FDA Approves New Treatment for Alzheimer’s Disease

In an interesting decision FDA decided on June 7 to approve a controversial new treatment for Alzheimer’s Disease, Aducanumab (trade name Aduhelm)

What is Aduhelm?

Aduhelm is an amyloid beta-directed antibody indicated for the treatment of Alzheimer’s disease.

Why FDA Decided to Approve Aduhelm to Treat Alzheimer’s Disease https://www.fda.gov/drugs/news-events-human-drugs/fdas-decision-approve-new-treatment-alzheimers-disease

Approval Path: Aduhelm was approved under the Accelerated Pathway. According to Dr. Patrizia Cavazzoni, Director, FDA Center for Drug Evaluation and ResearchCDER Director the “Accelerated Approval https://www.fda.gov/drugs/information-health-care-professionals-drugs/accelerated-approval-program pathway, under which the FDA approves a drug for a serious or life-threatening illness that may provide meaningful therapeutic benefit over existing treatments when the drug is shown to have an effect on a surrogate endpoint that is reasonably likely to predict a clinical benefit to patients and there remains some uncertainty about the drug’s clinical benefit.” Further, FDA consider Aduhelm a novel treatment. The last time a treatment for Alzheimer’s was approved was in 2003. Dr. Cavazzoni emphasized that “Aduhelm is the first treatment directed at the underlying pathophysiology of Alzheimer’s disease, the presence of amyloid beta plaques in the brain.”

Dr. Cavazzoni concluded that : “FDA will continue to monitor Aduhelm as it reaches the market and ultimately the patient’s bedside. Additionally, FDA is requiring Biogen to conduct a post-approval clinical trial to verify the drug’s clinical benefit. If the drug does not work as intended, we can take steps to remove it from the market. But hopefully, we will see further evidence of benefit in the clinical trial and as greater numbers of people receive Aduhelm.” https://www.fda.gov/drugs/news-events-human-drugs/fdas-decision-approve-new-treatment-alzheimers-disease

Emergency Use Authorization vs. Approval and Other Key Terminology

Following Pfizer BioNTech’s Biologics License application, Moderna filed a Biologics License application. Currently Pfizer BioNTech and Moderna were granted Emergency Use Authorization Status.

Understanding the Regulatory Terminology of Potential Preventions and Treatments for COVID-19

See links or read below.

https://www.fda.gov/consumers/consumer-updates/understanding-regulatory-terminology-potential-preventions-and-treatments-covid-19

https://www.fda.gov/media/138490/download

“There’s a lot of confusion about which medical products might work to prevent or treat coronavirus disease 2019 (COVID-19). Scientists are working hard to develop a number of potential drugs for the prevention or treatment of coronavirus.The FDA recently approved the first treatment for COVID-19, the antiviral drug remdesivir. Some other investigational drugs are already in clinical trials. In some cases, scientists are testing whether drugs that are already approved for a different disease are safe and effective against COVID-19.As studies continue, these drugs are sometimes made available to patients through the FDA’s Expanded Access Program, or under an Emergency Use Authorization. Health care providers may also decide to treat a patient with a drug that has been approved by the FDA for one use, but not for the patient’s disease or condition (sometimes called “off-label” use).If you think you have, or have had, COVID-19, your health care provider has a complete picture of your health and health history and can help you make the best decisions for your care.The language used to describe potential therapies can be confusing, and there’s public interest around the FDA’s work to ensure access to potentially life-saving treatments. Here’s what those terms mean.

What “FDA Approved” Means

U.S. consumers rely on the FDA to provide independent scientific reviews of medical products, including drugs and vaccines. During this public health emergency, there is an urgent need for products to treat or prevent the virus that causes COVID-19. Before the FDA can approve a drug, the agency must determine whether the clinical data and other information show that the drug is safe and effective for its intended use (for example, to prevent or treat a certain disease), and that the product can be made according to federal quality standards.When the FDA approves a drug, it means the agency has determined, based on substantial evidence, that the drug is effective for its intended use, and that the benefits of the drug outweigh its risks when used according to the product’s approved labeling.The FDA is working with manufacturers and researchers to make sure the agency is getting the information needed to complete that evaluation for drugs to treat or prevent COVID-19 as quickly as possible.

