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WARNING LETTER

CytoDyn, Inc. MARCS-CMS 626957 —

Product:
Drugs
Recipient:
Recipient Name
Antonio Migliarese
Recipient Title
Interim President and Chief Financial Officer
CytoDyn, Inc.

1111 Main Street, Suite 660
Vancouver, WA 98660
United States

Issuing Office:
The Office of Prescription Drug Promotion (OPDP)

United States

RE: (b)(4)
leronlimab
MA 3

WARNING LETTER

Dear Mr. Migliarese:

The Office of Prescription Drug Promotion (OPDP) of the U.S. Food and Drug Administration (FDA) has reviewed a video interview (video)1 with Proactive Media dated September 22, 2021, featuring Dr. Nader Pourhassan,2 and made available via hyperlink on the corporate website for CytoDyn, Inc. (CytoDyn). In the video, Dr. Pourhassan discusses the investigational new drug leronlimab, which is the subject of the above-referenced investigational new drug application (IND). The video represents in a promotional context that leronlimab, an investigational new drug, is safe and effective for the purpose for which it is being investigated or otherwise promotes the drug. As a result, leronlimab is misbranded under section 502(f)(1) of the Federal Food, Drug, and Cosmetic Act (FD&C Act) and is in violation of section 301(a) of the FD&C Act. The video is concerning from a public health perspective because it suggests that leronlimab provides a clinical benefit to individuals with “Coronavirus Disease 2019” (COVID-19), which, in its most severe form, can result in respiratory failure and death. The video makes conclusory representations in a promotional context regarding the safety and efficacy of leronlimab, an investigational drug, that has not been approved or authorized by the FDA and whose safety and efficacy has not yet been established.

There is currently a global outbreak of respiratory disease caused by a novel coronavirus that has been named “severe acute respiratory syndrome coronavirus 2” (SARS-CoV-2). The disease caused by the virus has been named COVID-19. On January 31, 2020, the Department of Health and Human Services (HHS) issued a declaration of a public health emergency related to COVID-19 and mobilized the Operating Divisions of HHS.3 In addition, on March 13, 2020, there was a Presidential declaration of a national emergency in response to COVID-19.4 Therefore, FDA is taking measures to protect consumers from certain products that, without approval, clearance, or authorization by FDA, claim to mitigate, prevent, treat, diagnose, or cure COVID-19 in people.

Background

Leronlimab is an investigational new drug for which there is no emergency use authorization or marketing approval in the United States. An IND for leronlimab was submitted to the FDA on (b)(4). Per the IND application, leronlimab is being investigated for the treatment of COVID-19.

Prior Communications

On May 17, 2021, following public communications by CytoDyn regarding differences in small subgroups in one of the clinical trials CytoDyn conducted with leronlimab for the treatment of patients with COVID-19, including those with severe outcomes from COVID-19, FDA issued a statement5 addressing CytoDyn’s development of leronlimab. The statement reviewed the results of two clinical trials, CD10 and CD12, conducted by CytoDyn investigating leronlimab for the treatment of COVID-19. In part, the statement provided, “With the conclusion of both the CD10 and CD12 clinical trials, it has become clear that the data currently available do not support the clinical benefit of leronlimab for the treatment of COVID-19.”

(b)(4)

Misbranding of an Investigational Drug

Under section 502(f)(1) of the FD&C Act, a drug shall be deemed to be misbranded unless its labeling bears adequate directions for use. Under FDA regulations, adequate directions for use means directions under which the layman can use a drug safely and for the purposes for which it is intended. 21 CFR 201.5. The video describes the use of leronlimab for the treatment of COVID-19. This use is one for which a prescription would be needed because it requires the supervision of a physician and, therefore, for which adequate directions for lay use cannot be written.

Although 21 CFR 201.115(b) provides an exemption from the adequate directions for use requirement in section 502(f)(1) of the FD&C Act if a new drug “complies with section 505(i)…and regulations thereunder,” your investigational drug fails to do so6. Among the requirements for this exemption for investigational drugs, 21 CFR 312.7(a) provides that, “[a] sponsor or investigator, or any person acting on behalf of a sponsor or investigator, shall not represent in a promotional context that an investigational new drug is safe or effective for the purposes for which it is under investigation or otherwise promote the drug. This provision is not intended to restrict the full exchange of scientific information concerning the drug, including dissemination of scientific findings in scientific or lay media. Rather, its intent is to restrict promotional claims of safety or effectiveness of the drug for a use for which it is under investigation and to preclude commercialization of the drug before it is approved for commercial distribution.”

The video includes claims that promote leronlimab as safe and effective for the purposes for which it is being investigated or otherwise promote the drug, including the following examples (underlined emphasis added):

  • “In the United States, we did a trial of 394 patients which included severe and criticallyill population. In the critically-ill population, our results were really strong. . .”
  • “Our critically-ill population that we did in the United States when we gave a dose of leronlimab, the survival rate was 78%. Once we gave them another dose, the survival rate went up to 82%.”
  • “Imagine, if 78% went to 82, the next one would be maybe 88, and then 95. I am making up numbers, but if it goes to that kind of numbers, if it just follows the same pattern what we learned, this is going to be the most fantastic results anybody could ever imagined to have. Now I’m not saying that’s what we’re going to get, but I’m saying that’s what the results are showing.”
  • “The primary endpoint…is the discharge, the rate of patients who get on ventilator and get discharged. That endpoint was 166% better in our trial that we did in the United States versus placebo…166%.”

