Once-Monthly Buprenorphine Injection for Opioid Use Disorder

 

Improving access to prevention, treatment and recovery services, including the full range of medication-assisted treatments (MAT), is a focus of the FDA’s ongoing work to reduce the scope of the opioid crisis and one part of the U.S. Department of Health and Human Services’ Five-Point Strategy to Combat the Opioid Crisis. Opioid use disorder (OUD) is the diagnostic term used for a chronic neurobiological disease characterized by a problematic pattern of opioid use leading to significant impairment or distress. OUD includes signs and symptoms that reflect compulsive, prolonged self-administration of opioid substances for no legitimate medical purpose or, if another medical condition is present that requires opioid treatment, the opioid is used in doses far greater than the amount needed for treatment of that medical condition. MAT is a comprehensive approach that combines approved medications (currently, methadone, buprenorphine or naltrexone) with counseling and other behavioral therapies to treat patients with OUD. Regular adherence to MAT with buprenorphine reduces opioid withdrawal symptoms and the desire to use opioids, without causing the cycle of highs and lows associated with opioid misuse or abuse. At proper doses, buprenorphine also decreases the pleasurable effects of other opioids, making continued opioid abuse less attractive. According to the Substance Abuse and Mental Health Services Administration, patients receiving MAT for their OUD cut their risk of death from all causes in half.

 

Buprenorphine for the treatment of moderate-to-severe OUD is currently approved as a tablet, as an implant, or a sublingual film (absorbed under the tongue) that dissolves in the mouth. The FDA has recently approved Sublocade, the first once-monthly injectable buprenorphine product for the treatment OUD in adult patients who have initiated treatment with a transmucosal (absorbed through mucus membrane) buprenorphine-containing product. It is indicated for patients that have been on a stable dose of buprenorphine treatment for a minimum of seven days. Sublocade provides a new treatment option for patients in recovery who may value the benefits of a once-monthly injection compared to other forms of buprenorphine, such as reducing the burden of taking medication daily as prescribed (medical adherence). An independent FDA advisory committee supported the approval of Sublocade.

 

Sublocade should be used as part of a complete treatment program that includes counseling and psychosocial support. Sublocade is a drug-device combination product that utilizes buprenorphine and the Atrigel Delivery System in a pre-filled syringe. It is injected by a health care professional (HCP) under the skin (subcutaneously) as a solution, and the delivery system forms a solid deposit, or depot, containing buprenorphine. After initial formation of the depot, buprenorphine is released by the breakdown (biodegradation) of the depot. In clinical trials, Sublocade provided sustained therapeutic plasma levels of buprenorphine over the one-month dosing interval.

 

The safety and efficacy of Sublocade were evaluated in two clinical studies (one randomized controlled clinical trial and one open-label clinical trial) of 848 adults with a diagnosis of moderate-to-severe OUD who began treatment with buprenorphine/naloxone sublingual film. Once the dose was determined stable, patients were given Sublocade by injection. A response to MAT was measured by urine drug screening and self-reporting of illicit opioid use during the six-month treatment period. Results indicated that Sublocade-treated patients had more weeks without positive urine tests or self-reports of opioid use, and a higher proportion of patients had no evidence of illicit opioid use throughout the treatment period, compared to the placebo group. The most common side effects from treatment with Sublocade include constipation, nausea, vomiting, headache, drowsiness, injection site pain, itching (pruritus) at the injection site and abnormal liver function tests. The safety and efficacy of Sublocade have not been established in children or adolescents less than 17 years of age. Clinical studies of Sublocade did not include participants over the age of 65.

