Next Generation Sequencing-Based Tests (NGS)

 

Next generation sequencing (NGS) works by looking at a person’s DNA to detect genomic variations that may determine whether a person has or is at risk of developing a genetic disease and, in certain cases, may help to inform treatment decisions. Unlike traditional diagnostics that typically detect chemical changes associated with a single disease or condition, NGS can look at millions of DNA changes in a single test to help determine the cause of a person’s disease or condition. Availability of these types of tests plays an important role in the advancement of the field of precision medicine.

 

The FDA has finalized two guidances to drive the efficient development of NGS technology. The guidances provide recommendations for designing, developing, and validating tests that use NGS, and will play an important role in the continued advancement of individualized, genetic-based medicine. The first guidance, “Use of Public Human Genetic Variant Databases to Support Clinical Validity for Genetic and Genomic-Based In Vitro Diagnostics,“ describes an approach where test developers may rely on clinical evidence from FDA-recognized public databases to support clinical claims for their tests and help provide assurance of the accurate clinical evaluation of genomic test results. The guidance describes how product developers can use these databases to support the clinical validation of NGS tests that they are developing. These public databases may include resources like ClinGen, which is maintained by the National Institutes of Health (NIH). Using FDA-recognized databases will provide test developers with an efficient path for marketing clearance or approval of a new test.

 

The second guidance, “Considerations for Design, Development, and Analytical Validation of Next Generation Sequencing (NGS)-Based In Vitro Diagnostics (IVDs) Intended to Aid in the Diagnosis of Suspected Germline Diseases,“ provides recommendations for designing, developing, and validating NGS-based tests used to diagnose individuals with suspected genetic diseases. It describes what the FDA would look for in premarket submissions to determine a test’s analytical validity, including how well the test detects the presence or absence of a particular genomic change. According to FDA, since information about genetic variants is generally stored in a manner that is not publicly accessible, the release of the FDA’s final guidance should help to provide an even more efficient path to market by encouraging data sharing, as well as the accumulation in public databases of evidence supporting the clinical validity of genomic tests.

 

Issuance of these final guidances is based on extensive feedback from the public and stakeholders who are developing NGS-based technologies, and the guidances serve as a continuation of the FDA’s work creating regulatory efficiencies in the development and review of NGS tests. In 2017, the FDA took several actions to streamline the development and review of a variety of genetic-based tests – authorizing a third-party option for conducting reviews NGS tumor profiling tests and making clearance recommendations to FDA, as well as outlining standardized development criteria for carrier screening tests to allow for their marketing without prior agency review. FDA also established such criteria for genetic health risk tests and proposed to allow their marketing after a one-time agency review. As NGS technologies continue to evolve, the FDA remains dedicated to adapting our regulatory review capabilities and leveraging our authorities to the fullest extent in order to make innovative and accurate testing technologies available to patients as efficiently as possible.

 

The Voice of the Patient

 

The following is based on a press release from Dr. Scott Gottlieb, FDA Commissioner.

 

Benefit-risk assessment is at the heart of what FDA does to ensure that Americans have access to medical products that are safe, effective and meet their needs. But FDA is also deeply aware that serious chronic illnesses aren’t monolithic. Patient perception of the benefits and risks of different treatment options can vary based on the stage of the disease, the age of onset, alternative therapies available to treat the disease (if any) and whether a novel therapy improves a patient’s ability to function normally, slows the rate of disease progression or impacts other aspects of a patient’s quality of life.

 

A 45-year-old father of two who is diagnosed with aggressive prostate cancer may have very different goals than an 80-year-old man diagnosed with the same disease. To address these realities, FDA will continue to work in close partnership with patients to incorporate their experience into FDA’s benefit-risk assessments. First-hand knowledge of living with a serious illness – communicated in science-based terms that patients value and understand – is integral to facilitating the successful development of safe and effective products that can deliver meaningful benefits in each disease, or disease state.

 

Today there are many more tools to measure these patient benefits – including wearable devices, medical apps and even machine-learning programs. These tools can bring a better understanding of how patients experience their illness, including how it affects their day-to-day feeling or functioning and how a given treatment may impact the course of that illness. Tools for capturing the patient experience may be quantitative or qualitative, but they are transforming nearly every aspect of medical product development. Patients can teach all of us about the benefits that matter most to them and the risks that they are most concerned about. Patients are, rightly so, becoming the driving force of the medical research enterprise.

