FDA Approves Magnetic Device System for Guiding Sentinel Lymph Node Biopsies in Certain Patients with Breast Cancer

 

Sentinel lymph nodes are the first lymph nodes to which cancer cells are most likely to spread from a primary tumor. For patients with breast cancer, testing the sentinel lymph nodes indicates whether the cancer has spread from the breast. A sentinel lymph node biopsy is used to identify, remove and examine lymph nodes to determine whether cancer cells are present.

 

The FDA has approved a magnetic device system for guiding lymph node biopsies in patients with breast cancer undergoing mastectomy. The Magtrace and Sentimag Magnetic Localization System (Sentimag System) uses magnetic detection during sentinel lymph node biopsy procedures to identify specific lymph nodes, known as sentinel lymph nodes, for surgical removal. Currently, a sentinel lymph node biopsy is performed after injection of radioactive materials and/or blue dye. This currently approved system offers patients undergoing mastectomy an option for their sentinel lymph biopsy procedure that does not require the injection of radioactive materials. A negative sentinel lymph node biopsy result suggests that cancer has not spread to nearby lymph nodes. A positive result may indicate that cancer is present in the sentinel lymph node and may be present in other nearby lymph nodes and, possibly, other organs. This information can help a doctor determine the stage of the cancer and develop an appropriate treatment plan.

 

The Sentimag System uses magnetic materials to guide the sentinel lymph node biopsy procedure. The system is comprised of a sensitive magnetic sensing probe and base unit designed to detect small amounts of Magtrace, the magnetic tracer drug that is injected into breast tissue. The Magtrace particles travel to lymph nodes and become physically trapped in them, facilitating magnetic detection of the lymph nodes. Following the injection of Magtrace, the Sentimag probe is applied to the patients’ skin in areas closest to the tumor site containing the lymph nodes. The sensing of the magnetic particles is indicated by changes in audio and visual alerts from the base unit, enabling the surgeon to move the hand-held probe around the area of the lymph nodes, and locate the sentinel lymph node or nodes (if there are more than one). The surgeon then makes a small incision and removes the node, which is checked by a pathologist for the presence of cancer cells.

 

The FDA evaluated data from a trial of 147 patients with breast cancer to compare the Sentimag System to the control method of injecting patients with blue dye and radioactive materials together and using a gamma probe to identify the sentinel lymph node. Patients were administered both methods to compare lymph node detection rates. The lymph node detection rate for the Sentimag System was 94.3% while the control method detection rate was 93.5%. Overall, 98.0% of patients had the same detection rate with both the Sentimag System and the control method. The most common reported adverse events, included breast discoloration, which is reported to disappear after three months in patients who underwent mastectomy, cardiac disorder (bradycardia) and potential allergic reaction to the magnetic materials. The Sentimag System is contraindicated in any patient with hypersensitivity to iron oxide or dextran compounds It is also not recommended for patients with iron overload disease or with a metal implant in the axilla or in the chest.

 

Magtrace may travel to regions away from the injection site such as liver or spleen, if injected directly into the bloodstream. In such cases the presence of Magtrace may cause image artifacts during Magnetic Resonance Imaging (MRI). Magtrace residues have not been reported to produce artifacts affecting imaging in X-ray, positron emission tomography (PET) scans, computed tomography (CT) scans, PET/CT scans or ultrasound studies.

 

The FDA reviewed the Sentimag System application using a coordinated, cross-agency approach. The clinical review was conducted by the FDA’s CDRH in consultation with the Center for Drug Evaluation and Research and with support from the FDA’s Oncology Center of Excellence, while all other aspects of review and the final product approval determination was conducted by the FDA’s CDRH.

 

The FDA granted approval of the Sentimag System to Endomagnetics Inc.

 

FDA Approves First Targeted Treatment for Patients with Relapsed or Refractory Acute Myeloid Leukemia Who Have a Certain Genetic Mutation

 

Acute myeloid leukemia (AML) is a rapidly progressing cancer that forms in the bone marrow and results in an increased number of abnormal white blood cells in the bloodstream and bone marrow. The National Cancer Institute at the National Institutes of Health estimates that approximately 19,520 people will be diagnosed with AML this year and approximately 10,670 of these patients will die of the disease in 2018.