 

The FDA is requiring postmarketing studies to assess which patients would benefit from a higher dosing regimen, to determine whether Sublocade can be safely initiated without a dose stabilization period of sublingual buprenorphine, to assess the feasibility of administering Sublocade at a longer inter-dose interval than once-monthly and to determine a process for transitioning patients with long-term stability on a transmucosal buprenorphine dose to a monthly dose of Sublocade without the use of a higher dose for the first two months of treatment (loading dose). Sublocade has a boxed warning that provides important safety information, including the risks of intravenous self-administration. If the product were to be administered intravenously rather than subcutaneously, the solid mass could cause occlusion (blockage), tissue damage or embolus (solid material that is carried in the blood and can become lodged in a blood vessel, which can lead to death). Sublocade must be prescribed and dispensed as part of a Risk Evaluation and Mitigation Strategy (REMS) to ensure that the product is not distributed directly to patients. Sublocade will be provided to HCPs through a restricted program, administered only by HCPs in a health care setting, and will require health care settings and pharmacies that dispense Sublocade to complete an enrollment form attesting that they have procedures in place to ensure that Sublocade is dispensed only to HCPs and not directly to patients.

 

The FDA granted approval of Sublocade to Indivior Inc. and the application had Priority Review and Fast Trackdesignations.

 

Puerto Rico Related Medical Product Shortages

 

According to FDA, while Puerto Rico is making progress in its effort to recover from the devastation left by the hurricanes, it remains a long process and there’s a lot of work left to do. At the FDA, is remaining vigilant about helping address the challenges that remain. Power is being restored across the island and, importantly, some major medical product manufacturing facilities are coming back online and stabilizing their production. However, until the grid is reliably restored, many firms will continue to run on generator power or require generators as a backup and production levels will not return to their baseline levels.

 

Over the last few weeks, FDA has been addressing the IV saline products shortage, which was exacerbated by Hurricane Maria. FDA has been closely working with one supplier, Baxter, to help them restore production operations in their Puerto Rico facilities. FDA also approved IV solution products from Fresenius Kabi and Laboratorios Grifols to mitigate the shortage, and both of those companies have been working to increase production of saline products. Thanks to steps like these, FDA now believes that the shortage situation related to IV saline products will improve by the end of 2017. While FDA has made progress on this front, unfortunately there continue to be drug shortage issues that are of serious concern to the agency. In addition to FDA’s ongoing concerns related to IV saline products, FDA is also are particularly focused on the shortage of amino acids for injection. This product is of critical need for patients, including children and infants, who are not able to eat and need to receive their nutrition intravenously. Like with saline, an ongoing amino acid short supply situation was worsened by Hurricane Maria’s impact on Puerto Rican drug manufacturing facilities that manufacture this product.

 

Most notably, the hurricane disrupted Baxter’s amino acids production facilities in Puerto Rico; Baxter is one of the largest manufacturers of this product serving the U.S. market. In order to help mitigate this shortage, the FDA has worked with Baxter to facilitate the temporary importation of amino acids for pediatric and adult formulations of IV amino acids from Baxter facilities in the United Kingdom and Italy. FDA is also working with other manufacturers of amino acids to increase supplies to address the shortage, including ICU Medical and B. Braun. ICU Medical had experienced manufacturing delays, but now plans to return to the market soon, which will further help address the shortage. FDA continues to work closely with federal and Puerto Rican authorities to address the needs of manufacturers on the island for power and other resources. These efforts have been focused on the needs of patients — to prevent potential shortages of medically important products where possible, and help ensure that any shortages that do occur are mitigated as quickly as possible. FDA does understand the burden and stress drug shortages have on patients, health care providers and hospitals. FDA is monitoring approximately 90 medical products manufactured on Puerto Rico (which includes biologics, devices and drugs) that are important to patients. Mitigating medical product shortages will require a sustained effort by industry, the agency and other partners as we work with manufacturers to return to production levels that adequately meet the needs of patients.