 

Structured and Transparent Benefit-Risk Assessments

 

FDA’s ongoing work to enhance their benefit-risk assessment and communication in the human drug review process began in 2013 as part of the Prescription Drug User Fee Act (PDUFA) V. The priority to enhance benefit-risk assessment has continued with new efforts begun in 2017, as part of PDUFA VI and further expanded under 21st Century Cures. Implementing these key pieces of legislation is improving clarity and consistency in communicating the reasoning behind the FDA’s drug regulatory decisions. It’s also helping integrate the patient’s perspective into drug development and regulatory decision-making.

FDA has issued an update to their implementation plan, titled “Benefit-Risk Assessment in Drug Regulatory Decision-Making.“ This document provides an overview of the steps the FDA has taken since 2013 to enhance benefit-risk assessment in human drug review, which included implementation of the FDA’s Benefit-Risk Framework into our drug regulatory review processes and documentation. This document also provides a roadmap for enhancing the Benefit-Risk Framework, working toward a goal of providing guidance by June 2020 that articulates the FDA’s decision-making context and framework for benefit-risk assessment. This forthcoming guidance will also outline how patient experience data and related information can be used to inform benefit-risk assessment.

 

In order for a drug or biologic product to be approved, the FDA conducts a comprehensive analysis of all available data to determine if the drug is effective and that its expected benefits outweigh its potential risks. This assessment is fundamental to our regulatory process. The goal of the FDA’s Benefit-Risk Framework is to improve the clarity and consistency in communicating the reasoning behind drug regulatory decisions, and ensure that the FDA reviewers’ detailed assessments can be readily understood in the broader context of patient care and public health. The structured framework also helps drug sponsors and other external stakeholders better understand the factors that contribute to the FDA’s decision-making process when evaluating new drugs, including drugs under development. A standard Benefit-Risk Framework will also better ensure that the patient community can continue to engage effectively with the agency, and help FDA improve how it evaluates benefits and risks from the patient’s perspective. The Benefit-Risk Framework has been applied in FDA reviews of novel drugs and biologics over the past few years, and FDA is now using it more broadly.

 

Incorporating Patient Voice into Benefit-Risk Assessments

 

The Benefit-Risk Framework recognizes that when FDA reviewers conduct a benefit-risk assessment, they consider not only the submitted evidence related to the benefit and risk and effects reported in clinical studies, but also, importantly, the “clinical context“ of the disease. This context encompasses two major considerations: 1) an analysis of the disease condition, including the severity of the condition; and 2) the degree of unmet medical need. As part of this work, the FDA recognizes a need to learn about the clinical context more comprehensively and directly from the perspective of the patients who live with the disease and their caregivers. After conducting patient-focused drug development meetings in over 20 disease areas, the FDA has concluded that patient input can: 1) inform the clinical context and provide insights to frame the assessment of benefits and risk; and 2) provide a direct source of evidence regarding the benefits and risks, if methodologically-sound data collection tools could be developed and used within clinical studies of an investigational therapy. The FDA is now developing guidance to enable more widespread development of such patient experience data to inform regulatory decision-making, as part of our implementation of PDUFA VI and 21st Century Cures. Other efforts to more systematically incorporate patients’ experiences and perspectives include:

 

1. Hosting patient-focused drug development public meetings to advance a more systematic way of gathering patients’ perspectives on their conditions and available treatments;

2. Encouraging patient stakeholders and others to conduct their own externally-led, patient-focused drug development meetings;

3. Providing patients, caregivers, advocates and others with more channels to provide meaningful input into drug development and regulatory decision-making, and to more easily access information provided by others; and

4. Launching pilot programs – and advancing policies, in collaboration with the medical community – that help foster the design of clinical trials that place less burden on patients.

 

The benefit-risk implementation plan issued today is part of the FDA’s ongoing commitment to advancing its mission of protecting and promoting public health. It marks another important step forward in increasing transparency of FDA decisions as well as streamlining the process by which FDA obtains input from the patient and stakeholder communities. In the battle against disease, engaged and informed patients are our best allies and one of the greatest resources.

