FDA Approves Treatment for Chronic Graft Versus Host Disease

 

Chronic graft versus host disease (cGVHD) is a life-threatening condition that can occur in patients after they receive a stem cell transplant from blood or bone marrow, called hematopoietic stem cell transplantation (HSCT). HSCT is used to treat certain blood or bone marrow cancers. cGVHD occurs when cells from the stem cell transplant attack healthy cells in a patient’s tissues. Symptoms of cGVHD can occur in the skin, eyes, mouth, gut, liver and lungs. The condition is estimated to occur in 30-70% of all patients who receive HSCT.

 

The FDA has expanded the approval of Imbruvica (ibrutinib) for the treatment of adult patients with chronic graft versus host disease (cGVHD) after failure of one or more treatments. This is the first FDA-approved therapy for the treatment of cGVHD. The efficacy and safety of Imbruvica for the treatment of cGVHD were studied in a single-arm trial of 42 patients with cGVHD whose symptoms persisted despite standard treatment with corticosteroids. Most patients’ symptoms included mouth ulcers and skin rashes, and more than 50% of patients had two or more organs affected by cGVHD. In the trial, 67% of patients experienced improvements in their cGVHD symptoms. In 48% of patients in the trial, the improvement of symptoms lasted for up to five months or longer.

 

Common side effects of Imbruvica in patients with cGVHD include fatigue, bruising, diarrhea, low levels of blood platelets (thrombocytopenia), muscle spasms, swelling and sores in the mouth (stomatitis), nausea, severe bleeding (hemorrhage), low levels of red blood cells (anemia) and lung infection (pneumonia). Serious side effects of Imbruvica include severe bleeding (hemorrhage), infections, low levels of blood cells (cytopenias), irregular heartbeat (atrial fibrillation), high blood pressure (hypertension), new cancers (second primary malignancies) and metabolic abnormalities (tumor lysis syndrome). Women who are pregnant or breastfeeding should not take Imbruvica because it may cause harm to a developing fetus or a newborn baby.

 

Imbruvica, a kinase inhibitor, was previously approved for certain indications in treating chronic lymphocytic leukemia, Waldenstrom’s macroglobulinemia and marginal zone lymphoma, as well as under accelerated approval status for mantle cell lymphoma.

 

The FDA granted this application Priority Review and Breakthrough Therapydesignations. Imbruvica also received Orphan Drug designation for this indication, which provides incentives to assist and encourage the development of drugs for rare diseases. The FDA granted the approval of Imbruvica to Pharmacyclics LLC.

 

FDA Announces New Steps to Empower Consumers and Advance Digital Healthcare

 

The following was extracted from FDA Voice, by: Scott Gottlieb, M.D.

 

When people think about personalized medicine, they often think of genetic testing and sequencing of the human genome. But the concept of personalized medicine is much broader. It includes the re-imagination of healthcare delivery. It includes empowering consumers to take more control of their own healthcare information to make better informed decisions about their medical care and healthy living. This opportunity is enabled by a new technological paradigm of digital health tools, like apps, that enable consumers to have more active engagement and access to real-time information about their health and their activities. These tools allow consumers and providers to supersede the traditional, physical constraints of healthcare delivery and exploit the opportunities offered by mobile technology.

 

Historically, healthcare has been slow to implement disruptive technology tools that have transformed other areas of commerce and daily life. One factor that’s been cited, among many, is the regulation that accompanies medical products. But momentum toward a digital future in healthcare is advancing. Not all of these tools are subject to FDA regulation.

 

Last week, FDA announced, as part of our broader Medical Innovation Access Plan, a new component focused on digital health innovation – the formal launch of our Pre-Cert for Software Pilot Program. This new program embraces the principle that digital health technologies can have significant benefits to patients’ lives and to our healthcare system by facilitating prevention, treatment, and diagnosis; and by helping consumers manage chronic conditions outside of traditional healthcare settings. At the same time, FDA’s Center for Devices and Radiological Health (CDRH) is publishing its Digital Health Innovation Action Plan to provide details and timelines for an integrated approach to digital health technology and the implementation of the 21st Century Cures Act. By doing this, FDA is telling consumers and the digital health industry how FDA will establish clear and consistent expectations for the products FDA regulates. The challenge FDA faced in the past is determining how to best regulate these non-traditional medical tools with the traditional approach to medical product review. Now, FDA will envision and seek to develop through the Pre-Cert for Software Pilot a new and pragmatic approach to digital health technology. The method, of course, must recognize the unique characteristics of digital health products and the marketplace for these tools, so FDA can continue to promote innovation of high-quality, safe, and effective digital health devices.