 

FDA Launches Comprehensive Regenerative Medicine Policy Framework

 

The FDA has announced a comprehensive policy framework for the development and oversight of regenerative medicine products, including novel cellular therapies. The framework, which is outlined in a suite of four guidance documents, builds upon the FDA’s existing risk-based regulatory approach to more clearly describe what products are regulated as drugs, devices, and/or biological products. Further, two of the guidance documents propose an efficient, science-based process for helping to ensure the safety and effectiveness of these therapies, while supporting development in this area. The suite of guidance documents also defines a risk-based framework for how the FDA intends to focus its enforcement actions against those products that raise potential significant safety concerns. This proposed framework is intended to balance the agency’s commitment to safety with mechanisms to drive further advances in regenerative medicine so innovators can bring new, effective therapies to patients as quickly and safely as possible. The policy also delivers on important provisions of the 21st Century Cures Act.

 

The framework includes two final guidance documents and two draft guidance documents.

 

New Final Guidance Documents

 

The two final guidance documents clarify the FDA’s interpretation of the risk-based criteria manufacturers use to determine whether a product is subject to the FDA’s premarket review. The first guidance provides greater clarity around when cell and tissue-based products would be excepted from the established regulations if they are removed from and implanted into the same individual within the same surgical procedure and remain in their original form. The second final guidance helps stakeholders better understand how existing regulatory criteria apply to their products by clarifying how the agency interprets the existing regulatory definitions “minimal manipulation“ and “homologous use.“

 

As this field advances, the FDA has noted that there are a growing number of regenerative medicine products subject to FDA premarket authorization. These guidance documents will help explain how the FDA will provide a risk-based framework for its oversight. The policy framework defines how we intend to take action against unsafe products while facilitating continued innovation of promising technologies. To accomplish this goal, the guidance document has clarified the FDA’s view of “minimal manipulation“ and “homologous use.“ These are two concepts that are defined in current regulation to establish the legal threshold for when a product is subject to the FDA’s premarket approval requirements. By further clarifying these terms in the final guidance, the FDA is applying a modern framework for its oversight. Under the new policy, in order to allow manufacturers of products time to comply with the requirements, for the first 36 months following issuance of the final guidance document the FDA intends to exercise enforcement discretion for certain products that are subject to the FDA’s premarket review under the existing regulations, but are not currently meeting these requirements. The FDA does not intend to exercise such enforcement discretion for those products that pose a potential significant safety concern. Going forward, the FDA will apply a risk-based approach to enforcement, taking into account how products are being administered as well as the diseases and conditions for which they are being used. This risk-based approach allows product manufacturers time to engage with the FDA, as to determine if they need to submit a marketing authorization application and, if so, submit their application to the FDA for approval.

 

New Draft Guidance Documents

 

The two draft guidances provide important information to help spur development and access to innovative regenerative therapies. The first draft guidance, which builds off the regenerative medicine provisions in the 21st Century Cures Act, addresses how the FDA intends to simplify and streamline its application of the regulatory requirements for devices used in the recovery, isolation, and delivery of regenerative medicine advanced therapies (RMATs), including combination products. The guidance specifies that devices intended for use with a specific RMAT may, together with the RMAT, be considered to comprise a combination product.

 

The second draft guidance describes the expedited programs that may be available to sponsors of regenerative medicine therapies, including the new Regenerative Medicine Advanced Therapy (RMAT) designation created by the 21st Century Cures Act, Priority Review, and Accelerated Approval. In addition, the guidance describes the regenerative medicine therapies that may be eligible for RMAT designation – including cell therapies, therapeutic tissue engineering products, human cell and tissue products, and combination products using any such therapies or products, as well as gene therapies that lead to a durable modification of cells or tissues (including genetically modified cells).

 

Both draft guidance documents will have 90-day comment periods.

 

First Treatment Approved for Certain Patients with Erdheim-Chester Disease

 

Erdheim-Chester Disease (ECD) is a slow-growing blood cancer that originates in the bone marrow, and causes an increased production of histiocytes, a type of white blood cell. Excess histiocytes can result in tumors infiltrating many organs and tissues throughout the body, including the heart, lungs, brain and others. ECD is estimated to affect 600 to 700 patients worldwide. Approximately 54% of patients with ECD have the BRAF V600 mutation. Patients with ECD also have very limited life expectancies.

