201 0 obj <> endobj The FDA instituted its Accelerated Approval Program to allow for earlier approval of drugs that treat serious conditions, and fill an unmet medical need based on a surrogate endpoint. Importance The US Food and Drug Administration (FDA) grants accelerated approval according to surrogate measures of numerous drug indications for serious or life-threatening illnesses such as infectious diseases and cancer. 2023 Cooley LLP and Cooley (UK) LLP. S8;wo3>_i"6tLk(, p0i50r 5Tggw`>AL&%?^S.S;9),Yf4]\ J4'Lyp N;H%db_KKpO%[D\(P'j/Q3yJTf*\$C;4Ab 1!Y@TXHX *%`)&(I%,j}F2:>Iz!bp Before sharing sensitive information, make sure you're on a federal government site. A surrogate endpoint is a marker, such as a laboratory measurement, radiographic image, physical sign or other measure that is thought to predict clinical benefit but is not itself a measure of clinical benefit. Subbiah V, Wirth LJ, Kurzrock R, Pazdur R, Beaver JA, Singh H, Mehta GU. Additionally, the Medicaid and CHIP Payment and Access Commission last year provided recommendations to Congress to strike a balance between addressing state concerns . Madrigal expects to complete full submission of the New Drug Application in July 2023 CONSHOHOCKEN, Pa., June 30, 2023 (GLOBE NEWSWIRE) -- Madrigal Pharmaceuticals, Inc. (NASDAQ:MDGL), a clinical . For fatal diseases without available treatments, the risk of more significant side effects may be acceptable. The drug company will still need to conduct studies to confirm that tumor shrinkage actually predicts that patients will live longer. The FDA developed the Accelerated Approval Program almost 30 years ago. Q: Are specific endpoints used to supportaccelerated approval in oncology? One such section addresses recent criticism of the FDA around the accelerated approval pathway. A Priority Review designation means FDAs goal is to take action on an application within 6 months. A: Yes. An accelerated approval from FDA means the agency concluded that the drug is safe and effective for the particular indication for use while acknowledging that there is uncertainty whether the surrogate endpoint will correlate to an ultimate clinical benefit for that indication [ 3 ]. Accelerated approval allows for earlier access to drugs and biologics based on initial evidence of safety and effectiveness, and while confirmatory studies required to verify clinical benefit are ongoing. Accelerated approvals also must meet the same statutory standard for approval but may use a surrogate endpoint reasonably likely to predict clinical benefit instead of a more time-consuming clinical benefit endpoint. Teclistamab was granted accelerated approval by the FDA on October 25, 2022 based on a phase 2 clinical trial that showed an overall response rate of 62% and the median overall survival of participants was increased to 18.3 months 10. For example, instead of having to wait to learn if a drug actually extends survival for cancer patients, the FDA may approve a drug based on evidence that the drug shrinks tumors, because tumor shrinkage is considered reasonably likely to predict a real clinical benefit. The agency often turns to the accelerated approval pathway for oncology drugs because of the serious and life-threatening nature of cancer, and because intermediate clinical end points such as progression-free survival or overall response rate are likely predictors of clinical benefit. Speedier drug approvals hit slowdown as FDA faces scrutiny FDA strongly recommends that the confirmatory trial(s) be well underway if not fully enrolled at the time of accelerated approval. FDORA amends the prohibited act provisions of the Federal Food, Drug, and Cosmetic Act6 to include new prohibitions covering the failure to conduct with due diligence any post-approval study required by an accelerated approval and the failure to submit timely progress reports for post-approval studies. By continuing on our website, you agree to our use of the cookie for statistical and personalization purpose. At the time of accelerated approval, postmarketing requirements are agreed to by the company and FDA. The portfolio of cancer drugs, many for people lacking other options, has rapidly grown to currently comprise more than a third of novel drug approvals. The FDA also can withdraw an accelerated approval if the sponsor fails to conduct the post-approval studies with due diligence, the studies fail to verify the predicted effect or demonstrate that the product is safe or effective under the conditions of use, or if the sponsor disseminates false or misleading promotional material. The program was codified into law under the Food and Drug Safety and Innovation Act (FDASIA) in 2012. Although FDORA establishes multiple new requirements with respect to accelerated approval, the text of the law is relatively sparse, leaving open questions as to how the FDA will implement the new requirements. In the last two years, FDA has approved the first four cell and gene therapy products, and now has more than 800 active investigational new drugs of this type under review signaling the leading edge of a wave of these new therapies. Using surrogate or intermediate clinical endpoints can save valuable time in the drug approval process. Fast Track, Breakthrough Therapy, Accelerated Approval, Priority Review, Recalls, Market Withdrawals and Safety Alerts, Fast Track, Breakthrough Therapy, Accelerated Approval, Priority Review. This promotes continued development for the given indication. Executive Summary. 