 

FDA’s feels that its traditional approach to medical devices is not well suited to these products, and it needs to make sure its approach to innovative products with continual updates and upgrades is efficient and that it fosters, not impedes, innovation. Recognizing this, and understanding that the potential of digital health is nothing short of revolutionary, FDA is working toward establishing an appropriate approach that’s closely tailored to this new category of products. FDA needs a regulatory framework that accommodates the distinctive nature of digital health technology, its clinical promise, the unique user interface, and industry’s compressed commercial cycle of new product introductions.

 

This new, voluntary pilot program will enable FDA to develop a tailored approach toward this technology by looking first at the software developer or digital health technology developer, rather than primarily at the product (as FDA currently does for traditional medical products). This pilot will help FDA establish the most appropriate criteria for standing up a firm-based pre-certification program for these new tools. The goal of this new approach is for FDA to, after reviewing systems for software design, validation and maintenance, determine whether the company meets the necessary quality standards and pre-certify the company. Pre-certified companies could submit less information to us than is currently required before marketing a new digital health tool. In some cases, pre-certified companies could not submit a premarket submission at all. In those cases, the pre-certified company could launch a new product and immediately begin post-market data collection. Pre-certified digital health companies could take advantage of this approach for certain lower-risk devices by demonstrating that the underlying software and internal processes are sufficiently reliable. The post-market data could help FDA assure that the new product remains safe and effective as well as supports new uses.

 

FDA designed the new digital health pilot program to include up to nine software firms of various sizes. Initial participants in this new pilot will range from small startups to large companies that develop both high- and low-risk software products that are devices. FDA wants to include medical product manufacturers as well as non-traditional software developers. Given the amount of attention FDA is getting, and the ongoing innovation in this space, FDA is confident that there will be strong participation in the new pilot.

 

Digital health product developers will be selected for the program based on the following:

  • The company must be in the process of developing or planning to develop a software product that meets the definition of a medical device;
  • The company must have an existing track record in developing, testing, and maintaining software products and demonstrating a culture of quality and organizational excellence measures that are tracked by Key Performance Indicators (KPI) or other similar measures;
  • And during participation of the pilot, companies must agree to:
    • Provide access to measures for developing, testing and maintaining software products and demonstrating a culture of quality and organizational excellence measures by KPI;
    • Collect real-world post-market data and provide it to FDA;
    • Meet with FDA for real-time consultation;
    • Be available for site visits from FDA officials; and,
    • Provide information about the firm’s quality management system.

 

FDA has intentionally left the initial criteria broad because this pilot is purposely designed to be inclusive and flexible. FDA wants to be able to accommodate a broad range of participants and technologies. FDA also appreciates that the experience and capabilities of a small company will be different from that of a large company and recognize that we need a pre-certification program that accommodates both.

 

The initiative will begin immediately. Starting on August 1, companies can submit a statement of interest that includes the qualities listed above, requesting participation in the pilot to FDAPre-CertPilot@fda.hhs.gov. Then, during the month of August, FDA’s Digital Health Team will evaluate submissions and select companies that reflect the broad range of software developers. A critical component is that FDA will include small and large companies, traditional and non-traditional MedTech companies, and products that range in risk. This approach will create opportunities for more dynamic entrepreneurship and competition and help continue to drive product innovation.

 

FDA expects that the first four months of the pilot will better inform FDA’s regulatory team as well as product developers. FDA will hold a public workshop in January 2018 to report on and review the initial findings. The goal is to inform product developers who are not participating in the pilot, so they can understand our process and findings, to help better inform development programs underway outside of the pilot.