 

The FDA has expanded the approval of Zelboraf (vemurafenib) to include the treatment of certain adult patients with ECD. Zelboraf is indicated to treat patients whose cancer cells have the BRAF V600 mutation. This product was first approved in 2011 to treat certain patients with melanoma that harbor the BRAF V600E mutation. This is the first FDA-approved treatment for ECD.

 

Zelboraf is a kinase inhibitor that works by blocking certain enzymes that promote cell growth. The efficacy of Zelboraf for the treatment of ECD was studied in 22 patients with BRAF-V600-mutation positive ECD. The trial measured the percent of patients who experienced a complete or partial reduction in tumor size (overall response rate). In the trial, 11 patients (50%) experienced a partial response and 1 patient (4.5%) experienced a complete response. Common side effects of Zelboraf in patients with ECD include joint pain (arthralgia); small, raised bumps (maculo-papular rash); hair loss (alopecia); fatigue; change in the heart’s electrical activity (prolonged QT interval) and skin growths (papilloma). Severe side effects of Zelboraf include the development of new cancers (skin cancer, squamous cell carcinoma or other cancers), growth of tumors in patients with BRAF wild-type melanoma, hypersensitivity reactions (anaphylaxis and DRESS syndrome), severe skin reactions (Stevens-Johnson Syndrome and toxic epidermal necrolysis), heart abnormalities (QT prolongation), liver damage (hepatotoxicity), photosensitivity, severe reactions in the eye (uveitis), immune reactions after receiving radiation treatment (radiation sensitization and radiation recall), kidney failure and thickening of tissue in the hands and feet (Dupuytren’s contracture and plantar fascial fibromatosis). Zelboraf can also 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 for this indication. Zelboraf 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 Zelboraf to Hoffman-LaRoche, Inc.

 

Mutual Recognition of Manufacturing Facilities

 

Some drugs approved in the U.S. are either fully manufactured overseas or made in the U.S. but contain some foreign ingredients. All drugs approved in the U.S., regardless of where they are made, must comply with applicable U.S. regulations. One way the FDA oversees drug manufacturing is by routinely inspecting domestic and foreign drug manufacturing plants for compliance with manufacturing standards that assure quality and product label requirements.

 

The FDA has determined that it will recognize eight European drug regulatory authorities as capable of conducting inspections of manufacturing facilities that meet FDA requirements. The eight regulatory authorities found to be capable are those located in: Austria, Croatia, France, Italy, Malta, Spain, Sweden and the United Kingdom. This achievement marks an important milestone to successful implementation and operationalization of the amended Pharmaceutical Annex to the 1998 U.S.-European Union (EU) Mutual Recognition Agreement (MRA) that enables U.S. and EU regulators to utilize each other’s good manufacturing practice inspections of pharmaceutical manufacturing facilities.

 

According to FDA, beginning November 1, it will take the unprecedented and significant step forward in realizing the key benefits of the Mutual Recognition Agreement with its European counterparts in that FDA will now rely on the inspectional data obtained by these eight regulatory agencies. FDA added that the progress made so far puts it on track to meet our goal of completing all 28 capability assessments in the EU by July 2019.

 

In June 2017, the European Commission determined that the FDA “has the capability, capacity and procedures in place to carry out GMP inspections at a level equivalent to the EU.“ The completion of these capability assessments enables the FDA and the EU to avoid duplication of drug inspections and allows regulators to devote more resources to other manufacturing facilities in countries where there may be greater risk. Ultimately, this prioritization of inspections will help identify potential drug quality problems more quickly and prevent poor quality drugs from entering the U.S. market.

 

Robotic Surgery Clearance

 

The FDA has cleared the Senhance System, a new robotically-assisted surgical device (RASD) that can help facilitate minimally invasive surgery. RASD, sometimes referred to as robotic surgery, is one type of computer-assisted surgical system. RASD enables the surgeon to use computer and software technology to control and move surgical instruments through one or more tiny incisions in the patient’s body (laparoscopic surgery) in a variety of surgical procedures or operations. The benefits of RASD technology may include its ability to facilitate minimally invasive surgery and assist with complex tasks in confined areas of the body. The device, however, is not actually a true robot because it cannot perform surgery without direct human control.