The above claims make numerous conclusory statements that suggest that leronlimab has been established as safe and effective for the treatment of COVID-19. However, leronlimab is an investigational new drug, for which the product’s indication(s), warnings, precautions, adverse reactions, and dosage and administration have not been established. Furthermore, the video is extremely concerning because it significantly mischaracterizes the clinical trial data for leronlimab in the treatment of COVID-19, and the stated conclusions based on this mischaracterized data create a misleading impression regarding the safety and efficacy of the product. As was noted in FDA’s May 17, 2021 statement, the larger trial that CytoDyn conducted in patients with severe COVID-19 disease (CD12) failed to find any effect of the drug on the primary study endpoint of Day 28 all-cause mortality (20.5% in the leronlimab treatment group and 21.6% in the placebo treatment group) or any predefined secondary endpoints. In addition, as was also noted in FDA’s statement, with the conclusion of the CD12 trial, it has become clear that the data currently available do not support the clinical benefit of leronlimab for the treatment of COVID-19. The suggestion that leronlimab has established “really strong” results in the treatment and the “survival” of critically ill COVID-19 patients is especially troubling given the public health emergency related to COVID-19, the limited available treatment options, and the fact that COVID-19 is a disease that, in its most severe form, can lead to hospitalization, respiratory failure, and death.

In summary, the video represents the drug as having an established role in the treatment of COVID-19, when leronlimab has not been proven as safe or effective within the meaning of the FD&C Act and has not been approved as a drug, nor granted an emergency use authorization under that authority for any use.

Conclusion and Requested Action

For the reasons discussed above, the video misbrands leronlimab under section 502(f)(1) of the FD&C Act and in violation of section 301(a) of the FD&C Act. The claims in the video are concerning because they make representations in a promotional context regarding the safety and efficacy of an investigational new drug that has not been approved or authorized by the FDA.

This letter notifies you of our concerns and provides you with an opportunity to address them. OPDP requests that CytoDyn cease any violations of the FD&C Act. Please submit a written response to this letter within 15 working days from the date of receipt, addressing the concerns described in this letter, listing all other promotional communications for leronlimab that contain representations such as those described above, and explaining any plan for discontinuing use of such communications, or for ceasing distribution of leronlimab.

Failure to adequately address this matter may lead to regulatory action. If you believe that your products are not in violation of the FD&C Act, please include in your submission to us your reasoning and any supporting information for our consideration within 15 working days from the date of receipt of this letter.

Additionally, we request that your submission include a comprehensive plan of action to disseminate truthful, non-misleading, and complete corrective communication(s) about the concern(s) discussed in this letter. The corrective communication(s) should be disseminated to the audience(s) that received the promotional communication(s) identified in the opening paragraph of this letter. OPDP recommends that corrective communication(s) include a description of the promotional communication(s) identified in this letter, which misbrand leronlimab; include a summary of the concern(s) described in this letter; and provide information to correct each of these concern(s). Corrective communication(s) should be free of promotional claims and presentations. To the extent possible, corrective communication(s) should be distributed using the same media, and generally for the same duration of time and with the same frequency as the promotional communication(s) identified in the opening paragraph of this letter.

The concerns discussed in this letter do not necessarily constitute an exhaustive list of potential violations. It is your responsibility to ensure compliance with each applicable requirement of the FD&C Act and FDA implementing regulations.

Please direct your response to the undersigned at the Food and Drug Administration, Center for Drug Evaluation and Research, Office of Prescription Drug Promotion, 5901-B Ammendale Road, Beltsville, Maryland 20705-1266. A courtesy copy can be sent by facsimile to (301) 847-8444. Please refer to MA 3 in addition to the IND number in all future correspondence relating to this particular matter. All correspondence should include a subject line that clearly identifies the submission as a Response to Warning Letter. You are encouraged, but not required, to submit your response in eCTD format. All correspondence submitted in response to this letter should be placed under eCTD Heading 1.15.1.6. Questions related to the submission of your response letter should be emailed to the OPDP RPM at CDER-OPDP-RPM@fda.hhs.gov.

Sincerely,
{See appended electronic signature page}
Andrew S.T. Haffer, Pharm.D.
Director
Division of Advertising & Promotion Review 1
Office of Prescription Drug Promotion

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This is a representation of an electronic record that was signed electronically. Following this are manifestations of any and all electronic signatures for this electronic record.
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/s/
------------------------------------------------------------
KATHLEEN KLEMM
02/11/2022 10:26:47 AM
Signed on behalf of Andrew S. Haffer
______________________

1 A link to the video is available on the internet at cytodyn.com as a hyperlink titled “Brazil has approved critically ill COVID Phase 3 to begin.” The hyperlink directs to the video on the Proactive Media YouTube page at https://www.youtube.com/watch?v=IeUGEMtcmPs (last accessed on February 11, 2022). According to the Proactive Media YouTube page at https://www.youtube.com/c/Proactive247/about, “Proactive is a publisher and receives compensation for publishing content on this account for and on behalf of its clients.”

2 We note that until January 24, 2022, Dr. Pourhassan was the President and Chief Executive Officer of CytoDyn, Inc.

3 Secretary of Health and Human Services, Determination that a Public Health Emergency Exists (originally issued Jan. 31, 2020, and subsequently renewed), available at https://www.phe.gov/emergency/news/healthactions/phe/Pages/default.aspx.

4 Proclamation on Declaring a National Emergency Concerning the Novel Coronavirus Disease (COVID-19) Outbreak (Mar. 13, 2020), available at https://trumpwhitehouse.archives.gov/presidential-actions/proclamationdeclaring-national-emergency-concerning-novel-coronavirus-disease-covid-19-outbreak/.

5 FDA “Statement on Leronlimab,” available at https://www.fda.gov/drugs/drug-safety-and-availability/statementleronlimab (last accessed on February 11, 2022).

6 21 CFR 201.100 offers another exemption from the requirement for adequate directions for use for prescription drugs provided certain requirements are met; however, leronlimab does not fall within that exemption because there is no marketing approval in the United States.

 
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