Investigational Treatments

An investigational drug can also be called an experimental drug. Scientists conduct clinical trials to study investigational drugs to see if they can safely and effectively prevent or treat a specific disease or condition. As part of those clinical trials, they might try to discover:

  • How the drug might be used for that disease or condition.
  • If the drug is safe for people.
  • How much of the drug is needed. 
  • Information about whether it works against the disease and the potential benefits and risks of taking the drug.

Expanded Access

Sometimes called “compassionate use,” expanded access is a potential pathway for a patient with a serious or immediately life-threatening disease or condition to gain access to an investigational medical product (drug, biological product, or medical device) for treatment outside of clinical trials when there is no comparable or satisfactory alternative therapy.

Currently, expanded access is one pathway for use of COVID-19 convalescent plasma for patients with serious or immediately life-threatening COVID-19 disease who are not eligible for or who are unable to participate in randomized clinical trials.

Limited information suggests that convalescent plasma – an antibody-rich product made from blood donated by people who have recovered from the virus – may help COVID-19 patients. Because current information is limited, it’s important to evaluate this therapy in the context of a clinical trial.

Emergency Use Authorization (EUA)

An Emergency Use Authorization (EUA) is one of several tools the FDA is using to help make certain medical products available quickly during the COVID-19 pandemic. In certain emergencies, the FDA can issue an EUA to provide access to medical products that may potentially be used when there are no adequate, approved, and available options.

The EUA process is different than an FDA approval or clearance. Under an EUA, in an emergency, the FDA makes a product available to the public based on the best available evidence, without waiting for all the evidence that would be needed for FDA approval or clearance.

When evaluating an EUA, we carefully balance the potential risks and benefits of the products based on the data currently available. 

EUAs are effective until the emergency declaration ends. EUAs can also be revised or revoked by the FDA at any time as we continue to evaluate the available data and patient needs during the public health emergency.

The FDA has granted EUAs to a few possible COVID-19 therapies. Learn more about EUAs in this videoExternal Link Disclaimer.

“Off-Label” Use: Unapproved Uses of Approved Drugs

Once the FDA has approved a drug for a disease or medical condition, health care providers generally may prescribe or administer the drug in clinical practice for an unapproved use not described in the approved labeling (i.e., “off-label”) based on their medical judgment, recognizing that the FDA has not assessed the safety or effectiveness of such use.”

FDA Authorizes Emergency Use for Adolescents – Pfizer-BioNTech COVID-19 Vaccine

https://www.fda.gov/news-events/press-announcements/coronavirus-covid-19-update-fda-authorizes-pfizer-biontech-covid-19-vaccine-emergency-use

On May 10, another milestone occurred in the quest to prevent coronavirus disease commonly known as COVID-19. FDA gave the go ahead for expanded emergency use authorization (EUA) to Pfizer-BioNTech for the adolescent age group from ages 12 though 15.

According to FDA, approximately 1.5million cases of COVID-19 have occurred in that age group from March 1, 2020 through April 30, 2021.

Acting FDA Commissioner Janet Woodcock, M.D. “Today’s action allows for a younger population to be protected from COVID-19, bringing us closer to returning to a sense of normalcy and to ending the pandemic. Parents and guardians can rest assured that the agency undertook a rigorous and thorough review of all available data, as we have with all of our COVID-19 vaccine emergency use authorizations.”

Further, on May 10, FDA recently updated the Fact Sheets for Vaccine Providers, Recipients and Caregivers- direct links:

Healthcare Providers: https://www.fda.gov/media/144413/download

Recipients and Caregivers: https://www.fda.gov/media/144414/download

CDC Panel Recommends J&J Restart of COVID-19 Vaccine

https://www.cdc.gov/vaccines/acip/index.html

The committee voted 10 to 4 to recommend use of the vaccine, with one abstention.

Meeting convened on April 23 and link above contains presentation slides.

NOTE: CDC Panel Members proposed that the FDA include a warning label that in rare cases the vaccine has caused clotting in women under 50.

FDA Emergency Use Authorization

https://www.fda.gov/news-events/press-announcements/fda-issues-emergency-use-authorization-third-covid-19-vaccine

FDA Press Release

For Immediate Release:February 27, 2021

On Feb. 27 the U.S. Food and Drug Administration issued an #emergency use authorization (EUA) for the third vaccine for the prevention of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The EUA allows the Janssen COVID-19 Vaccine to be distributed in the U.S for use in individuals 18 years of age and older.