 

The design of the Senhance System allows surgeons to sit at a console unit or cockpit that provides a 3-D high-definition view of the surgical field and allows them to control three separate robotic arms remotely. The end of each arm is equipped with surgical instruments that are based on traditional laparoscopic instrument designs. The system also includes unique technological characteristics: force feedback, which helps the surgeon “feel“ the stiffness of tissue being grasped by the robotic arm; eye-tracking, which helps control movement of the surgical tools and laparoscopic-type controls similar to traditional surgical equipment.

 

The Senhance System is intended to assist in the accurate control of laparoscopic instruments for visualization and endoscopic manipulation of tissue including grasping, cutting, blunt and sharp dissection, approximation, ligation, electrocautery, suturing, mobilization and retraction in laparoscopic colorectal surgery and laparoscopic gynecological surgery. The system is for use on adult patients by trained physicians in an operating room environment.

 

The manufacturer conducted a clinical study of 150 patients undergoing various gynecological operations with the Senhance System. Clinical outcomes were compared to those described in eight peer-reviewed research publications involving more than 8,000 gynecological operations performed in real-world settings (real-world evidence) using another RASD. In addition, the manufacturer submitted Senhance System operative results involving 45 patients undergoing colorectal procedures in a real-world setting and compared the results to those from peer-reviewed research publications describing the real-world device experience. The FDA concluded that these study data, supported by real-world evidence, along with performance testing under simulated use and worst-case scenario conditions, demonstrated the substantial equivalence of the Senhance System to the da Vinci Si IS3000 device for gynecological and colorectal procedures.

 

The Senhance System was reviewed through the premarket clearance (510(k)) pathway. A 510(k) notification is a premarket submission made by device manufacturers to the FDA to demonstrate that the new device is substantially equivalent to a legally marketed predicate device.

 

The FDA granted clearance of the Senhance System to TransEnterix Surgical Inc.

 

FDA Approves CAR-T Cell Therapy to Treat Adults with Certain Types of Large B-Cell Lymphoma

 

Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin lymphoma (NHL) in adults. NHLs are cancers that begin in certain cells of the immune system and can be either fast-growing (aggressive) or slow-growing. Approximately 72,000 new cases of NHL are diagnosed in the U.S. each year, and DLBCL represents approximately one in three newly diagnosed cases.

 

The FDA has approved Yescarta (axicabtagene ciloleucel), a cell-based gene therapy, to treat adult patients with certain types of large B-cell lymphoma who have not responded to or who have relapsed after at least two other kinds of treatment. Yescarta, a chimeric antigen receptor (CAR) T cell therapy, is the second gene therapy approved by the FDA and the first for certain types of non-Hodgkin lymphoma (NHL).

 

According to FDA, this approval marks another milestone in the development of a whole new scientific paradigm for the treatment of serious diseases, and that in just several decades, gene therapy has gone from being a promising concept to a practical solution to deadly and largely untreatable forms of cancer. FDA added that it will soon release a comprehensive policy to address how we plan to support the development of cell-based regenerative medicine. That policy will also clarify how we will apply our expedited programs to breakthrough products that use CAR-T cells and other gene therapies.

 

Yescarta is approved for use in adult patients with large B-cell lymphoma after at least two other kinds of treatment failed, including DLBCL, primary mediastinal large B-cell lymphoma, high grade B-cell lymphoma and DLBCL arising from follicular lymphoma. Yescarta is not indicated for the treatment of patients with primary central nervous system lymphoma. Each dose of Yescarta is a customized treatment created using a patient’s own immune system to help fight the lymphoma. The patient’s T-cells, a type of white blood cell, are collected and genetically modified to include a new gene that targets and kills the lymphoma cells. Once the cells are modified, they are infused back into the patient. The safety and efficacy of Yescarta were established in a multicenter clinical trial of more than 100 adults with refractory or relapsed large B-cell lymphoma. The complete remission rate after treatment with Yescarta was 51%.