 

The FDA approved Tibsovo (ivosidenib) tablets for the treatment of adult patients with relapsed or refractory AML who have a specific genetic mutation. This is the first drug in its class (IDH1 inhibitors) and is approved for use with an FDA-approved companion diagnostic used to detect specific mutations in the IDH1 gene in patients with AML. Tibsovo is an isocitrate dehydrogenase-1 inhibitor that works by decreasing abnormal production of the oncometabolite 2-hydroxyglutarate (2-HG), leading to differentiation of malignant cells. If the IDH1 mutation is detected in blood or bone marrow samples using an FDA-approved test, the patient may be eligible for treatment with Tibsovo. The FDA also approved the RealTime IDH1 Assay, a companion diagnostic that can be used to detect this mutation.

 

The efficacy of Tibsovo was studied in a single-arm trial of 174 adult patients with relapsed or refractory AML with an IDH1 mutation. The trial measured the percentage of patients with no evidence of disease and full recovery of blood counts after treatment (complete remission or CR), as well as patients with no evidence of disease and partial recovery of blood counts after treatment (complete remission with partial hematologic recovery or CRh). With a median follow-up of 8.3 months, 32.8% of patients experienced a CR orCRh that lasted a median 8.2 months. Of the 110 patients who required transfusions of blood or platelets due to AML at the start of the study, 37% went at least 56 days without requiring a transfusion after treatment with Tibsovo. Common side effects of Tibsovo include fatigue, increase in white blood cells, joint pain, diarrhea, shortness of breath, swelling in the arms or legs, nausea, pain or sores in the mouth or throat, irregular heartbeat (QT prolongation), rash, fever, cough and constipation. Women who are breastfeeding should not take Tibsovo because it may cause harm to a newborn baby.

 

Tibsovo must be dispensed with a patient Medication Guide that describes important information about the drug’s uses and risks. The prescribing information for Tibsovo includes a boxed warning that an adverse reaction known as differentiation syndrome can occur and can be fatal if not treated. Signs and symptoms of differentiation syndrome may include fever, difficulty breathing (dyspnea), acute respiratory distress, inflammation in the lungs (radiographic pulmonary infiltrates), fluid around the lungs or heart (pleural or pericardial effusions), rapid weight gain, swelling (peripheral edema) or liver (hepatic), kidney (renal) or multi-organ dysfunction. At first suspicion of symptoms, doctors should treat patients with corticosteroids and monitor patients closely until symptoms go away. Other serious warnings include a QT prolongation, which can be life-threatening. Electrical activity of the heart should be tested with an electrocardiogram during treatment. Guillain-Barre syndrome, a rare neurological disorder in which the body’s immune system mistakenly attacks part of its peripheral nervous system, has happened in people treated with Tibsovo, so patients should be monitored for nervous system problems.

 

The FDA granted this application Fast Track and Priority Review designations. Tibsovo also received Orphan Drug designation, which provides incentives to assist and encourage the development of drugs for rare diseases.

 

The FDA granted the approval of Tibsovo to Agios Pharmaceuticals, Inc. The FDA granted the approval of the RealTime IDH1 Assay to Abbott Laboratories.

 

First Drug Approved to Treat Smallpox

 

Prior to its eradication in 1980, variola virus, the virus that causes smallpox, was mainly spread by direct contact between people. Symptoms typically began 10 to 14 days after infection and included fever, exhaustion, headache and backache. A rash initially consisting of small, pink bumps progressed to pus-filled sores before finally crusting over and scarring. Complications of smallpox could include encephalitis (inflammation of the brain), corneal ulcerations (an open sore on the clear, front surface of the eye) and blindness. Though the World Health Organization declared smallpox, a contagious and sometimes fatal infectious disease, eradicated in 1980, there have been longstanding concerns that smallpox could be used as a bioweapon.