 

As FDA launches its Digital Health Innovation Action Plan, FDA is aware that apps and app updates come to market every day. But the most powerful feature of this market may not be one revolutionary app but rather a combination of apps that provides consumers and providers with the information they need. This can help people better manage their chronic diseases, which could result in less trips to the doctor for checkups, or better awareness of illness, like prompts to a parent with a sick child on when they need to see a provider.

 

FDA Approves New Treatment For Sickle Cell Disease

 

Sickle cell disease is an inherited blood disorder in which the red blood cells are abnormally shaped (in a crescent, or sickle, shape). This restricts the flow in blood vessels and limits oxygen delivery to the body’s tissues, leading to severe pain and organ damage. According to the National Institutes of Health, approximately 100,000 people in the United States have sickle cell disease. The disease occurs most often in African-Americans, Latinos and other minority groups. The average life expectancy for patients with sickle cell disease in the United States is approximately 40 to 60 years.

 

The FDA has approved Endari (L-glutamine oral powder) for patients age five years and older with sickle cell disease to reduce severe complications associated with this blood disorder. The safety and efficacy of Endari were studied in a randomized trial of patients ages 5-58 years old with sickle cell disease who had two or more painful crises within the 12 months prior to enrollment in the trial. Patients were assigned randomly to treatment with Endari or placebo, and the effect of treatment was evaluated over 48 weeks. Patients who were treated with Endari experienced fewer hospital visits for pain treated with a parenterally administered narcotic or ketorolac (sickle cell crises), on average, compared to patients who received a placebo (median 3 vs. median 4), fewer hospitalizations for sickle cell pain (median 2 vs. median 3), and fewer days in the hospital (median 6.5 days vs. median 11 days). Patients who received Endari also had fewer occurrences of acute chest syndrome (a life-threatening complication of sickle cell disease) compared with patients who received a placebo (8.6 percent vs. 23.1 percent). Common side effects of Endari include constipation, nausea, headache, abdominal pain, cough, pain in the extremities, back pain and chest pain.

 

Endari received Orphan Drug designation for this use, which provides incentives to assist and encourage the development of drugs for rare diseases. In addition, development of this drug was in part supported by the FDA Orphan Products Grants Program, which provides grants for clinical studies on safety and/or effectiveness of products for use in rare diseases or conditions.

 

The FDA granted the approval of Endari to Emmaus Medical Inc.

 

FDA Unveils Plan to Eliminate Orphan Designation Backlog

 

For our last Orphan Drug Designation Request, FDA told us that there could be a 6 month review time. We did contact the Division and were told about the major backlog.

 

As authorized under the Orphan Drug Act, the Orphan Drug Designation Program provides orphan status to drugs and biologics that are defined as those intended for the safe and effective treatment, diagnosis or prevention of rare diseases, which are generally defined as diseases that affect fewer than 200,000 people in the United States. Orphan designation qualifies the sponsor of the drug for various development incentives, including tax credits for clinical trial costs, relief from prescription drug user fee if the indication is for a rare disease or condition, and eligibility for seven years of marketing exclusivity upon approval. A request for orphan designation is one step that can be taken in the drug development process and is different than the filing of a marketing application with the FDA.

 

The FDA has unveiled a strategic plan to eliminate the existing orphan designation request backlog and ensure continued timely response to all new requests for designation with firm deadlines. The agency’s Orphan Drug Modernization Plan comes a week after FDA Commissioner Scott Gottlieb committed to eliminating the backlog within 90 days and responding to all new requests for designation within 90 days of receipt during his testimony before a Senate subcommittee.

 

Currently, the FDA has about 200 orphan drug designation requests that are pending review. The number of orphan drug designation requests has steadily increased over the past five years. In 2016, the FDA’s Office of Orphan Products Development received 568 new requests for designation – more than double the number of requests received in 2012. The increased interest in the program is a positive development for those with rare diseases and under this new plan, the agency remains committed to advancing the program to ensure it can efficiently and adequately review these requests.