FDA Expands Approval of Blincyto for Treatment of B-Cell Precursor ALL in Patients Who Have a Certain Risk Factor for Relapse

 

B-cell precursor ALL is a rapidly progressing type of cancer in which the bone marrow makes too many B-cell lymphocytes, an immature type of white blood cell. The National Cancer Institute estimates that approximately 5,960 people in the United States will be diagnosed with ALL this year and approximately 1,470 will die from the disease.

 

The FDA has granted accelerated approval to Blincyto (blinatumomab) to treat adults and children with B-cell precursor acute lymphoblastic leukemia (ALL) who are in remission but still have minimal residual disease (MRD). MRD refers to the presence of cancer cells below a level that can be seen under the microscope. In patients who have achieved remission after initial treatment for this type of ALL, the presence of MRD means they have an increased risk of relapse. According to FDA, this is the first FDA-approved treatment for patients with MRD-positive ALL, and because patients who have MRD are more likely to relapse, having a treatment option that eliminates even very low amounts of residual leukemia cells may help keep the cancer in remission longer.

 

Blincyto works by attaching to CD19 protein on the leukemia cells and CD3 protein found on certain immune system cells. Bringing the immune cell close to the leukemia cell allows the immune cells to attack the leukemia cells better. The FDA first approved Blincyto under accelerated approval in December 2014 for the treatment of Philadelphia chromosome (Ph)-negative relapsed or refractory positive B-cell precursor ALL. Full approval for this indication was granted in July 2017, and at that time, the indication was also expanded to include patients with Philadelphia chromosome-positive ALL.

 

The efficacy of Blincyto in MRD-positive ALL was shown in a single-arm clinical trial that included 86 patients in first or second complete remission who had detectable MRD in at least 1 out of 1,000 cells in their bone marrow. Efficacy was based on achievement of undetectable MRD in an assay that could detect at least one cancer cell in 10,000 cells after one cycle of Blincyto treatment, in addition to the length of time that the patients remained alive and in remission (hematological relapse-free survival). Overall, undetectable MRD was achieved by 70 patients. Over half of the patients remained alive and in remission for at least 22.3 months.

 

The side effects of Blincyto when used to treat MRD-positive B-cell precursor ALL are consistent with those seen in other uses of the drug. Common side effects include infections (bacterial and pathogen unspecified), fever (pyrexia), headache, infusion related reactions, low levels of certain blood cells (neutropenia, anemia), febrile neutropenia (neutropenia and fever) and low levels of platelets in the blood (thrombocytopenia). Blincyto carries a boxed warning alerting patients and health care professionals that some clinical trial participants had problems with low blood pressure and difficulty breathing (cytokine release syndrome) at the start of the first treatment, experienced a short period of difficulty with thinking (encephalopathy) or other side effects in the nervous system. Serious risks of Blincyto include infections, effects on the ability to drive and use machines, inflammation in the pancreas (pancreatitis), and preparation and administration errors – instructions for preparation and administration should closely be followed. There is a risk of serious adverse reactions in pediatric patients due to benzyl alcohol preservative; therefore, the drug prepared with preservative free saline should be used for patients weighing less than 22 kilograms.

 

This new indication for Blincyto was approved under the accelerated approval pathway, under which the FDA may approve drugs for serious conditions where there is unmet medical need and a drug is shown to have certain effects that are reasonably likely to predict a clinical benefit to patients. Further study in randomized controlled trials is required to verify that achieving undetectable MRD with Blincyto improves survival or disease-free survival in patients with ALL.

 

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

 

Device Cleared That Senses Optimal Time to Check Intraocular Pressure

 

Elevated IOP is often associated with the optic nerve damage that is characteristic of glaucoma, the leading cause of vision loss that affects an estimated 3 million Americans.. Many patients have no symptoms until significant vision has been lost, and this loss is irreversible. intraocular pressure (IOP) varies throughout the day and may not be abnormally high when the patient is at an eye care professional’s office having an eye exam. For example, it is common for IOP to increase during sleep when the patient is lying down.

 

The FDA has allowed marketing of a one-time use contact lens that may help practitioners identify the best time of day to measure a patient’s intraocular pressure (IOP). The Triggerfish has a sensor embedded in a soft silicone contact lens that detects tiny changes or fluctuations in an eye’s volume. The device is worn for a maximum of 24 hours, transmitting data wirelessly from the sensor to an adhesive antenna worn around the eye. A portable data recorder worn by the patient receives information from the antenna and can transfer the data via Bluetooth to the clinician’s computer, which shows the range of time during the day the pressure of the eye may be increasing. The device does not actually measure IOP and is not intended to be a diagnostic tool.