“The authorization of this vaccine expands the availability of vaccines, the best medical prevention method for COVID-19, to help us in the fight against this pandemic, which has claimed over half a million lives in the United States,” said Acting FDA Commissioner Janet Woodcock, M.D. “The FDA, through our open and transparent scientific review process, has now authorized three COVID-19 vaccines with the urgency called for during this pandemic, using the agency’s rigorous standards for safety, effectiveness and manufacturing quality needed to support emergency use authorization.”

The FDA has determined that the Janssen COVID-19 Vaccine has met the statutory criteria for issuance of an EUA. The totality of the available data provides clear evidence that the Janssen COVID-19 Vaccine may be effective in preventing COVID-19. The data also show that the vaccine’s known and potential benefits outweigh its known and potential risks, supporting the company’s request for the vaccine’s use in people 18 years of age and older. In making this determination, the FDA can assure the public and medical community that it has conducted a thorough evaluation of the available safety, effectiveness and manufacturing quality information.

The Janssen COVID-19 Vaccine is manufactured using a specific type of virus called adenovirus type 26 (Ad26). The vaccine uses Ad26 to deliver a piece of the DNA, or genetic material, that is used to make the distinctive “spike” protein of the SARS-CoV-2 virus. While adenoviruses are a group of viruses that are relatively common, Ad26, which can cause cold symptoms and pink eye, has been modified for the vaccine so that it cannot replicate in the human body to cause illness. After a person receives this vaccine, the body can temporarily make the spike protein, which does not cause disease, but triggers the immune system to learn to react defensively, producing an immune response against SARS-CoV-2.

“After a thorough analysis of the data, the FDA’s scientists and physicians have determined that the vaccine meets the FDA’s expectations for safety and effectiveness appropriate for the authorization of a vaccine for emergency use,” said Peter Marks, M.D., Ph.D., director of the FDA’s Center for Biologics Evaluation and Research. “With today’s authorization, we are adding another vaccine in our medical toolbox to fight this virus. At the same time, the American people can be assured of the FDA’s unwavering commitment to public health through our comprehensive and rigorous evaluation of the data submitted for vaccines to prevent COVID-19.”

FDA Evaluation of Available Safety Data

The Janssen COVID-19 Vaccine is administered as a single dose. The available safety data to support the EUA include an analysis of 43,783 participants enrolled in an ongoing randomized, placebo-controlled study being conducted in South Africa, certain countries in South America, Mexico, and the U.S. The participants, 21,895 of whom received the vaccine and 21,888 of whom received saline placebo, were followed for a median of eight weeks after vaccination. The most commonly reported side effects were pain at the injection site, headache, fatigue, muscle aches and nausea. Most of these side effects were mild to moderate in severity and lasted 1-2 days.

As part of the authorization, the FDA notes that it is mandatory for Janssen Biotech Inc. and vaccination providers to report the following to the Vaccine Adverse Event Reporting System (VAERS) for Janssen COVID-19 Vaccine: serious adverse events, cases of Multisystem Inflammatory Syndrome and cases of COVID-19 that result in hospitalization or death. 

It is also mandatory for vaccination providers to report all vaccine administration errors to VAERS for which they become aware and for Janssen Biotech Inc. to include a summary and analysis of all identified vaccine administration errors in monthly safety reports submitted to the FDA.

#COVID-19 Update: #FDA Advisory Committee Meeting for Possible #Emergency Authorization #Janssen Biotech Inc.’s COVID-19 Vaccine

FDA Vaccines and Related Biological Products Advisory Committee (VRBPAC)to consider request by Janssen Biotech Inc.’s division of J&J. According to Acting FDA Commissioner Janet Woodcock, M.D.

 “A public discussion by the advisory committee members about the data submitted in support of safety and effectiveness of Janssen Biotech Inc.’s COVID-19 vaccine will help ensure that the public has a clear understanding of the scientific data and information that FDA will evaluate in order to make a decision about whether to authorize this vaccine,” “The FDA remains committed to keeping the public informed about our evaluation of the data for COVID-19 vaccines, so that the American public and medical community have trust and confidence in FDA-authorized vaccines. 

https://www.fda.gov/news-events/press-announcements/coronavirus-covid-19-update-fda-announces-advisory-committee-meeting-discuss-janssen-biotech-incs

FEB. 26 VRBPAC meeting will be livestreamed on YouTube, Facebook and Twitter channels and webcast the FDA website

Stayed tuned for Federal Register Notice for comment submission.

