June 01, 2020: “CytoDyn announced that it has filed with the U.S. FDA a request seeking Priority Review designation for the Company’s Biologics License Application (BLA) for leronlimab as a combination therapy for HIV indication.
Under the Prescription Drug User Fee Act (PDUFA), FDA agreed to specific goals for improving the drug review time and created a two-tiered system of review times – Standard Review and Priority Review.
A Priority Review designation means FDA’s goal is to take action on an application within 6 months (compared to 10 months under standard review).
FDA informs the applicant of a Priority Review designation within 60 days.
A Priority Reviewdesignation will direct overall attention and resources to the evaluation of applications for drugs that, if approved, would be significant improvements in the safety or effectiveness of the treatment, diagnosis, or prevention of serious conditions when compared to standard applications.
Significant improvement may be demonstrated by the following examples:
- evidence of increased effectiveness in treatment, prevention, or diagnosis of condition;
- elimination or substantial reduction of a treatment-limiting drug reaction;
- documented enhancement of patient compliance that is expected to lead to an improvement in serious outcomes; or
- evidence of safety and effectiveness in a new subpopulation.
Nader Pourhassan, Ph.D., President and Chief Executive Officer of CytoDyn, commented, “We look forward to the FDA’s decision on our important request and are hopeful that we can bring leronlimab therapy to highly treatment experienced HIV patients by late 2020. Leronlimab’s potential for many other indications could be expedited, should the Company receive its first approval. All other potential indications (and we believe there are many) could have a much faster approval process as label expansion approvals.”
Coronavirus Disease 2019
CytoDyn is currently enrolling patients in two clinical trials for COVID-19, a Phase 2 randomized clinical trial for mild-to-moderate COVID-19 population in the U.S. and a Phase 2b/3 randomized clinical trial for severe and critically ill COVID-19 population in several hospitals throughout the country.
SARS-CoV-2 was identified as the cause of an outbreak of respiratory illness first detected in Wuhan, China.
The origin of SARS-CoV-2 causing the COVID-19 disease is uncertain, and the virus is highly contagious. COVID-19 typically transmits person to person through respiratory droplets, commonly resulting from coughing, sneezing, and close personal contact.
Coronaviruses are a large family of viruses, some causing illness in people and others that circulate among animals.
For confirmed COVID-19 infections, symptoms have included fever, cough, and shortness of breath. The symptoms of COVID-19 may appear in as few as two days or as long as 14 days after exposure.
Clinical manifestations in patients have ranged from non-existent to severe and fatal. At this time, there are minimal treatment options for COVID-19.
Leronlimab (PRO 140) and BLA Submission for the HIV Combination Therapy
The FDA has granted a “Fast Track” designation to CytoDyn for two potential indications of leronlimab for deadly diseases. The first as a combination therapy with HAART for HIV-infected patients and the second is for metastatic triple-negative breast cancer.
Leronlimab is an investigational humanized IgG4 mAb that blocks CCR5, a cellular receptor that is important in HIV infection, tumor metastases, and other diseases, including NASH.
Leronlimab has completed nine clinical trials in over 800 people, including meeting its primary endpoints in a pivotal Phase 3 trial (leronlimab in combination with standard antiretroviral therapies in HIV-infected treatment-experienced patients).
In the setting of HIV/AIDS, leronlimab is a viral-entry inhibitor; it masks CCR5, thus protecting healthy T cells from viral infection by blocking the predominant HIV (R5) subtype from entering those cells.
Leronlimab has been the subject of nine clinical trials, each of which demonstrated that leronlimab could significantly reduce or control HIV viral load in humans.
The leronlimab antibody appears to be a powerful antiviral agent leading to potentially fewer side effects and less frequent dosing requirements compared with daily drug therapies currently in use.
The Company filed its BLA for Leronlimab as a Combination Therapy for Highly Treatment Experienced HIV Patients with the FDA on April 27, 2020, and submitted additional FDA requested clinical datasets on May 11, 2020.
After the BLA submission is deemed completed, the FDA sets a PDUFA goal date. CytoDyn has Fast Track designation for leronlimab and a rolling review for its BLA, as previously assigned by the FDA, and the Company filed a request for Priority Review designation for the BLA with the FDA.
A Priority Review designation means the FDA’s goal is to take action on the marketing application within six months (compared with 10 months under standard review).
In the setting of cancer, research has shown that CCR5 may play a role in tumor invasion, metastases, and tumor microenvironment control. Increased CCR5 expression is an indicator of disease status in several cancers.
Published studies have shown that blocking CCR5 can reduce tumor metastases in laboratory and animal models of aggressive breast and prostate cancer. Leronlimab reduced human breast cancer metastasis by more than 98% in a murine xenograft model.
CytoDyn is, therefore, conducting a Phase 1b/2 human clinical trial in metastatic triple-negative breast cancer and was granted Fast Track designation in May 2019.
The CCR5 receptor appears to play a central role in modulating immune cell trafficking to sites of inflammation. It may be crucial in the development of acute graft-versus-host disease (GvHD) and other inflammatory conditions.
Clinical studies by others further support the concept that blocking CCR5 using a chemical inhibitor can reduce the clinical impact of acute GvHD without significantly affecting the engraftment of transplanted bone marrow stem cells.
CytoDyn is currently conducting a Phase 2 clinical study with leronlimab to support further the concept that the CCR5 receptor on engrafted cells is critical for the development of acute GvHD, blocking the CCR5 receptor from recognizing specific immune signaling molecules is a viable approach to mitigating acute GvHD.
The FDA has granted “orphan drug” designation to leronlimab for the prevention of GvHD.”