 

The FDA has approved TPOXX (tecovirimat), the first drug with an indication for treatment of smallpox. TPOXX was developed in conjunction with the U.S. Department of Health and Human Services’ Biomedical Advanced Research and Development Authority (BARDA).

 

TPOXX’s effectiveness against smallpox was established by studies conducted in animals infected with viruses that are closely related to the virus that causes smallpox, and was based on measuring survival at the end of the studies. More animals treated with TPOXX lived compared to the animals treated with placebo. TPOXX was approved under the FDA’s Animal Rule, which allows efficacy findings from adequate and well-controlled animal studies to support an FDA approval when it is not feasible or ethical to conduct efficacy trials in humans.

 

The safety of TPOXX was evaluated in 359 healthy human volunteers without a smallpox infection. The most frequently reported side effects were headache, nausea and abdominal pain. The FDA granted this application Fast Track and Priority Review designations. TPOXX also received Orphan Drug designation, which provides incentives to assist and encourage the development of drugs for rare diseases and a Material Threat Medical Countermeasure Priority Review Voucher, which provides additional incentives for certain medical products intended to treat or prevent harm from specific chemical, biological, radiological and nuclear threats.

 

The FDA granted approval of TPOXX to SIGA Technologies Inc.

 

Device Approved to Treat Breathing Difficulty in Severe Emphysema

 

The Centers for Disease Control and Prevention estimates that 3.5 million American adults have been diagnosed with emphysema. Emphysema, including severe emphysema, is a type of chronic obstructive pulmonary disease (COPD) due to damage to the air sacs (alveoli) in the lungs. Lung damage from emphysema is irreversible. The damaged alveoli can cause used air to become trapped in the lungs during exhalation. This can cause the diseased parts of the lung to get larger and put pressure on the healthy part of the lung, which makes it difficult to breathe. As a result, the body may not get the oxygen it needs. Treatment options are limited for people with emphysema who have severe symptoms that have not improved from taking medicines. These options include lung surgery, such as lung volume reduction or lung transplants, which may not be suitable or appropriate for all patients.

 

The FDA has approved a new device, the Zephyr Endobronchial Valve (Zephyr Valve), intended to treat breathing difficulty associated with severe emphysema. Using a flexible bronchoscope, the Zephyr Valves, similar in size to pencil erasers, are placed into the diseased areas of the lung airways during a hospital-based procedure. The design of the device is intended to prevent air from entering the damaged parts of the lung and allow trapped air and fluids to escape. During inhalation, the valves close, preventing air from entering the damaged part of the lung and during exhalation, the valves open, letting out trapped air, which is intended to relieve pressure. The FDA reviewed data from a multi-center study of 190 patients with severe emphysema. In this study, 128 patients were treated with Zephyr Valves and medical management according to current clinical guidelines, including medications (bronchodilators, corticosteroids, antibiotics or anti-inflammatory maintenance medications) and pulmonary rehabilitation, while 62 patients (the control group) received medical management only. Results of treatment were measured by how many patients in each arm of the study had at least a 15% improvement in pulmonary function scores (the volume of air that can forcibly be blown out in one second after full inhalation). At one year, 47.7% of patients treated with Zephyr Valves experienced at least a 15% improvement in their pulmonary function scores, compared with 16.8% of patients in the control group. Adverse events observed in the study include death, air leak (pneumothorax), pneumonia, worsening of emphysema, coughing up blood, shortness of breath and chest pain.

 

The Zephyr Valve device is contraindicated for patients with active lung infections; those who are allergic to nitinol, nickel, titanium or silicone; active smokers and those who are not able to tolerate the bronchoscopic procedure. Patients who have had major lung procedures, heart disease, large bubbles of air trapped in the lung or who have not responded to other treatments should talk with their providers to determine if the Zephyr Valve device is appropriate for them.

 

The Zephyr Valve was granted Breakthrough Device designation, meaning the FDA provided intensive interaction and guidance to the company on efficient device development, to expedite evidence generation and the agency’s review of the device. To qualify for such designation, a device must provide for more effective treatment or diagnosis of a life-threatening or irreversibly debilitating disease or condition, and meet one of the following criteria: the device must represent a breakthrough technology; there must be no approved or cleared alternatives; the device must offer significant advantages over existing approved or cleared alternatives; or the availability of the device is in the best interest of patients.