 

The Triggerfish is indicated for use in adults age 22 and older under the direction and supervision of a health care professional. Clinical data supporting the marketing authorization of the Triggerfish included several studies of the safety and tolerability of the contact lenses and the effectiveness of the device measurement. The effectiveness of the device was demonstrated by showing an association between the Triggerfish device output and IOP fluctuation. The most common temporary side effects were pressure marks from the contact lens, ocular hyperemia (red eyes) and punctate keratitis (irritation of the cornea). The FDA reviewed the data for the Triggerfish through the de novo premarket review pathway, a regulatory pathway for some low- to moderate-risk medical devices that are not substantially equivalent to an already legally-marketed device.

 

The Triggerfish is manufactured by Sensimed AG of Lausanne, Switzerland.

 

Screening Test to Help Reduce Risk of Transfusion-Transmitted Babesiosis

 

Babesiosis is caused by Babesia parasites that are transmitted by Ixodes scapularis ticks, also known as blacklegged or deer ticks. B. microti is the main species that causes infection in the U.S. There are about 1,000 to 2,000 cases of babesiosis reported in the U.S. each year, with the majority reported from states in the Northeast and upper Midwest. Babesia can also be transmitted by transfusion of blood or blood components collected from an infected donor. The vast majority of people infected with B. microti do not have symptoms and are never diagnosed. Some people develop flu-like symptoms, such as fever, headache and body aches. The U.S. Centers for Disease Control and Prevention (CDC) warns that for certain people, especially those with a weak immune system, it can be a severe, life-threatening disease and that while bloodborne transmission of babesiosis is thought to be uncommon, it is the most frequently reported transfusion-transmitted parasitic infection in the U.S. and remains an important concern.

 

The FDA approved the Imugen Babesia microti Arrayed Fluorescent Immunoassay (AFIA), for the detection of antibodies to Babesia microti (B. microti) in human plasma samples, and the Imugen Babesia microti Nucleic Acid Test (NAT), for the detection of B. microti DNA in human whole blood samples. These tests are intended to be used as donor screening tests on samples from individual human donors, including volunteer donors of whole blood and blood components, as well as living organ and tissue donors.

 

The investigational use of Babesia donor testing has been in place since August 2012 in selected Babesia endemic areas under investigational new drug applications (INDs). The use of the investigational tests has resulted in the removal of a significant number of infected units from the blood supply. The data collected from this testing and from additional studies performed by the manufacturer prevented the release of hundreds of potentially infectious donations and demonstrated that the tests are effective in screening donors for B. microti infection. The tests approved today are not intended for use in the diagnosis of babesiosis infections.

 

These applications were granted Priority Review, under which the FDA’s goal is to take action on an application within six months where the agency determines that the product, if approved, would significantly improve the safety or effectiveness of treating, diagnosing or preventing a serious condition.

 

There currently is no FDA guidance for the testing of donor samples for Babesia. However, the FDA is planning to issue draft guidance with recommendations for reducing the risk of transfusion-transmitted babesiosis later this year.

 

The approval of the Imugen Babesia microti AFIA and NAT tests was granted to Oxford Immunotec, Inc. Both assays are in-house tests that can only be performed at the Norwood, Massachusetts facility.

 

FDA Has Approved the Smallest Mechanical Heart Valve in the World

 

Heart valve disease occurs if one or more of the four heart valves, which direct the flow of blood through the heart, fail to function properly. In pediatric patients, a malfunctioning heart valve is often the result of a congenital heart defect at birth. Each year, more than 35,000 babies in the U.S. are born with congenital heart defects, some of which will require heart valve surgery and, potentially, replacement heart valve surgery.

 

The FDA has expanded the approval of a heart valve to include a size small enough to be used in newborn pediatric patients to treat heart defects. Specifically, the agency approved the Masters Series Mechanical Heart Valve with Hemodynamic Plus (HP) Sewing Cuff to include the 15-mm valve size, making it the smallest mechanical heart valve approved in the world. Prior to this approval, there have been limited replacement heart valve options available because of the patients’ small size. The Masters Series 15-mm HP valve represents an important treatment option for these patients.