 

This is the first element of several efforts the FDA will undertake under its new “Medical Innovation Development Plan,“ which is aimed at ensuring that the FDA’s regulatory tools and policies are modern, risk based, and efficient. The goal of the plan is to seek ways the FDA can help facilitate the development of safe, effective and transformative medical innovations that have the potential to significantly impact disease and reduce overall health care costs. Among the elements of the plan to eliminate the backlog, the FDA will deploy a Backlog SWAT team comprised of senior, experienced reviewers with significant expertise in orphan drug designation. The team will focus solely on the backlogged applications, starting with the oldest requests. The agency will also employ a new streamlined Designation Review Template to increase consistency and efficiency of its reviews. The program will also look to collaborate within the agency’s medical product centers to create greater efficiency, including conducting joint reviews with the Office of Pediatric Therapeutics to review rare pediatric disease designation requests.

 

To ensure all future requests receive a response within 90 days of receipt, the agency will take a multifaceted approach. These efforts include, among other new steps: reorganizing the review staff to maximize expertise and improve workload efficiencies; better leveraging the expertise across the FDA’s medical product centers; and establishing a new FDA Orphan Products Council that will help address scientific and regulatory issues to ensure the agency is applying a consistent approach to regulating orphan drug products and reviewing designation requests.

 

The FDA intends to communicate around the successful elimination of the backlog by mid-September and will soon provide more information about the Medical Innovation Development Plan.

 

First Subcutaneous C1 Esterase Inhibitor to Treat Hereditary Angioedema (HAE)

 

Hereditary Angioedema (HAE), which is caused by having insufficient amounts of a plasma protein called C1-esterase inhibitor (or C1-INH), affects approximately 6,000 to 10,000 people in the U.S. People with HAE can develop rapid swelling of the hands, feet, limbs, face, intestinal tract or airway. These attacks of swelling can occur spontaneously, or can be triggered by stress, surgery or infection.

 

The FDA has approved Haegarda, the first C1 Esterase Inhibitor (Human) for subcutaneous (under the skin) administration to prevent HAE attacks in adolescent and adult patients. The subcutaneous route of administration allows for easier at-home self-injection by the patient or caregiver, once proper training is received.

 

Haegarda is a human plasma-derived, purified, pasteurized, lyophilized (freeze-dried) concentrate prepared from large pools of human plasma from U.S. donors. Haegarda is indicated for routine prophylaxis to prevent HAE attacks, but is not indicated for treatment of acute HAE attacks. The efficacy of Haegarda was demonstrated in a multicenter controlled clinical trial. The study included 90 subjects ranging in age from 12 to 72 years old with symptomatic HAE. Subjects were randomized to receive twice per week subcutaneous doses of either 40 IU/kg or 60 IU/kg, and the treatment effect was compared to a placebo treatment period. During the 16 week treatment period, patients in both treatment groups experienced a significantly reduced number of HAE attacks compared to their placebo treatment period.

 

The most common side effects included injection site reactions, hypersensitivity (allergic) reactions, nasopharyngitis (swelling of the nasal passages and throat) and dizziness. Haegarda should not be used in individuals who have experienced life-threatening hypersensitivity reactions, including anaphylaxis, to a C1-INH preparation or its inactive ingredients.

 

Haegarda received Orphan Drug designation, which provides incentives to assist and encourage the development of drugs to treat rare diseases or conditions.

 

The FDA granted approval of Haegarda to CSL Behring LLC.

 

Fostering Medical Innovation: A Plan for Digital Health Devices

 

The following was reported by Scott Gottlieb, M.D., FDA Commissioner

 

Dr. Gottlieb indicated that it is incumbent upon FDA to ensure that they have the right policies in place to promote and encourage safe and effective innovation that can benefit consumers, and adopt regulatory approaches to enable the efficient development of these technologies. By taking an efficient, risk-based approach to regulations, FDA can promote health through the creation of more new and beneficial medical technologies. FDA can also help reduce the development costs for these innovations by making sure that our own policies and tools are modern and efficient, giving entrepreneurs more opportunities to develop products that can benefit people’s lives.

 

To this end, FDA will soon be putting forward a broad initiative that is focused on fostering new innovation across our medical product centers. However, today Dr. Gottlieb is focusing on one critical aspect of this innovation initiative: A new Digital Health Innovation Plan that is focused on fostering innovation at the intersection of medicine and digital health technology. This plan will include a novel, post-market approach to how FDA intends to regulate these digital medical devices.