7(RMavCb:@Klj~/6~zF3w?=x-{y!zq B7Cz'oAy+(s?8ABU.K^APU"N5}c)eV-*@k'%wn|rV!(L[$zz&/J6 d1L* Yd6GRzeGUr&S2[Dre(]Vb#1K}X-Bq/]L6> R: 213 0 obj <>/Filter/FlateDecode/ID[<92F9F34EFBE0F52EA7629AA646717EF5>]/Index[201 23]/Info 200 0 R/Length 71/Prev 295530/Root 202 0 R/Size 224/Type/XRef/W[1 2 1]>>stream FDA is continuously evaluating these approvals to ensure the safety and effectiveness of approved products and whether a danglingaccelerated approval indication should remain approved. Promoting the transparency of Accelerated Approval for oncology indications. Building quality and efficiency into the design of oncology clinical trials is a crucial component in providing maximum benefit to those living with cancer.. FDA Issues Guidelines to Support Applications for Accelerated Approvals These regulations allowed drugs for serious conditions that filled an unmet medical need to be approved based on a surrogate endpoint. US FDA lauds collaborative development of surrogate endpoint that allowed for accelerated approval of the first two drugs for the rare kidney disease. Qf Ml@DEHb!(`HPb0dFJ|yygs{. These reductions in tumor size need to occur in a sufficient number of patients and for a sufficient period of time (Duration of Response [DOR]). While the House and Senate proposals are similar, one difference is the Senate bills establishment of an intra-agency coordinating council within the FDA to ensure the consistent and appropriate use of accelerated approval. Among other tasks, the council would be responsible for developing guidance for FDA staff and best practices for the review of accelerated approval products. The agency seeks to improve the data available at the time of accelerated approval and reduce clinical uncertainty for patients by initiating postmarketing confirmatory studies in a timely manner.1. Since 1992, the majority ofaccelerated approvalhave been granted for oncology and hematology indications. endstream endobj 208 0 obj <>stream For rare diseases, we cant expect very large trials. These programs have key differences including the endpoints or analysis used to support approval, built-in time limits to verify benefit, and whether they apply to original products (new molecular entities) and/or new indications for previously approved products. hTOo0| The FDA may be keen to take advantage of this new provision. while maintaining access for beneficiaries. One recommendation for incentivizing drugmakers to complete their confirmatory trials quickly is to increase the monetary rebates they pay under the Medicaid program until such studies are complete. Accessed March 24, 2023. The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely. Cooleys FDA team will continue to monitor updates in this space. The FDA accelerated drug approval program: benefits and - CHEMDIV FDA'S ACCELERATED APPROVAL PATHWAY: A RARE DISEASE PERSPECTIVE History and Opportunities for Reform rarediseases.org A Report Commissioned by NORD Eva Temkin and Jonathan Trinh, King & Spalding LLP National Organization for Rare Disorders (NORD) FDA's Accelerated Approval Pathway: A Rare Disease Perspective | 2 TABLE OF CONTENTS Overall, the new legal requirements attempt to address the concerns that have emerged around the accelerated approval pathway in recent years and may help reverse some of the trends found within OIGs report. %%EOF If your condition is also rare, you may be worried that no treatment will ever be found. Sec. It was created to bring medications for serious or life-threatening conditions to market faster. A: The term danglingaccelerated approval has been used to describe approvals for which confirmatory trials did not verify clinical benefit, but for which marketing authorization continues. The agency has required post-marketing confirmatory trials to verify and describe the anticipated clinical benefit for drugs granted accelerated approval. In 2012, Congress passed the Food and Drug Administration Safety Innovations Act (FDASIA). The Center of Excellence has launched Project Confirm to promote transparency of outcomes related to accelerated approval for oncology indications. The Food and Drug Administration has developed four distinct and successful approaches to making such drugs available as rapidly as possible: Because each of these approaches implies speed, there can be confusion about the specific meaning of each and the distinctions among them. Lovisa Gustafsson, Vice President, Controlling Health Care Costs, The Commonwealth Fund, Bobby Clark and Jeff Callis, The Accelerated Approval Pathway for New Drug Therapies: Controversies and Proposed Fixes (explainer), Commonwealth Fund, July 2021. https://doi.org/10.26099/f6dq-kc46, Drug pricing reform, Prescription Drugs, Government Programs & Policies, 2023 The Commonwealth Fund. Biogen received considerable criticism to the