 

The Master Series Mechanical Heart Valve is a rotatable, bileaflet (two-leaflet) valve designed for implantation in the aortic or mitral position. The bileaflet design consists of two semi-circular discs that open and close in response to blood pressure changes during the heartbeat, similar to a patient’s own valve. The Masters Series Mechanical Heart Valve was first approved in 1995 for patients with a diseased, damaged or malfunctioning aortic or mitral heart valve. The device is also approved for use in replacing previously implanted aortic or mitral prosthetic heart valves. The approval expands the range of valve sizes available, providing smaller patients another treatment option.

 

The FDA evaluated clinical data from a single-arm study of 20 pediatric patients with serious heart failure ranging in age from 1.5 weeks to 27 months at the time of mitral valve implant. The data showed that one year after the implant procedure, the probability of survival was 69.3% and the probability of not experiencing a valve-related adverse event was 66.8%. Serious valve-related adverse events observed during the study through one-year follow-up included blood clots in the device and bleeding in the brain. Anticoagulation (blood thinning) therapy may be necessary after the procedure, to prevent clotting on the device, which can increase the risk of bleeding. As a caution, the Master Series Mechanical Heart Valve should not be used by patients unable to tolerate anticoagulation therapy.

 

The FDA granted approval of the Master Series Heart Valve to St. Jude Medical.

 

FDA Warns of Fraudulent and Unapproved Flu Products

 

As part of the FDA’s ongoing efforts to protect consumers from health fraud, the agency is reminding consumers to be wary of unapproved products claiming to prevent, treat or cure influenza, or flu. This year’s severe flu season raises new concerns about the potential for consumers to be lured into buying unproven flu treatments, and even worse, buying counterfeit antivirals online from websites that appear to be legitimate online pharmacies. As the flu continues to make people sick – and even cause deaths – unscrupulous actors may also be taking advantage of unsuspecting consumers by promoting their fraudulent products that have not been reviewed by the FDA to be safe and effective. The FDA is warning consumers to be alert, and try and steer clear of fraudulent flu products, which may be found online or in retail stores. FDA is advising consumers on some of the telltale signs to look for when trying to spot flu products that may be fraudulent. People who are sick with flu-like symptoms and those who are at high risk of serious flu complications should see a health care professional as soon as possible to see if they should be treated with antiviral drugs.

 

Consumers should be aware that there are no legally marketed over-the-counter (OTC) drugs to prevent or cure the flu. However, there are legal OTC products to reduce fever and to relieve muscle aches, congestion and other symptoms typically associated with the flu. Products sold online are fraudulent if they claim to prevent, treat or cure the flu, and have not been evaluated by the FDA for that intended use. These flu claims may indicate that an OTC product is fraudulent:

 

– reduces severity and length of the flu;

– boosts your immunity naturally without a flu shot;

– safe and effective alternative to the flu vaccine;

– prevents catching the flu;

– effective treatment for the flu;

– faster recovery from the flu; or

– supports your body’s natural immune defenses to fight off the flu.

 

Health fraud scams waste money, lead to delays in getting a proper diagnosis and treatment, and may even lead to more serious injuries or death. The FDA routinely warns the public about health scams and has recently taken action against companies promoting and selling unproven treatments for cancer, opioid addiction and other illnesses. However, there are numerous unapproved and potentially unsafe products that continue to be sold directly to consumers in part because companies or individuals can move their marketing operations to new websites. Online pharmacies present another opportunity for scammers to take advantage of unsuspecting consumers. Online pharmacies may claim to sell prescription antiviral drugs, such as Tamiflu, at reduced prices or without a prescription. The FDA advises consumers to avoid purchasing products making such claims. Beware of online pharmacies that:

 

– allow you to buy prescription medicine without a prescription from your health care provider;

– do not have a U.S. state-licensed pharmacist available to answer your questions;

– offer very low prices that seem too good to be true; or

– are located outside of the U.S. or ship worldwide.

 

These pharmacies often sell medicines that can be dangerous because they may:

 

– have too much or too little of the active ingredient you need to treat your disease or condition;

– not contain the right active ingredient; or

– contain wrong or other harmful ingredients.

 

Legitimate online pharmacies exist, but so do many websites that look like professional and legitimate pharmacies, but are actually fraudulent. The FDA recommends consumers buy prescription drugs from their local pharmacy or only through an online pharmacy that requires a valid prescription from a doctor or other authorized health care professional and is licensed by the state board of pharmacy (or equivalent state agency) where the patient is located.