 

The FDA reviewed the Zephyr Valve device through the premarket approval review pathway, a regulatory pathway for the highest risk class of devices.

 

The FDA granted approval of the Zephyr Valve device to Pulmonx Inc.

 

FDA Approves First Drug Comprised of an Active Ingredient Derived from Marijuana to Treat Rare, Severe Forms of Epilepsy

 

Dravet syndrome is a rare genetic condition that appears during the first year of life with frequent fever-related seizures (febrile seizures). Later, other types of seizures typically arise, including myoclonic seizures (involuntary muscle spasms). Additionally, status epilepticus, a potentially life-threatening state of continuous seizure activity requiring emergency medical care, may occur. Children with Dravet syndrome typically experience poor development of language and motor skills, hyperactivity and difficulty relating to others.

 

Lennox-Gastaut syndrome begins in childhood. It is characterized by multiple types of seizures. People with Lennox-Gastaut syndrome begin having frequent seizures in early childhood, usually between ages 3 and 5. More than three-quarters of affected individuals have tonic seizures, which cause the muscles to contract uncontrollably. Almost all children with Lennox-Gastaut syndrome develop learning problems and intellectual disability. Many also have delayed development of motor skills such as sitting and crawling. Most people with Lennox-Gastaut syndrome require help with usual activities of daily living.

 

The FDA has approved Epidiolex (cannabidiol) [CBD] oral solution for the treatment of seizures associated with Lennox-Gastaut syndrome and Dravet syndrome, in patients two years of age and older. This is the first FDA-approved drug that contains a purified drug substance derived from marijuana. It is also the first FDA approval of a drug for the treatment of patients with Dravet syndrome.

 

CBD is a chemical component of the Cannabis sativa plant, more commonly known as marijuana. However, CBD does not cause intoxication or euphoria (the “high“) that comes from tetrahydrocannabinol (THC). It is THC (and not CBD) that is the primary psychoactive component of marijuana.

 

According to FDA, this approval serves as a reminder that advancing sound development programs that properly evaluate active ingredients contained in marijuana can lead to important medical therapies, and that the FDA is committed to this kind of careful scientific R&D development. FDA added that because of the adequate and well-controlled clinical studies that supported this approval, prescribers can have confidence in the drug’s uniform strength and consistent delivery that support appropriate dosing needed for treating patients with these complex and serious epilepsy syndromes.

 

Epidiolex’s effectiveness was studied in three randomized, double-blind, placebo-controlled clinical trials involving 516 patients with either Lennox-Gastaut syndrome or Dravet syndrome. Results showed that Epidiolex, taken along with other medications, was shown to be effective in reducing the frequency of seizures when compared with placebo. The most common side effects that occurred in Epidiolex-treated patients in the clinical trials were: sleepiness, sedation and lethargy; elevated liver enzymes; decreased appetite; diarrhea; rash; fatigue, malaise and weakness; insomnia, sleep disorder and poor quality sleep; and infections.

 

Epidiolex must be dispensed with a patient Medication Guide that describes important information about the drug’s uses and risks. As is true for all drugs that treat epilepsy, the most serious risks include thoughts about suicide, attempts to commit suicide, feelings of agitation, new or worsening depression, aggression and panic attacks. Epidiolex also caused liver injury, generally mild, but raising the possibility of rare, but more severe injury. More severe liver injury can cause nausea, vomiting, abdominal pain, fatigue, anorexia, jaundice and/or dark urine.

 

Under the Controlled Substances Act (CSA), CBD is currently a Schedule I substance because it is a chemical component of the cannabis plant. In support of this application, the company conducted nonclinical and clinical studies to assess the abuse potential of CBD. The FDA prepares and transmits, through the U.S. Department of Health and Human Services, a medical and scientific analysis of substances subject to scheduling, like CBD, and provides recommendations to the Drug Enforcement Administration (DEA) regarding controls under the CSA. DEA is required to make a scheduling determination.