initial price of the drug following approval, which totaled $56,000 per year for a patient of average weight. endstream endobj startxref The FDA has used its authority to revoke an accelerated cancer approval only once. Accelerated Approval Program | FDA The median time to verification of clinical benefit and granting of traditional approval is 3.1 years (range, 0.5-17.6), according to Oncology Center of Excellence staff. A: Products approved under theaccelerated approval program may be withdrawn voluntarily by the company or may be withdrawn by FDA after a public hearing. The .gov means its official.Federal government websites often end in .gov or .mil. The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely. Alzheimer's drug Leqembi, which slows disease progression, gets full The new procedure allows for additional transparency while still affording the sponsor due process. hVKk0W\[RPC! Report for accelerated and restricted approvals under Subpart H (drugs) and Subpart E (biologics) updated quarterly in January, April, July, and October, Database for status of specific requirements, Information about new and updated accelerated approvals plus recent news related to drugs, An official website of the United States government, Recalls, Market Withdrawals and Safety Alerts, Ongoing | Infectious Disease Accelerated Approvals (excluding vaccines), Verified Clinical Benefit | Infectious Disease Accelerated Approvals (excluding vaccines), Withdrawn | Infectious Disease Accelerated Approvals, Ongoing | Non-malignant Hematology, Neurological Disorders, and Other Indications Accelerated Approvals, Verified Clinical Benefit | Non-malignant Hematological, Neurological, and Other Disorder Indications Accelerated Approvals, Withdrawn | Non-malignant Hematological, Neurological, and Other Disorder Indications Accelerated Approvals, Ongoing | Infectious Disease Accelerated Approvals Vaccines, Verified Clinical Benefit | Infectious Disease Accelerated Approvals Vaccines, Drug and Biologic Approval and IND Activity Reports, Verified Clinical Benefit(excluding vaccines), Drug and Biologic Accelerated Approvals Based on a Surrogate Endpoint, Ongoing | Infectious Disease (excluding vaccines), Verified Clinical Benefit | Infectious Disease (excluding vaccines), Verified Clinical Benefit I Heme/Neuro/Other. The FDA also gave the drug a broad label, allowing it to be used on all Alzheimers patients regardless of severity, even though it had only been tested on people with early Alzheimers and mild symptoms. Mindful of the fact that it may take an extended period of time to measure a drugs intended clinical benefit, in 1992 FDA instituted the Accelerated Approval regulations. FDA's accelerated approval process: What your audience needs to know FDORA allows, but does not mandate, the FDA to require, as appropriate, that certain post-approval studies already be underway prior to accelerated approval or within a specified time from the date of approval. FDA Accelerated Approval: How Does It Affect Your Medication? March 29, 2022 In order to incentivize the development of therapies (drugs biologics) to fill unmet medical needs for treatment of serious conditions, the FDA has developed various programs to expedite drug development and review. In certain cases where there are continued unmet medical needs and there are reasons for a confirmatory trial not verifying clinical benefit an indication may remain on the market while another confirmatory trial is completed. 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These reports include accelerated and restricted approvals under Subpart H (drugs) and Subpart E (biologics) and will be updated quarterly in January, April, July, and October of each year. FDORA's Changes To The FDA Accelerated Approval Program - Mondaq In other words, patients may not want to enroll in a trial with a control or placebo arm if an effective therapy is already available on the market (the indication approved through accelerated approval). The Code of Federal Regulations will be revised to reflect the changes from FDORA. In the FDA's approval of Clolar, the. tqX)I)B>== 9. They will also potentially give payers cover to restrict coverage when a drug fails to prove its efficacy, as UnitedHealthcare did for Aduhelm. eCFR :: 21 CFR Part 314 Subpart H -- Accelerated Approval of New Drugs An official website of the United States government, : A process designed to expedite the development and review of drugs which may demonstrate substantial improvement over available therapy. In addition, the FDA must publish the withdrawal proposal for public comments and later a summary of the comments and the agencys response on its website. The FDA issued its accelerated approval regulation nearly 30 years ago, and has since applied this approach for more than 200 new drug indications. FDA. The FDA encourages sponsors interested in the accelerated approval pathway to communicate with the agency early in development to discuss proposed surrogate endpoints or intermediate clinical endpoints, plans for confirmatory trials and clinical trial design, among other topics.2. O3y6x{ MO5esc?h%~ 9 Established in 1992 in response to the HIV/AIDS crisis, the accelerated approval pathway allows the FDA to speed approval of drugs based on a surrogate endpoint rather than a direct measure of clinical benefit, as required for traditional FDA approval. B The site is secure. FDORA requires the FDA to form an intra-agency coordinating council within one year of the enactment of FDORA. Drug companies are still required to conduct studies to confirm the anticipated clinical benefit. This pathway allows for earlier approval of drugs that offer a meaningful benefit over existing therapies and treat serious conditions that have an unmet medical need. A: Drugs grantedaccelerated approval are not considered available therapy, as their clinical benefit for the specific indication has not been verified. 