 

FDA Clears First Blood Test to Aid in the Evaluation of Concussion in Adults

 

According to the U.S. Centers for Disease Control and Prevention, in 2013 there were approximately 2.8 million TBI-related emergency department visits, hospitalizations and deaths in the U.S. Of these cases, TBI contributed to the deaths of nearly 50,000 people. TBI is caused by a bump, blow or jolt to the head or a penetrating head injury that disrupts the brain’s normal functioning. Its severity may range from mild to severe, with 75% of TBIs that occur each year being assessed as mTBIs or concussions. A majority of patients with concussion symptoms have a negative CT scan. Potential effects of TBI can include impaired thinking or memory, movement, sensation or emotional functioning. Most patients with a suspected head injury are examined using a neurological scale, called the 15-point Glasgow Coma Scale, followed by a computed tomography or CT scan of the head to detect brain tissue damage, or intracranial lesions that may require treatment. However, a majority of patients evaluated for mTBI/concussion do not have detectable intracranial lesions after having a CT scan. Availability of a blood test for concussion would help health care professionals determine the need for a CT scan in patients suspected of having mTBI and help prevent unnecessary neuroimaging and associated radiation exposure to patients.

 

The FDA has cleared for marketing the first blood test in adults to evaluate mild traumatic brain injury (mTBI), commonly referred to as concussions. The FDA reviewed and authorized for marketing the Banyan Brain Trauma Indicator in fewer than 6 months as part of its Breakthrough Devices Program. The Brain Trauma Indicator works by measuring levels of proteins, known as UCH-L1 and GFAP, that are released from the brain into blood and measured within 12 hours of head injury. Levels of these blood proteins after mTBI/concussion can help predict which patients may have intracranial lesions visible by CT scan and which won’t. Being able to predict if patients have a low probability of intracranial lesions can help health care professionals in their management of patients and the decision to perform a CT scan. Test results can be available within 3 to 4 hours.

 

The FDA evaluated data from a multi-center, prospective clinical study of 1,947 individual blood samples from adults with suspected mTBI/concussion and reviewed the product’s performance by comparing mTBI/concussion blood tests results with CT scan results. The Brain Trauma Indicator was able to predict the presence of intracranial lesions on a CT scan 97.5% of the time and those who did not have intracranial lesions on a CT scan 99.6% of the time. These findings indicate that the test can reliably predict the absence of intracranial lesions and that health care professionals can incorporate this tool into the standard of care for patients to rule out the need for a CT scan in at least one-third of patients who are suspected of having mTBI.

 

The Brain Trauma Indicator was reviewed under the FDA’s De Novo premarket review pathway, a regulatory pathway for some low- to moderate-risk devices that are novel and for which there is no prior legally marketed device.

 

The FDA is permitting marketing of the Brain Trauma Indicator to Banyan Biomarkers.

FDA Expands Approval of Imfinzi to Reduce the Risk of Progressing NSCLC

 

Lung cancer is the leading cause of cancer death in the United States, with an estimated 222,500 new diagnoses and 155,870 deaths in 2017, according to the National Cancer Institute at the National Institutes of Health. The most common type of lung cancer, non-small cell lung cancer (NSCLC), occurs when cancer cells form in the tissues of the lung. Stage III NSCLC means tumors have spread to nearby lymph nodes or into other parts of the body near the lungs.

 

The FDA has approved Imfinzi (durvalumab) for the treatment of patients with stage III (NSCLC whose tumors are not able to be surgically removed (unresectable) and whose cancer has not progressed after treatment with chemotherapy and radiation (chemoradiation). According to FDA, this is the first treatment approved for stage III unresectable NSCLC to reduce the risk of the cancer progressing, when the cancer has not worsened after chemoradiation. For patients with stage III lung cancer that cannot be removed surgically, the current approach to prevent progression is chemoradiation. Although a small number of patients may be cured with the chemoradiation, the cancer may eventually progress. Patients now have an approved therapy that has been shown to keep the cancer from progressing for a longer time after chemoradiation.