 

According to one estimate, last year there were 165,000 health-related apps available for smartphones. Forecasts predict that such apps would be downloaded 1.7 billion times by 2017. From mobile apps and fitness trackers to clinical decision support software, innovative digital technologies have the power to transform health care in important ways, such as:

 

1. Empowering consumers to make more and better decisions every day about their own health, monitor and manage chronic health conditions, or connect with medical professionals, using consumer-directed apps and other technologies to help people live healthier lifestyles through fitness, nutrition, and wellness monitoring;

2. Enabling better and more efficient clinical practice and decision making through decision support software and technologies to assist in making diagnoses and developing treatment options; managing, storing, and sharing health records; and managing schedules and workflow;

3. Helping to address public health crises, such as the opioid epidemic that is devastating many American communities. In fact, FDA conducted a prize competition to encourage the development of a mobile app to help connect opioid users experiencing an overdose with nearby carriers of the prescription drug naloxone for emergency treatment.

 

For these and other digital technologies to take hold and reach their fullest potential, it is critical that FDA be forward-leaning in making sure that they have implemented the right policies and regulatory tools, and communicated them clearly.In this rapidly changing environment, ambiguity regarding how FDA will approach a new technology can lead innovators to invest their time and resources in other ventures. To encourage innovation, FDA should carry out its mission to protect and promote the public health through policies that are clear enough for developers to apply them on their own. Developers should not have to seek out, on a case-by-case basis, FDA’s position on every individual technological change or iterative software development.

 

Congress has already taken a major step to advance these goals in the 21st Century Cures Act. Expanding upon policies advanced by FDA’s Center for Devices and Radiological Health (CDRH), the Act revised FDA’s governing statute to, among other things, make clear that certain digital health technologies – such as clinical administrative support software and mobile apps that are intended only for maintaining or encouraging a healthy lifestyle – generally fall outside the scope of FDA regulation. Such technologies tend to pose low risk to patients but can provide great value to the health care system. FDA, led by CDRH, is working to implement the digital health provisions of the 21st Century Cures Act and, in the coming months, will be publishing guidance to further clarify what falls outside the scope of FDA regulation and to explain how the new statutory provisions affect pre-existing FDA policies. FDA will provide guidance to clarify their position on products that contain multiple software functions, where some fall outside the scope of FDA regulation, but others do not. In addition, FDA will provide new guidance on other technologies that, although not addressed in the 21st Century Cures Act, present low enough risks that FDA does not intend to subject them to certain pre-market regulatory requirements. Greater certainty regarding what types of digital health technology is subject to regulation and regarding FDA’s compliance policies will not only help foster innovation, but also will help the agency to devote more resources to higher risk priorities.

 

In addition to these efforts, FDA has announced a new initiative. This fall, as part of a comprehensive approach to the regulation of digital health tools and in collaboration with our customers, FDA will pilot an entirely new approach toward regulating this technology. This will be the cornerstone to a more efficient, risk-based regulatory framework for overseeing these medical technologies. While the pilot program is still being developed, FDA is considering whether and how, under current authorities, they can create a third party certification program. Under this program, lower risk digital health products could be marketed without FDA premarket review and higher risk products could be marketed with a streamlined FDA premarket review. Certification could be used to assess, for example, whether a company consistently and reliably engages in high quality software design and testing (validation) and ongoing maintenance of its software products. Employing a unique pre-certification program for software as a medical device (SaMD) could reduce the time and cost of market entry for digital health technologies.

 

In addition, post-market collection of real-world data might be able to be used to support new and evolving product functions. For example, product developers could leverage real-world data gathered through the National Evaluation System for health Technology (NEST) to expedite market entry and subsequent expansion of indications more efficiently. NEST will be a federated virtual system for evidence generation composed of strategic alliances among data sources including registries, electronic health records, payer claims, and other sources. The Medical Device Innovation Consortium (MDIC), a 501(c)(3) public-private partnership, is serving as an independent coordinating center that operates NEST. In the coming weeks, MDIC will announce the establishment of a Governing Committee for the NEST Coordinating Center comprised of stakeholder representatives of the ecosystem, such as patients, health care professionals, health care organizations, payers, industry, and government. Although FDA does not own or operate NEST, they have been establishing strategic alliances among data sources to accelerate NEST’s launch with the initial version of a fully operational system anticipated by the end of 2019. Applying this firm-based approach, rather than the traditional product-based approach, combined with leveraging real-world evidence, would create market incentives for greater investment in and growth of the digital health technology industry. Such processes could enable developers to deploy new or updated software more rapidly and would help FDA to better focus its resources.