 

The FDA granted Priority Review designation for this application. Fast-Track designation was granted for Dravet syndrome. Orphan Drug designation was granted for both the Dravet syndrome and Lennox-Gastaut syndrome indications.

 

The FDA granted approval of Epidiolex to GW Research Ltd.

FDA Approves Automated Insulin Delivery and Monitoring System for Use in Younger Pediatric Patients

 

The human pancreas naturally supplies a low, continuous rate of insulin, known as basal or background insulin. In patients with diabetes, the body’s ability to produce or respond to insulin is impaired. Because the pancreas does not make insulin in people with type 1 diabetes, patients must consistently monitor their glucose levels throughout the day and inject insulin with a syringe, pen or pump to avoid becoming hyperglycemic (high glucose levels). In addition, management of type 1 diabetes includes following a healthy eating plan and physical activity. Type 1 diabetes, also known as juvenile diabetes, is typically diagnosed in children and young adults.

 

The FDA has expanded the approval of the MiniMed 670G hybrid closed looped system, a diabetes management device that is intended to automatically monitor glucose (sugar) and provide appropriate basal insulin doses with little or no input from the user, to include individuals aged 7 to 13 with type 1 diabetes. The FDA originally approved this device in September 2017 for use in patients 14 years of age and older with type 1 diabetes.

 

The MiniMed 670G hybrid closed looped system works by measuring glucose levels in the body every five minutes and automatically adjusting insulin delivery by either administering or withholding insulin. The system includes: a sensor that attaches to the body to measure glucose levels under the skin; an insulin pump strapped to the body; and an infusion patch connected to the pump with a catheter that delivers insulin. While the device automatically adjusts insulin levels, users need to manually request insulin doses to counter carbohydrate consumption at mealtime.

 

The FDA evaluated data from a clinical trial of the MiniMed 670G hybrid closed looped system that included 105 individuals aged 7 to 11 years old. Study participants wore the device for approximately 3.5 months and participated in three phases of the study to evaluate both at-home use as well as remote use. The study found no serious adverse events associated with use of the MiniMed 670G and that the device is safe for use in people age 7 to 13 years with type 1 diabetes. Risks associated with use of the system may include hypoglycemia, hyperglycemia, as well as skin irritation or redness around the device’s infusion patch. As part of this approval, the FDA is requiring the product developer to conduct a post-market study to evaluate device performance in real-world settings in children between the ages of 7 and 13. This device is not approved for use in children 6 years of age or younger and in individuals who require less than eight units of insulin per day.

 

The expanded approval of MiniMed 670G hybrid closed looped system was granted to Medtronic.

 

Innovation at FDA

 

The following was taken from a posting on June 6, 2018 by FDA Voice, authored by Scott Gottlieb, M.D., and Anna Abram

 

Scientific advances in biotechnology, such as genome editing and synthetic biology, hold enormous potential to improve human and animal health, animal welfare, and food security. And researchers and companies based in the United States helped pioneer these technologies. To advance this progress, it’s key that the FDA adopt a regulatory approach to these technologies that’s as innovative and nimble as the opportunities that FDA is being tasked with evaluating. FDA is committed to helping ensure the safety of biotechnology products, while also facilitating innovation by applying a risk-based regulatory approach that provides developers with regulatory clarity and predictability and maintains public confidence in the regulatory system.

 

FDA is taking some new steps to approve products enabled by new techniques of biotechnology that have the potential to significantly enhance public health. For instance, new methods can be used to alter animals to minimize or prevent their ability to spread human disease. Genome editing in animals and plants also can be used to produce human drugs, devices, or biologics, including tissues or organs for xenotransplantation. Scientists are also exploring editing the genomes of animals with the goal of improving the health and welfare of food producing animals and public health, for example by reducing their susceptibility to diseases like novel influenzas and resistance to zoonotic or foreign animal diseases. Similar and equally beneficial applications of genome editing are currently being explored in food crops. These include the ability to develop disease-resistant plants and plants with increased resistance to environmental stress. Such advances can have many advantages to consumers, including better yields, more product variety, and healthier nutrient profiles.