 

Treatment with Yescarta has the potential to cause severe side effects. It carries a boxed warning for cytokine release syndrome (CRS), which is a systemic response to the activation and proliferation of CAR-T cells causing high fever and flu-like symptoms, and for neurologic toxicities. Both CRS and neurologic toxicities can be fatal or life-threatening. Other side effects include serious infections, low blood cell counts and a weakened immune system. Side effects from treatment with Yescarta usually appear within the first one to two weeks, but some side effects may occur later. Because of the risk of CRS and neurologic toxicities, Yescarta is being approved with a risk evaluation and mitigation strategy (REMS), which includes elements to assure safe use (ETASU). The FDA is requiring that hospitals and their associated clinics that dispense Yescarta be specially certified. As part of that certification, staff involved in the prescribing, dispensing or administering of Yescarta are required to be trained to recognize and manage CRS and nervous system toxicities. Also, patients must be informed of the potential serious side effects and of the importance of promptly returning to the treatment site if side effects develop.

 

To further evaluate the long-term safety, the FDA is also requiring the manufacturer to conduct a post-marketing observational study involving patients treated with Yescarta.

 

The FDA granted Yescarta Priority Review and Breakthrough Therapy designations. Yescarta also received Orphan Drug designation, which provides incentives to assist and encourage the development of drugs for rare diseases. The Yescarta application was reviewed using a coordinated, cross-agency approach. The clinical review was conducted by the FDA’s Oncology Center of Excellence, while CBER conducted all other aspects of review and made the final product approval determination.

 

The FDA granted approval of Yescarta to Kite Pharma, Inc.

 

Expanded Access: FDA Describes Efforts to Ease Application Process

 

The following was extracted from FDA Voice and posted on October 3, 2017.

 

FDA has a long history of supporting patient access to investigational new treatments. This includes working with drug and device companies through the clinical trial process that may lead to FDA approval of the treatment. FDA also offer expanded access programs that provide investigational drugs and devices to patients with serious conditions (generally prior to product approval), when there is no therapeutic alternative.

 

Each year, FDA receives over 1,000 applications for the treatment of patients through expanded access, also known as compassionate use, and the agency authorizes the vast majority (about 99%). FDA recognizes that time is critical for these seriously ill patients who do not have alternative therapies, and who cannot take part in a clinical trial of an investigational therapy. Submissions are usually authorized quickly, often in a matter of days. In the case of emergencies, FDA will typically provide authorization over the phone in a matter of hours. In an effort to eliminate potential hurdles that might delay or even discourage applications, FDA streamlined the expanded access process by introducing a new application form which a physician may use to request expanded access for their patient. Form FDA 3926 reduced the number of required information fields and attachments, and is estimated to take only 45 minutes for a physician to complete. Before expanded access can occur, the drug company must decide whether or not to provide the product. FDA cannot require a manufacturer to provide a product.

 

FDA is lifting another potential burden for physicians who apply to FDA to use an investigational drug to treat their patient. Prior to treating a patient under expanded access, the physician must obtain approval from the Institutional Review Board (IRB) at their facility. This is an important step to protect the rights, safety and well-being of human subjects in clinical research – but assembling the full board may cause delays because it may not routinely meet. As part of a plan to simplify the process for physicians seeking access to an investigational product to treat their patient, FDA has announced that just one IRB member – the chair or another appropriate person – can now approve the treatment. Dr. Gottlieb, FDA Commissioner, believes the simplified IRB process will facilitate access while still protecting patients.