 

Through these and other steps, according to Dr. Gottlieb, FDA will help innovators navigate a new, modern regulatory process so that promising, safe and effective developments in digital health can advance more quickly and responsibly, and Americans can reap the full benefits from these innovations. These efforts are just one part of a much broader initiative that FDA is currently undertaking to advance policies that promote the development of safe and effective medical technologies that can help consumers improve their health. FDA’s goal is to make sure that FDA has the most modern and efficient regulatory approaches when it comes to evaluating new, beneficial technologies. Scott Gottlieb, M.D., is Commissioner of the U.S. Food and Drug Administration

 

FDA Requests Removal of Opana ER for Risks Related to Abuse

 

The FDA has requested that Endo Pharmaceuticals remove its opioid pain medication, reformulated Opana ER (oxymorphone hydrochloride), from the market. After careful consideration, the agency is seeking removal based on its concern that the benefits of the drug may no longer outweigh its risks. This is the first time the agency has taken steps to remove a currently marketed opioid pain medication from sale due to the public health consequences of abuse.

 

The FDA’s decision is based on a review of all available post-marketing data, which demonstrated a significant shift in the route of abuse of Opana ER from nasal to injection following the product’s reformulation. Injection abuse of reformulated Opana ER has been associated with a serious outbreak of HIV and hepatitis C, as well as cases of a serious blood disorder (thrombotic microangiopathy). This decision follows a March 2017 FDA advisory committee meeting where a group of independent experts voted 18-8 that the benefits of reformulated Opana ER no longer outweigh its risks.

 

Opana ER was first approved in 2006 for the management of moderate-to-severe pain when a continuous, around-the-clock opioid analgesic is needed for an extended period of time. In 2012, Endo replaced the original formulation of Opana ER with a new formulation intended to make the drug resistant to physical and chemical manipulation for abuse by snorting or injecting. While the product met the regulatory standards for approval, the FDA determined that the data did not show that the reformulation could be expected to meaningfully reduce abuse and declined the company’s request to include labeling describing potentially abuse-deterrent properties for Opana ER. Now, with more information about the risks of the reformulated product, the agency is taking steps to remove the reformulated Opana ER from the market.

 

The FDA has requested that the company voluntarily remove reformulated Opana ER from the market. Should the company choose not to remove the product, the agency intends to take steps to formally require its removal by withdrawing approval. In the interim, the FDA is making health care professionals and others aware of the particularly serious risks associated with the abuse of this product. The FDA will continue to examine the risk-benefit profile of all approved opioid analgesic products and take further actions as appropriate as a part of our response to this public health crisis.

 

First Drug Approved to Specifically Treat Giant Cell Arteritis

 

Giant cell arteritis is a form of vasculitis, a group of disorders that results in inflammation of blood vessels. This inflammation causes the arteries to narrow or become irregular, impeding adequate blood flow. In giant cell arteritis, the vessels most involved are those of the head, especially the temporal arteries (located on each side of the head). For this reason, the disorder is sometimes called temporal arteritis. However, other blood vessels, including large ones like the aorta, can become inflamed in giant cell arteritis. Standard treatment involves high doses of corticosteroids that are tapered over time.

 

The FDA has expanded the approved use of subcutaneous Actemra (tocilizumab) to treat adults with giant cell arteritis. This new indication provides the first FDA-approved therapy, specific to this type of vasculitis. The efficacy and safety of subcutaneous (injected under the skin) Actemra for giant cell arteritis were established in a double-blind, placebo-controlled study with 251 patients with giant cell arteritis. The primary efficacy endpoint was the proportion of patients achieving sustained remission from Week 12 through Week 52. Sustained remission was defined as the absence of symptoms of giant cell arteritis, normalization of inflammatory laboratory tests, and tapering the use of prednisone (a steroid drug). Results showed a greater proportion of patients receiving subcutaneous Actemra with standardized prednisone regimens achieved sustained remission from Week 12 through Week 52, as compared to patients receiving placebo with standardized prednisone regimens. The cumulative prednisone dose was also lower in treated patients with Actemra relative to placebo.