 

FDA believes that it is uniquely committed and positioned – with the expertise, experience, credibility and trusted scientific framework – to advance innovation and support the development of products with immense potential for public benefit, since the breadth of FDA’s statutory authorities and regulatory framework allows it to comprehensively review the potential impacts of products on both human and animal health. For example, for genetically engineered animals, FDA evaluates not only the safety of food or drug products derived from that animal, but also the effect of the genetic alteration on the health of the animal. FDA has decades of experience successfully evaluating products of complex technologies, such as recombinant DNA-derived plant foods, medicines made with nanotechnology, and cellular and gene therapy products.

 

Moreover, because of the wide spectrum of products that FDA regulates, and the in-depth scientific and policy engagement that the agency has with innovators and counterpart regulatory agencies around the world, FDA can help facilitate the progression of research and development. For example, FDA is focused on the timely transition of technologies from animal research models to products intended for use in humans. As knowledge of genome editing applications increases over different product areas, FDA expect to build on those even greater synergies and increase its understanding to help with assessments of risks to human and animal health.

 

FDA will continue to apply a risk-based framework grounded in sound science to evaluate products of plant and animal biotechnology, and our framework will continue to evolve as science advances and experience with these technologies grows. FDA is looking forward to working with stakeholders to help understand current scientific information and describe challenges and gaps in regulatory science that are important for regulatory decision-making. FDA is also going to take new steps to help developers understand their responsibility to ensure product safety and we’ll identify ways to help reduce unnecessary regulatory burden and undue barriers to bring potential beneficial products to commercialization while ensuring their safety.

 

Protecting and promoting public health is FDA’s mission at the same time FDA wants to support innovation and sustaining public confidence. To help advance these goals, in early May, FDA formed a new Biotech Working Group. This Working Group is comprised of representatives from multiple FDA centers and offices. In the coming months, FDA will release an Action Plan that lays out the steps it intends to take to ensure that FDA will have a flexible regulatory framework for evaluating the safety of products that also supports plant and animal biotechnology innovation.

 

Our actions will focus on three key areas:

 

First, advancing and protecting public and animal health by promoting innovation through an efficient and predictable science- and risk-based regulatory framework; second, strengthening public outreach and communication through strong, effective and transparent engagement with stakeholders; and third, increasing engagement with domestic and international partners through coordinated and collaborative actions to support regulatory alignment and efficiency.

 

FDA is taking concrete and proactive steps to help ensure the safety of plant and animal biotechnology products, while promoting innovation and enhancing public and market confidence in FDA’s regulation of these products at home and abroad. FDA recognizes the tremendous opportunities offered by this new technology and is committed to developing a framework that allows these innovations to safely advance and fulfill the potential envisioned by those who are pioneering these approaches, as well as inspire public confidence in these methods. Clearly, the advance of these technologies holds significant public health promise and unlocking their full potential and competitiveness depends on the trust FDA builds now and in the years to come.

 

FDA Approves First Artificial Iris

 

Patients with iris defects may experience severe vision problems, as well as dissatisfaction with the appearance of their eye. Congenital aniridia is a rare genetic disorder in which the iris is completely or partially absent. This disorder affects approximately 1 in 50,000 to 100,000 people in the U.S. The iris controls the amount of light entering the eye, and those with aniridia have sensitivity to light and other severe vision problems.

 

The FDA has approved the CustomFlex Artificial Iris, the first stand-alone prosthetic iris in the United States. The CustomFlex Artificial Iris is a surgically implanted device to treat adults and children with aniridia or other damage to the eye. According to the FDA, this first artificial iris provides a novel method to treat iris defects that reduces sensitivity to bright light and glare, and also improves the cosmetic appearance of the eye. In addition to congenital aniridia, the CustomFlex Artificial Iris is indicated to treat iris defects due to other reasons or conditions, such as albinism, traumatic injury or surgical removal due to melanoma

 

The CustomFlex Artificial Iris is made of thin, foldable medical-grade silicone and is custom-sized and colored for each individual patient. A surgeon makes a small incision, inserts the device under the incision, unfolds it and smooths out the edges using surgical instruments. The prosthetic iris is held in place by the anatomical structures of the eye or, if needed, by sutures.