223 0 obj <>stream With all of these open questions, as well as the new obligations placed upon the FDA, it will likely be years before the full effects of the law are felt. [1][2] A study published in 2023, following a similar study focused on oncology in 2022, suggested that the Accelerated Approval Program was having the intended impact of shortening the timeline to either traditional approval or withdrawal of applications in cases where confirmatory trials had begun before the start of the Accelerated Approval process; further, there appeared to be no impact on the ratio of approval to withdrawal whether accelerated or traditional pathway was used. Membership includes the directors of seven specified centers and offices within the FDA, as well as at least three directors of review divisions or offices overseeing products approved under the accelerated approval pathway.8 The council is tasked with ensuring consistent and appropriate use of accelerated approval across the agency through direct engagement with product review teams. {C2R='$=M>d/{ 4W lC@g; 4BZ;i xUK The pathway has been used primarily for drugs aimed at diseases that progress slowly, such that waiting for trials that demonstrate primary clinical endpoints would result in a yearslong delay before such drugs could be eligible for approval under the traditional pathway. Approval of a drug may be withdrawn or the labeled indication of the drug changed if trials fail to verify clinical benefit or do not demonstrate sufficient clinical benefit to justify the risks associated with the drug (e.g., show a significantly smaller magnitude or duration of benefit than was anticipated based on the observed effect on the surrogate). The FDA instituted its Accelerated Approval Program to allow for earlier approval of drugs that treat serious conditions, and that fill an unmet medical need based on a surrogate endpoint. Other proposals, including those put forth by the Institute for Clinical and Economic Review, seek to address the high cost of accelerated approval drugs by tying coverage to patient benefit and the presence of an outcomes-based contract, or by creating a new safety only approval pathway that would not require public or private insurers to pay for approved treatments. The FDA's Accelerated Approval Program allows for certain drugs that treat serious conditions where there is an unmet medical need to be approved, based on the results of a "surrogate endpoint" evaluated in studies. The specified directors include the Directors of the Center for Drug Evaluation and Research and the Center for Biologics Evaluation and Research, the Director of the Oncology Center of Excellence, the Director of the Office of New Drugs, the Director of the Office of Orphan Products Development, the Director of the Office of Tissues and Advanced Therapies and the Director of the Office of Medical Policy. Our fifth expedited program (accelerated approval), which is an approval pathway rather than a designation program, enables initial approval based on surrogate endpoints with a requirement for further study post-approval. Enacted on December 29, 2022, the Consolidated Appropriations Act (the year-end omnibus spending bill) includes the Food and Drug Omnibus Reform Act (FDORA), which enhances the Food and Drug Administration's authority in several key areas. The FDA can grant accelerated approval for drugs designed to treat life-threatening diseases for which no approved treatments currently exist based upon data from surrogate endpoints (laboratory markers), so long as the endpoints are reasonably believed to predict clinical benefit. [1] Drug approval typically requires clinical trials with endpoints that demonstrate a clinical benefit, such as increased survival for cancer patients. The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely. Learn About Drug and Device Approvals, Recalls, Market Withdrawals and Safety Alerts, Fast Track, Breakthrough Therapy, Accelerated Approval, Priority Review. Over the years, the FDA has used these expedited drug development and review tools to help bring a wide range of new drugs to patients in need. FDORA creates a formal expedited withdrawal procedure for drugs approved through accelerated approval. Postapproval confirmatory trials are often delayed; in some cases, they can take more than a decade to complete. Project Confirm is an initiative of the