 

The overall safety profile observed in the Actemra treatment groups was generally consistent with the known safety profile of Actemra. Actemra carries a Boxed Warning for serious infections. Patients treated with Actemra who develop a serious infection should stop that treatment until the infection is controlled. Live vaccines should be avoided during treatment with Actemra. Actemra should be used with caution in patients at increased risk of gastrointestinal perforation. Hypersensitivity reactions, including anaphylaxis and death, have occurred. Laboratory monitoring is recommended due to potential consequences of treatment-related changes in neutrophils (type of white blood cell), platelets, lipids and liver function tests.

 

Subcutaneous Actemra was previously approved for the treatment of moderate to severely active rheumatoid arthritis. Intravenous Actemra was also previously approved for the treatment of moderate to severely active rheumatoid arthritis, systemic juvenile idiopathic arthritis and polyarticular juvenile idiopathic arthritis. Intravenous administration is not approved for giant cell arteritis.

 

The FDA granted this application a Breakthrough Therapy designation and a Priority Review. Actemra is sold by Hoffman La Roche, Inc.

 

HUGE: FDA Approves First Cancer Treatment for Any Solid Tumor With a Specific Genetic Biomarker

 

EDITOR’S NOTE: THIS APPROVAL IS BEYOND HUGE AS WE CAN NOW START TREATING THE ROOT CAUSE OF DISEASES RATHER THAN THEIR ORGAN (e.g. Colon Cancer)

 

MSI-H and dMMR tumors contain abnormalities that affect the proper repair of DNA inside the cell. Tumors with these biomarkers are most commonly found in colorectal, endometrial and gastrointestinal cancers, but also less commonly appear in cancers arising in the breast, prostate, bladder, thyroid gland and other places. Approximately 5% of patients with metastatic colorectal cancer have MSI-H or dMMR tumors.

 

The FDA has granted accelerated approval to a treatment for patients whose cancers have a specific genetic biomarker. This is the first time the agency has approved a cancer treatment based on a common biomarker rather than the location in the body where the tumor originated.

 

Keytruda (pembrolizumab) is indicated for the treatment of adult and pediatric patients with unresectable or metastatic solid tumors that have been identified as having a biomarker referred to as microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR). This indication covers patients with solid tumors that have progressed following prior treatment and who have no satisfactory alternative treatment options and patients with colorectal cancer that has progressed following treatment with certain chemotherapy drugs.

 

According to Richard Pazdur, M.D., acting director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research and director of the FDA’s Oncology Center of Excellence. “This is an important first for the cancer community, since until now, the FDA has approved cancer treatments based on where in the body the cancer started – for example, lung or breast cancers. We have now approved a drug based on a tumor’s biomarker without regard to the tumor’s original location.“

 

Keytruda works by targeting the cellular pathway known as PD-1/PD-L1 (proteins found on the body’s immune cells and some cancer cells). By blocking this pathway, Keytruda may help the body’s immune system fight the cancer cells. The FDA previously approved Keytruda for the treatment of certain patients with metastatic melanoma, metastatic non-small cell lung cancer, recurrent or metastatic head and neck cancer, refractory classical Hodgkin lymphoma, and urothelial carcinoma.

 

Keytruda was approved for this new indication using 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 is required to verify and describe anticipated clinical benefits of Keytruda, and the sponsor is currently conducting these studies in additional patients with MSI-H or dMMR tumors.

 

The safety and efficacy of Keytruda for this indication were studied in patients with MSI-H or dMMR solid tumors enrolled in one of five uncontrolled, single-arm clinical trials. In some trials, patients were required to have MSI-H or dMMR cancers, while in other trials, a subgroup of patients were identified as having MSI-H or dMMR cancers by testing tumor samples after treatment began. A total of 15 cancer types were identified among 149 patients enrolled across these five clinical trials. The most common cancers were colorectal, endometrial and other gastrointestinal cancers.