 

The safety and effectiveness of the CustomFlex Artificial Iris was demonstrated primarily in a non-randomized clinical trial of 389 adult and pediatric patients with aniridia or other iris defects. The study measured patients’ self-reported decrease in severe sensitivity to light and glare post-procedure, health-related quality of life, and satisfaction with the cosmetic improvement or appearance of the prosthesis. More than 70% of patients reported significant decreases in light sensitivity and glare as well as an improvement in health-related quality of life following the procedure. In addition, 94% of patients were satisfied with the artificial iris’ appearance.

 

The study found low rates of adverse events associated with the device or the surgical procedure. In the study, complications associated with the use of the CustomFlex Artificial Iris device included: device movement or dislocation, strands of device fiber in the eye, increased intraocular pressure, inflammation of the iris (iritis), adhesion of the iris to the cornea or lens (synechiae) and the need for secondary surgery to reposition, remove or replace the device. Complications associated with the surgical procedure included: increased intraocular pressure, blood leakage in the eye, swelling of the center of the retina (cystoid macular edema), secondary surgery, corneal swelling, iritis, and retinal detachment.

 

The CustomFlex Artificial Iris is contraindicated, or should not be used, in eyes with any of the following conditions: uncontrolled or severe chronic inflammation (uveitis), abnormally small eye size (microphthalmus), untreated retinal detachment, untreated chronic glaucoma, cataract caused by rubella virus, abnormal blood vessels on the iris (rubeosis), certain kinds of damaged blood vessels in the retina, and intraocular infections. It is also contraindicated for patients who are pregnant.

 

The CustomFlex Artificial Iris was approved through a premarket approval application (PMA), which is the most stringent type of device marketing application and generally required for high-risk devices. A PMA approval is primarily based on a determination by the FDA that the PMA contains sufficient valid scientific evidence that provides reasonable assurance that the device is safe and effective for its intended uses. CustomFlex Artificial Iris was granted Breakthrough Device designation, meaning the FDA provided intensive interaction and guidance to the company on efficient device development, to expedite evidence generation and the agency’s review of the device. To qualify for such designation, a device must provide for more effective treatment or diagnosis of a life-threatening or irreversibly debilitating disease or condition, and meet one of the following criteria: the device must represent a breakthrough technology; there must be no approved or cleared alternatives; the device must offer significant advantages over existing approved or cleared alternatives; or the availability of the device is in the best interest of patients.

 

The FDA granted approval of the CustomFlex Artificial Iris to Clinical Research Consultants, Inc.

 

FDA Approves a New Treatment for PKU

 

Phenylketonuria (PKU) is rare and serious genetic disease that affects about 1 in 10,000 to 15,000 people in the United States. Patients with PKU are born with an inability to break down phenylalanine (Phe), an amino acid present in protein-containing foods and high-intensity sweeteners used in a variety of foods and beverages. If untreated, PKU can cause chronic intellectual, neurodevelopmental and psychiatric disabilities. Lifelong restriction of phenylalanine intake through the diet is needed to prevent buildup of Phe in the body, which can cause long-term damage to the central nervous system.

 

The FDA has approved Palynziq (pegvaliase-pqpz) for adults with PKU. Palynziq is a novel enzyme therapy for adult PKU patients who have uncontrolled blood Phe concentrations on current treatment. The safety and efficacy of Palynziq were studied in two clinical trials in adult patients with PKU with blood phenylalanine concentrations greater than 600 ?mol/L on existing management. Most PKU patients in the Palynziq trials were on an unrestricted diet prior to and during the trials. The first trial was a randomized, open-label trial in patients treated with increasing doses of Palynziq administered as a subcutaneous injection up to a target dose of either 20 mg once daily or 40 mg once daily. The second trial was an 8-week, placebo-controlled, randomized withdrawal trial in patients who were previously treated with Palynziq. Patients treated with Palynziq achieved statistically significant reductions in blood phenylalanine concentrations from their pre-treatment baseline blood Phe concentrations.