FDA Oncology Center of Excellence to promote the transparency of outcomes related toaccelerated approval for oncology indications. [1] They also say the FDA needs clear guidelines for how and when the agency can remove a drug from the market if companies dont conduct confirmatory trials in a timely manner, or if findings from a trial indicate poor safety or effectiveness. Analysis of FDA's Accelerated Approval Program Performance - PubMed 0 Q: What are the postmarketing requirements for accelerated approval? Are these different from the endpoints used to support traditional approvals? In other words, certain post-approval studies have to start before the accelerated approval or shortly after it. Drug approvals (including accelerated approvals) are issued by FDA after review and are based on "demonstration of substantial evidence of effectiveness in treating or preventing the condition and evidence of safety for that use. Each is summarized below: Of note, we see frequently that the similar terms, expedited, fast track, and accelerated, are often confused by media sources and others, resulting in inaccuracies. Published 9:01 PM PDT, December 6, 2022 WASHINGTON (AP) Expedited drug approvals slowed this year as the Food and Drug Administration's controversial accelerated pathway came under new scrutiny from Congress, government watchdogs and some of the agency's own leaders. In early June, external advisors to the FDA unanimously recommended Leqembi for full approval. As a condition of receiving accelerated approval, sponsors are required to conduct post-approval studies to confirm the clinical benefit of the drug. Q: Do other countries have accelerated approval programs? The US Food and Drug Administration (FDA) grants accelerated approval according to surrogate measures of numerous drug indications for serious or life-threatening illnesses such as infectious diseases and cancer. These standards exist to make sure that approved drugs have a high chance of helping those who use them. The United States Food and Drug Administration (FDA) initiated the FDA Accelerated Approval Program in 1992 to allow faster approval of drugs for serious conditions that fill an unmet medical need. The expedited withdrawal procedure contained in the law also contains ambiguity as to the sequence and timing for the various reviews and appeals offered to the sponsor. The .gov means its official.Federal government websites often end in .gov or .mil. [ w{[Y9XI~nn;g{d]MQ2"]Qr E0 h]W7x4V9> hb{MsoV) Only 157 orphan drugs (those that treat rare diseases) were approved in the ten-year period, 1999 through 2008, whereas 436 have been approved in the 10-year period, 2009 through 2018. The widely expected approval comes six months to the day after the FDA gave the drug a greenlight through its accelerated pathway program. As an endpoint to support marketing authorization ORR is not limited to accelerated approval. The provisions seek to increase transparency around this regulatory pathway and also grant new authorities to the FDA to ensure that sponsors are complying with post-approval requirements that are essential to ensure that only drugs that are safe and effective for their intended use remain on the market. The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely. To accomplish this, accelerated approval are granted on the basis that products have an effect on a surrogate endpoint that is reasonably likely to predict clinical benefit, or on a clinical endpoint that can be measured earlier than irreversible morbidity or mortality, that is reasonably likely to predict an effect on irreversible morbidity or mortality or other clinical benefit, taking into account the severity, rarity, or prevalence of the condition and the availability or lack of alternative treatments (FDASIA, 21 USC 301). According to the report, Biogen knew its $56,000 launch price Speeding the availability of drugs that treat serious diseases are in everyone's interest, especially when the drugs are the first available treatment or if the drug has advantages over existing treatments. News release. FDA's accelerated approval program: Reevaluating the need - Healio The US drug regulator gave full approval to a new Alzheimer's medicine on Thursday, a move that makes it more widely available to the public through government-run health insurance for the elderly.Leqembi was initially granted "accelerated approval" by the Food and Drug Administration in January, which meant it was not broadly covered by the government-run Medicare program for people aged 65 . A few facts to illustrate the rapid evolution underway in drug discovery and development: We would argue that this change in the mix of products and diseases has resulted in many more therapies being eligible for expedited programs than in the past. Using a surrogate endpoint enabled the FDA to approve these drugs faster. A positive therapeutic effect that is clinically meaningful in the context of a given disease is known as clinical benefit. The project also aims tofoster discussion and research on the accelerated approval program. F.D.A. Rushed a Drug for Preterm Births. Did It Put Speed Over Science?