 

Imfinzi targets the PD-1/PD-L1 pathway (proteins found on the body’s immune cells and some cancer cells). By blocking these interactions, Imfinzi may help the body’s immune system attack cancer cells. Imfinzi was previously granted accelerated approval in 2017 for the treatment of certain patients with locally advanced or metastatic bladder cancer. The approval of Imfinzi for the treatment of stage III, unresectable NSCLC was based on a randomized trial of 713 patients whose cancer had not progressed after completing chemotherapy and radiation. The trial measured the length of time the tumors did not have significant growth after starting treatment with Imfinzi or a placebo (progression-free survival). The median progression-free survival for patients taking Imfinzi was 16.8 months compared to 5.6 months for patients receiving a placebo. In addition, the sponsor has agreed to a post-marketing commitment to provide additional information from their study to the FDA about how long patients lived following treatment with Imfinzi after chemotherapy and radiation (overall survival).

 

Common side effects of Imfinzi in patients with stage III unresectable NSCLC include cough, fatigue, inflammation in the lungs (pneumonitis/radiation pneumonitis), upper respiratory tract infections, difficulty breathing and rash. Serious risks of Imfinzi include immune-mediated side effects, where the body’s immune system attacks healthy cells or organs, such as the lungs (pneumonitis), liver (hepatitis), colon (colitis), hormone-producing glands (endocrinopathies) and kidneys (nephritis). Other serious side effects of Imfinzi include infection and infusion-related reactions. Imfinzi can cause harm to a developing fetus; women should be advised of the potential risk to the fetus and to use effective contraception.

 

The FDA granted this application Priority Review and Breakthrough Therapy designations. Imfinzi is marketed by AstraZeneca.

 

New Treatment for Certain Digestive Tract Cancers

 

Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) can be present in the pancreas and in different parts of the gastrointestinal tract such as the stomach, intestines, colon and rectum. It is estimated that approximately one out of 27,000 people are diagnosed with GEP-NETs per year.

 

The FDA has approved Lutathera (lutetium Lu 177 dotatate) for the treatment adult patients with somatostatin receptor-positive GEP-NETs. Lutathera is a radioactive drug that works by binding to a part of a cell called a somatostatin receptor, which may be present on certain tumors. After binding to the receptor, the drug enters the cell allowing radiation to cause damage to the tumor cells. This is the first time a radioactive drug, or radiopharmaceutical, has been approved for the treatment of GEP-NETs.

 

The approval of Lutathera was supported by two studies. The first was a randomized clinical trial in 229 patients with a certain type of advanced somatostatin receptor-positive GEP-NET. Patients in the trial either received Lutathera in combination with the drug octreotide or octreotide alone. The study measured the length of time the tumors did not grow after treatment (progression-free survival). Progression-free survival was longer for patients taking Lutathera with octreotide compared to patients who received octreotide alone. This means the risk of tumor growth or patient death was lower for patients who received Lutathera with octreotide compared to that of patients who received only octreotide.

 

The second study was based on data from 1,214 patients with somatostatin receptor-positive tumors, including GEP-NETS, who received Lutathera at a single site in the Netherlands. Complete or partial tumor shrinkage was reported in 16% of a subset of 360 patients with GEP-NETs who were evaluated for response by the FDA. Patients initially enrolled in the study received Lutathera as part of an expanded access program. Expanded access is a way for patients with serious or immediately life-threatening diseases or conditions who lack therapeutic alternatives to gain access to investigational drugs for treatment use.

 

Common side effects of Lutathera include low levels of white blood cells (lymphopenia), high levels of enzymes in certain organs (increased GGT, AST and/or ALT), vomiting, nausea, high levels of blood sugar (hyperglycemia) and low levels of potassium in the blood (hypokalemia). Serious side effects of Lutathera include low levels of blood cells (myelosuppression), development of certain blood or bone marrow cancers (secondary myelodysplastic syndrome and leukemia), kidney damage (renal toxicity), liver damage (hepatotoxicity), abnormal levels of hormones in the body (neuroendocrine hormonal crises) and infertility. Lutathera can cause harm to a developing fetus; women should be advised of the potential risk to the fetus and to use effective contraception. Patients taking Lutathera are exposed to radiation. Exposure of other patients, medical personnel, and household members should be limited in accordance with radiation safety practices.

 

Lutathera was granted Priority Review, under which the FDA’s goal is to take action on an application within six monthswhere the agency determines that the drug, if approved, would significantly improve the safety or effectiveness of treating, diagnosing or preventing a serious condition. Lutathera 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 Lutathera to Advanced Accelerator Applications.

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