 

The most common adverse events reported in the Palynziq trials included injection site reactions, joint pain, hypersensitivity reactions, headache, generalized skin reactions lasting at least 14 days, pruritus (itchy skin), nausea, dizziness, abdominal pain, throat pain, fatigue, vomiting, cough and diarrhea. Hypersensitivity reactions occurred in most patients, likely due to formation of antibodies to the product. The most serious adverse reaction in the Palynziq trials was anaphylaxis, which occurred most frequently during upward titration of the dose within the first year of treatment. Because of this serious risk, the labeling for Palynziq includes a Boxed Warning and the product is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the Palynziq REMS Program. Notable requirements of the Palynziq REMS Program include the following:

 

1. Prescribers must be certified by enrolling in the REMS program and completing training

2. Prescribers must prescribe auto-injectable epinephrine with Palynziq

3. Pharmacies must be certified with the program and must dispense only to patients who are authorized to receive Palynziq

4. Patients must enroll in the program and be educated about the risk of anaphylaxis by a certified prescriber to ensure they understand the risks and benefits of treatment with Palynziq

5. Patients must have auto-injectable epinephrine available at all times while taking Palynziq

 

The FDA granted approval of Palynziq to BioMarin Pharmaceutical Inc.

 

FDA Expands Approval of Gilenya to Treat Multiple Sclerosis in Pediatric Patients

 

Multiple Sclerosis (MS) is a chronic, inflammatory, autoimmune disease of the central nervous system that disrupts communication between the brain and other parts of the body. It is among the most common causes of neurological disability in young adults and occurs more frequently in women than men. For most people with MS, episodes of worsening function and appearance of new symptoms, called relapses or flare-ups, are initially followed by recovery periods (remissions). Over time, recovery may be incomplete, leading to progressive decline in function and increased disability. Most people with MS experience their first symptoms, like vision problems or muscle weakness, between the ages of 20 to 40. Two to five percent of people with MS have symptom onset before age 18 and estimates suggest that 8,000 to 10,000 children and adolescents in the U.S. have MS.

 

The FDA has approved Gilenya (fingolimod) to treat relapsing MS in children and adolescents age 10 years and older. This is the first FDA approval of a drug to treat MS in pediatric patients. Gilenya was first approved by the FDA in 2010 to treat adults with relapsing MS.

 

The clinical trial evaluating the effectiveness of Gilenya in treating pediatric patients with MS included 214 evaluated patients aged 10 to 17 and compared Gilenya to another MS drug, interferon beta-1a. In the study, 86% of patients receiving Gilenya remained relapse-free after 24 months of treatment, compared to 46% of those receiving interferon beta-1a. The side effects of Gilenya in pediatric trial participants were similar to those seen in adults. The most common side effects were headache, liver enzyme elevation, diarrhea, cough, flu, sinusitis, back pain, abdominal pain and pain in extremities.

 

Gilenya must be dispensed with a patient Medication Guide that describes important information about the drug’s uses and risks. Serious risks include slowing of the heart rate, especially after the first dose. Gilenya may increase the risk of serious infections. Patients should be monitored for infection during treatment and for two months after discontinuation of treatment. A rare brain infection that usually leads to death or severe disability, called progressive multifocal leukoencephalopathy (PML) has been reported in patients being treated with Gilenya. PML cases usually occur in patients with weakened immune systems. Gilenya can cause vision problems. Gilenya may increase the risk for swelling and narrowing of the blood vessels in the brain (posterior reversible encephalopathy syndrome). Other serious risks include respiratory problems, liver injury, increased blood pressure and skin cancer. Gilenya can cause harm to a developing fetus; women of child-bearing age should be advised of the potential risk to the fetus and to use effective contraception.

 

The FDA granted Priority Review and Breakthrough Therapy designation to Novartis for this indication.

 

Next Page →