 

More simplifications and clarifications are also in the pipeline. FDA has seen some reluctance among companies to provide investigational drugs for expanded access. This may have been due, in part, to uncertainty about how data for adverse events that occur during treatment under expanded access are viewed by FDA. Companies have voiced concerns that any apparent negative effects might jeopardize the product’s development. FDA recognizes that patients receiving expanded access are usually treated outside of a controlled clinical trial setting. As a result, they may have more advanced disease than clinical trial participants, be receiving other drugs at the same time, and have other diseases. FDA recognizes that these factors make it more difficult to determine the cause an adverse reaction. To clarify how adverse event data in these circumstances are viewed, FDA has updated the guidance for industry entitled, ?Expanded Access to Investigational Drugs for Treatment Use: Questions and Answers’ (questions 25 and 26). The guidance clarifies that suspected adverse reactions must be reported “only if there is evidence to suggest a causal relationship between the drug and the adverse event.“ Dr. Gottlieb is confident these changes will help to address recent issues raised by the Government Accountability Office (GAO), which said that FDA “should further clarify how adverse event data are used.“ FDA is still evaluating the GAO recommendations to identify other possible ways to respond to their concerns.

 

FDA is committed to helping patients and physicians fully understand the expanded access process. Dedicated staff in the Office of Health and Constituent Affairs and CDER’s Office of Communications, Division of Drug Information, already assist physicians and patients in navigating this system. FDA issued three final guidance documents last year to clarify and explain the process. This past July, FDA collaborated with the Reagan-Udall Foundation, patient advocacy groups, the pharmaceutical industry, and other federal agencies to launch a new online tool called the Expanded Access Navigator. This includes a directory where companies can submit public links to their expanded access policies, the criteria used by companies to determine whether to make a drug available through expanded access, and contact information. The directory offers patients and physicians a helpful starting point for researching available investigational therapies. In addition, FDA is working with the Reagan-Udall Foundation to expand this new tool. FDA is pleased to announce that Reagan-Udall will expand its portfolio to include FDA’s Rare Disease Program, with the goal of promoting more expanded access to treatments for rare disorders.

 

Real World Evidence (RWE) and Real World Data (RWD)

 

On August 30, 2017, the U.S. Food and Drug Administration released a final guidance document on the Use of Real-World Evidence to Support Regulatory Decision-Making for Medical Devices. This guidance clarifies how the agency determines whether real-world data may be sufficient for use in regulatory decisions, without changing the evidentiary standards FDA uses to make those decisions. It clarifies how FDA plans to evaluate real-world data to determine whether it may be sufficiently relevant and reliable for various regulatory decisions, and it also clarifies when an Investigational Device Exemption (IDE) may be needed to collect and use real-world data for purposes of determining the safety and effectiveness of a device.

 

Real-world data, which relate to patient health status and/or the delivery of health care routinely collected from a variety of sources, can provide powerful insight into the benefits and risks of medical devices, including how they are used by health care providers and patients. This guidance is a cornerstone of FDA’s strategic priority to build a national evaluation system for health technology (NEST).

 

On October 10, 2017 from 1:00-2:30pm EST, the FDA will hold a webinar about this guidance. 

Registration is not necessary.

 

To hear the presentation and ask questions: Dial: 800-779-8625; passcode: 7388850 | International: 1-210-234-0098; passcode: 7388850

To view the slide presentation during the webinar:

More information about this webinar or our complete webinar series can be found on the Medical Device Webinars and Stakeholder Calls webpage.

 

Following the conclusion of the webinar, you will be able to complete a brief survey about your FDA medical device webinar experience. The survey can be found at www.fda.gov/CDRHWebinar immediately following the conclusion of the live webinar.

 

If you have general questions about this guidance, please contact the Division of Industry and Consumer Education (DICE) in the Center for Devices and Radiological Health (CDRH) at 1-800-638-2041 or 301-796-7100 or dice@fda.hhs.gov.