FDA COVID-19 Treatment Approval

First FDA Approval for COVID-19: Veklury (remdesivir), an antiviral drug, manufactured by Gilead. It is for use in adult and pediatric patients 12 years of age and older and weighing at least 40 kilograms (about 88 pounds) for the treatment of COVID-19 requiring hospitalization. 

The FDA granted Gilead’s application Fast Track and Priority Review designations. Further FDA granted this application a  Material Threat Medical Countermeasure Priority Review Voucher. This means additional incentives because COVID-19 falls within this category; that is, medical products intended to treat or prevent harm from specific chemical, biological, radiological and nuclear threats. It is important to mention that this approval does not include the entire population that had been authorized to use Veklury under an Emergency Use Authorization (EUA) (issued on May 1, 2020). 

NOTE—FDA had granted Gilead Sciences Orphan Drug status for remdesivir and orphan designation for the “Treatment of coronavirus disease 2019 (COVID-19)” (March 23, 2020) which means tax advantages and exclusivity; however, in an unusual twist,  Gilead requested on March 25, 2020 that FDA rescind orphan drug designation.

https://www.fda.gov/news-events/press-announcements/fda-approves-first-treatment-covid-19

https://www.gilead.com/news-and-press/press-room/press-releases/2020/10/us-food-and-drug-administration-approves-gileads-antiviral-veklury-remdesivir-for-treatment-of-covid19

Practice of Medicine or Drug Biologic Product—Regenerative Sciences, LLC

“Practice of Medicine” or FDA Authority to Regulate

The Food and Drug Administration and the Authority to Regulate

USA v Regenerative Sciences

Regenerative Sciences, LLC vigorously defended its position that FDA could not regulate the practice of medicine in its Regenexx™ treatment or Regenexx-C™ cultured treatment which uses Mesenchymal adult stem cells (MSCs) that originate primarily from bone marrow. The company promotes the Regenexx™ treatment as a “non-surgical” treatment option for joint or bone pain in the hip, knee, shoulder, back or ankle as well as non-union fractures. The dispute with FDA has been ongoing since at least 2008 when FDA sent correspondence to Regenerative Sciences depicting the cell treatment as a drug or biologic. FDA conducted an inspection and found violations of current Good Manufacturing Practices (cGMPs). The United States Court of Appeals for the District of Columbia Circuit upheld the District Court and the United States Food and Drug Administration’s (FDA’s) argument that Regenerative Sciences “Cultured Regenexx Procedure” was a biological drug subject to FDA approval through the biologics licensing application (BLA) process. The court of appeals upheld the permanent injunction against the use of the biological drug without FDA approval. The issue focused on the practice of medicine versus the regulation by the United States Food and Drug Administration. This distinction has far reaching ramifications. 

Issue the Court of Appeals Addressed

In the civil enforcement action, the court of appeals had to decide “whether the appellants—three individuals and a related corporate entity—violated federal laws regulating the manufacture and labeling of drugs and biological products by producing, as part of their medical practice, a substance consisting of a mixture of a patient’s stem cells and the antibiotic doxycycline.” The court of appeals determined that FDA had the authority to regulate the product and affirmed the district court’s judgment and the permanent injunction it entered against appellants.

What Regenerative Sciences, LLC Argued

Regenerative Sciences, LLC (Regenerative Sciences) alleged several arguments that their product did not fall within FDA regulatory authority; however, the court rejected all of the arguments. For example, Regenerative argued that the Federal Food, Drug, and Cosmetic Act (FDCA) did not apply because the product was a procedure overseen by state “practice of medicine”. Another argument advanced by Regenerative Sciences was that the product was exempt from FDA approval because it was a compounded product and further it was a minimally manipulated product. As mentioned, the court of appeals rejected all of the arguments advanced by Regenerative Sciences.

Looking Ahead

This was a long awaited decision. The future is uncertain in terms of how a court will rule about novel therapies such as the issue in this case. However, no doubt as more technological advances occur, FDA will again be challenged as to the agency’s authority to regulate such products and or procedures.The link to the full case is as follows:

USA v Regenerative Sciences