 

The review of Keytruda for this indication was based on the percentage of patients who experienced complete or partial shrinkage of their tumors (overall response rate) and for how long (durability of response). Of the 149 patients who received Keytruda in the trials, 39.6% had a complete or partial response, and for 78% of those patients, the response lasted for six months or more. Common side effects of Keytruda include fatigue, itchy skin (pruritus), diarrhea, decreased appetite, rash, fever (pyrexia), cough, difficulty breathing (dyspnea), musculoskeletal pain, constipation and nausea. Keytruda can cause serious conditions known as immune-mediated side effects, including inflammation of healthy organs such as the lungs (pneumonitis), colon (colitis), liver (hepatitis), endocrine glands (endocrinopathies) and kidneys (nephritis). Complications or death related to allogeneic hematopoietic stem cell transplantation after using Keytruda has occurred. Patients who experience severe or life-threatening infusion-related reactions should stop taking Keytruda. Women who are pregnant or breastfeeding should not take Keytruda because it may cause harm to a developing fetus or newborn baby. The safety and effectiveness of Keytruda in pediatric patients with MSI-H central nervous system cancers have not been established.

 

FDA Expands Approved Use of Kalydeco to Treat Additional Mutations of Cystic Fibrosis

 

Cystic fibrosis is a rare disease that affects about 30,000 people in the United States and affects the cells that produce mucus, sweat and digestive juices. These secreted fluids are normally thin and slippery due to the movement of sufficient ions (chloride) and water in and out of the cells. People with the progressive disease have a defective cystic fibrosis transmembrane conductance regulator (CFTR) gene that can’t regulate the movement of ions and water, causing the secretions to become sticky and thick. The secretions build up in the lungs, digestive tract and other parts of the body leading to severe respiratory and digestive problems, as well as other complications such as infections and diabetes.

 

The FDA has expanded the approved use of Kalydeco (ivacaftor) for treating cystic fibrosis. The approval triples the number of rare gene mutations that the drug can now treat, expanding the indication from the treatment of 10 mutations, to 33. The agency based its decision, in part, on the results of laboratory testing, which it used in conjunction with evidence from earlier human clinical trials. The approach provides a pathway for adding additional, rare mutations of the disease, based on laboratory data.

 

Results from an in vitro cell-based model system have been shown to reasonably predict clinical response to Kalydeco. When additional mutations responded to Kalydeco in the laboratory test, researchers were thus able to extrapolate clinical benefit demonstrated in earlier clinical trials of other mutations. This resulted in the addition of gene mutations for which the drug is now indicated. Kalydeco, available as tablets or oral granules taken two times a day with fat-containing food, helps the protein made by the CFTR gene, function better and as a result, improves lung function and other aspects of cystic fibrosis, including weight gain. If the patient’s genotype is unknown, an FDA-cleared cystic fibrosis mutation test should be used to detect the presence of a CFTR mutation followed by verification with bi-directional sequencing when recommended by the mutation test instructions for use.

 

Kalydeco is indicated for patients aged 2 and older who have one mutation in the CFTR gene that is responsive to drug treatment based on clinical and/or in vitro (laboratory) data. The expanded indication will affect another 3 percent of the cystic fibrosis population, impacting approximately 900 patients. Kalydeco serves as an example of how successful patient-focused drug development can provide greater understanding about a disease. For example, the Cystic Fibrosis Foundation maintains a 28,000-patient registry, including genetic data, which it makes available for research.

 

Common side effects of Kalydeco include headache; upper respiratory tract infection (common cold) including sore throat, nasal or sinus congestion, or runny nose; stomach (abdominal) pain; diarrhea; rash; nausea; and dizziness. Kalydeco is associated with risks including elevated transaminases (various enzymes produced by the liver) and pediatric cataracts. Co-administration with strong CYP3A inducers (e.g., rifampin, St. John’s wort) substantially decreases exposure of Kalydeco, which may diminish effectiveness, and is therefore not recommended.

 

Kalydeco is manufactured for Boston-based Vertex Pharmaceuticals Inc.

 

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