 

Making Advances Against Sickle Cell Disease

 

The following was abstracted from FDA Voice posted on September 26, 2017

 

The medical definition of sickle cell disease – a group of inherited red blood cell disorders caused by abnormal hemoglobin, called hemoglobin S or sickle hemoglobin, in red blood cells – does not come close to describing the condition from the patient’s perspective. Sickle cell disorders have devastating effects on patients and their families. Patients often experience recurrent episodes of excruciating pain, or sickle cell crisis, debilitating fatigue, infections, cognitive disorders, strokes, a life-threatening condition called acute chest syndrome, and damage to their vital organs, tissues, and bones. In some patients, the disease may trigger frequent and very painful sickle cell crises that require hospitalization. In others, it may cause less frequent and milder attacks. Although mortality during childhood has improved progressively, the life expectancy among individuals with sickle cell disease in the United States is on average 30 years less than the general population.

 

Sickle cell is a rare disease. According to the Centers for Disease Control and Prevention, about 1 of every 365 African-Americans and about 1 out of every 16,300 Hispanic-Americans are born with sickle cell disease. In addition, more than 2 million people carry the sickle cell gene that enables them to possibly pass the disease on to their children. Today, bone marrow transplantation offers the only potential cure for this disorder; but finding a donor is difficult and the procedure has serious risk.

 

As Sickle Cell Awareness Month comes to a close this September, FDA reports on how much must be done to help patients in need and educate others on sickle cell disease – and also to recognize progress and hope for a better future.

 

In July, FDA approved Endari (L-glutamine oral powder) to reduce the severe complications from the blood disorder in patients age 5 years and older. Endari is only the second FDA-approved treatment for this disorder and the first since hydroxyurea was approved nearly 20 years ago. Studies showed that patients taking Endari experienced fewer trips to the emergency room and fewer hospitalizations for sickle cell pain than those given a placebo. They also had fewer occurrences of acute chest syndrome. Common side effects include constipation, nausea, headache, abdominal pain, cough, pain in the extremities, back pain, and chest pain.

 

FDA continues to work with all interested parties in improving the lives of patients with sickle cell disease. In February 2014, FDA held the first ever federal meeting with patients as part of our Patient Focused Drug Development program. A highlight was learning what symptoms bothered patients the most in their daily lives – the sort of information that can help inform the development and use of patient reported outcomes. And for the past several years, FDA clinical review staff has organized meetings to facilitate drug development in sickle cell disease. During these events, academic researchers, clinicians and FDA have engaged in an interactive discussion on trial design, potential endpoints, and patient reported outcomes.

 

Sickle cell disease describes a group of inherited red blood cell disorders caused by abnormal hemoglobin, the protein that carries oxygen throughout the body. Normal hemoglobin moves easily through blood vessels, but sickle hemoglobin can be crescent or sickle shaped, which causes it to stick on vessel walls, blocking or stopping the flow of blood. (Source, FDA Blog)

 

It is not entirely clear why progress in developing treatments for sickle cell disease has been slow. One challenge has been the multi-faceted nature of sickle cell disease as well as difficulty in defining biochemical endpoints and targets of clinical benefit in clinical trials. But there is hope. Since 2010, FDA has seen a rise in the number of industry meetings, clinical trial development and investigational new drug (IND) submissions for sickle cell disease (required when companies want to conduct clinical trials of an investigational new drug), which may qualify for an expedited approval program known as Fast Track. Patient-reported outcome measures are being incorporated into clinical trials for new products. Currently 143 clinical trials (on Clinicaltrials.gov) are recruiting patients studying drug interventions, gene therapy, behavioral treatment and diagnostic testing in both adults and children.

 

While the Center for Drug Evaluation and Research (CDER) work to encourage drug development, other efforts are underway to make bone marrow transplantation accessible to more patients as well as utilizing gene editing which can provide a permanent cure for sickle cell disease by correcting the sickle mutation in the stem cells. FDA knows there is much more work to be done, but FDA says it is proud to say during this Sickle Cell Awareness Month, that we are part of a dynamic team and remain committed to promoting the development of safe and effective treatments for this blood disorder.

 

For more information, please visit: The FDA Encourages New Treatments for Sickle Cell Disease

 

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