seven of the serotypes of the bacterium. 

The approval of Prevnar 13 for adults 50 years and older supports the Department of Health and Human Services’ Healthy People 2020 objectives

Prevnar 13 is manufactured by Collegeville, Pa.-based Wyeth Pharmaceuticals.

Source: FDA

FDA approves mechanical cardiac assist device for children with heart failure

The U.S. Food and Drug Administration today approved a medical device that supports the weakened heart of children with heart failure to help keep them alive until a donor for a heart transplant can be found.

The mechanical pulsatile cardiac assist device is called the EXCOR Pediatric System, made by a German company, Berlin Heart. The device comes in graduated sizes to fit children from newborns to teens.

“This is a step forward, it is the first FDA-approved pulsatile mechanical circulatory support device specifically designed for children,” said Susan Cummins, M.D., M.P.H, chief pediatric medical officer in the FDA’s Center for Devices and Radiological Health. “Previous adult heart assist devices were too large to be used in critically ill children to keep them alive while they wait to get a new heart.”

The device consists of one or two external pneumatic (driven by air) blood pumps, multiple tubes to connect the blood pumps to heart chambers and the great arteries, and the driving unit.

Heart failure in children is much less common than in adults. Heart transplantation offers effective relief from symptoms. However, far fewer pediatric sized donor hearts are available for transplantation than for adults, limiting the use of heart transplantation in children and prolonging the waiting period until transplant can occur. In infants, the median waiting time for a donor heart is 119 days. Overall a reported 12-17 percent of children and 23 percent of infants die while on the wait list for a heart transplant. 

In the primary U.S. study group of 48 patients, the use of the device was found to improve survival to transplant in patients when compared with the use of extracorporeal membrane oxygenation (ECMO) which is the current standard of care, although not FDA approved. Stroke, which can cause serious brain deficits, is a risk of the EXCOR Pediatric System. 

The EXCOR was designated as a Humanitarian Use Device (HUD) by the Office of Orphan Products Development at the FDA. This designation is for medical devices intended to benefit patients in the treatment or diagnosis of a disease or condition that affects fewer than 4,000 individuals in the United States annually. The device was approved under a Humanitarian Device Exemption (HDE), a type of marketing application that is similar to a premarket approval application in that the level of safety required for approval is the same. Rather than having to show a reasonable assurance of effectiveness, devices submitted under the HDE marketing route need to prove that the probable benefit from use of the device outweighs the probable risk of illness or injury from its use to obtain the FDA’s approval.

The FDA approval of an HDE authorizes an applicant to market the device subject to certain use restrictions. After the passing of the Pediatric Medical Device Safety and Improvement Act of 2007, HUDs intended and labeled for use in a pediatric population are permitted to be marketed for profit. 

The FDA’s Orphan Products Grant Program supported the U.S. clinical trials for the EXCOR Pediatric System with grants of $400,000 per year for three years.

For more information:

• Designating Humanitarian Use Devices

The FDA, an agency within the U.S. Department of Health and Human Services, protects the public health by assuring the safety, effectiveness, and security of human and veterinary drugs, vaccines and other biological products for human use, and medical devices. The agency also is responsible for the safety and security of our nation’s food supply, cosmetics, dietary supplements, products that give off electronic radiation, and for regulating tobacco products.

FDA permits marketing of the first hand-held device to aid in the detection of bleeding in the skull

The U.S. Food and Drug Administration today allowed marketing of the first hand-held device intended to aid in the detection of life-threatening bleeding in the skull called intracranial hematomas, using near-infrared spectroscopy.

The device, called the Infrascanner Model 1000, can help health care providers identify patients with critical head injuries who need an immediate brain imaging study.

Intracranial hematomas occur when blood from a ruptured blood vessel collects within the brain or between the skull and the brain. As blood expands within the brain or in the narrow space between the brain and the skull, the brain becomes compressed. This can produce symptoms such as headaches, vomiting, dizziness, lethargy, weakness in the arm or leg on one side of the body, seizures, or unconsciousness. An intracranial hematoma can be life-threatening if it is not treated immediately.

According to the Centers for Disease Control and Prevention, each year about 1.7 million people in the United States experience a traumatic brain injury.

 

The Infrascanner, Model 1000, uses a scanner that directs near-infrared light, a wavelength of light that can penetrate tissue and bone, into the skull. Blood from intracranial hematomas absorbs the light differently than other areas of the brain. The scanner detects differences in light absorption (optical density) and transmits the information wirelessly to a display on a hand-held computer.

By comparing the optical density from a series of scans of specific areas on both sides of the skull, a trained health care provider can use the information provided by the device, in conjunction with other clinical information, to determine the likelihood of an intracranial hematoma and the need for further diagnostic procedures, such as a computed tomography (CT) scan. 

“While patients with suspected brain injuries routinely receive a CT scan, this portable device offers emergency room physicians a non-invasive mechanism to aid in assessing whether an immediate CT scan is needed,” said Christy Foreman, director of the Office of Device Evaluation at FDA’s Center for Devices and Radiological Health.

The FDA reviewed data for the Infrascanner Model 1000 through the “de novo” classification process, a regulatory pathway for some low to moderate risk medical devices that are not comparable to a legally marketed device.

The FDA granted the de novo petition for the Infrascanner Model 1000 based on a review of data comparing results from 383 CT scans of adult subjects with Infrascanner scan results. The Infrascanner was able to detect nearly 75 percent of the hematomas detected by CT scan. When CT scans detected no hematoma, the Infrascanner detected no hematoma 82 percent of the time. The Infrascanner Model 1000, however, is not a substitute for a CT scan.

The FDA is specifying special controls in an accompanying regulation classifying the Infrascanner Model 

1000 as a Class II device with special controls. The special controls provide information about specific risks that must be addressed by other manufacturers who may wish to market a similar device.

The Infrascanner Model 1000 is manufactured by InfraScan Inc. of Philadelphia.

For more information:

• FDA: Medical Devices

The FDA, an agency within the U.S. Department of Health and Human Services, protects the public health by assuring the safety, effectiveness, and security of human and veterinary drugs, vaccines and other biological products for human use, and medical devices. The agency also is responsible for the safety and security of our nation’s food supply, cosmetics, dietary supplements, products that give off electronic radiation, and for regulating tobacco products.