Candidate: Leronlimab (PRO 140)
Type: Humanized IgG4 monoclonal antibody. Leronlimab is CytoDyn’s lead candidate, and is a CCR5 antagonist for patients who experience respiratory illness as a result of COVID-19 with potential for multiple therapeutic indications.
Status: CytoDyn said May 19 it was providing leronlimab for a trial for severe/critical COVID-19 patients in Mexico through a collaboration with that nation’s Coordinating Commission of National Institutes of Health and High Specialty Hospitals (CCINSHAE)—with the potential to collaborate on further CytoDyn COVID-19 trials.
CytoDyn is currently enrolling patients in the up-to-390 patient, double-blinded (2:1 drug to placebo) Phase IIb/III trial (NCT04347239). The primary endpoint in that study is mortality at day 28 following treatment.
The company is also evaluating leronlimab in a 75-patient, Phase II double blinded, placebo-controlled, randomized study assessing leronlimab in mild-to-moderate COVID-19 patients (NCT04343651). The primary endpoint is clinical improvement assessed by change in total symptom score on day 14 following treatment.
CytoDyn has been granted more than 60 emergency IND authorizations by the FDA, saying it planned to provide clinical updates for this patient population later this week.
On May 5, a research team that included CytoDyn CEO Nader Z. Pourhassan, PhD, and five other investigators with ties to CytoDyn published a preprint study on Research Square and MedRxiv describing the immunological mechanism by which leronlimab restoredimmune function and impacts disease in 10 terminally-ill, critical COVID-19 patients. Leronlimab was shown to restore immunologic deficiencies, and reduce SARS-CoV-2 plasma viral load via disruption of the CCL5-CCR5 axis.
A day earlier, CytoDyn disclosed in a regulatory filing that Pourhassan sold more than 4.8 million (4,821,174) shares of CytoDyn stock between April 30 and May 4, reaping $11.96 million, after acquiring the shares by exercising stock options, then selling the resulting stock. The selloff reduced Pourhassan’s stake in the company by about half after the company had appeared on financial news shows in recent weeks to promote leronlimab, according to STAT.
Pourhassan explained the selloff as a transaction in which he borrowed $3.8 million to buy shares from CytoDyn, sold them for about $15.8 million, paid back the loan and kept the difference. He said the transaction would help the company pay for manufacturing and other expenses, without potentially denting the price of his company’s stock by raising the cash on the market.
Four days earlier, CytoDyn reported mostly positive results for 49 patients that had been treated with leronlimab. They include four of 11 severe COVID-19 patients in one New York hospital whose lives CytoDyn said were saved due to treatment with the drug; three of six severe disease patients at a Southern California hospital who were extubated; two of three Georgia patients who were also extubated; a patient at a second New York hospital who was taken off oxygen and discharged after treatment; and a Northern California patient who was weaning from a ventilator and transferred to a rehabilitation hospital.
CytoDyn said in April it would dedicate all resources to ensure availability of leronlimab for COVID-19 patients while the FDA reviewed the company’s BLA for the drug in combination with highly active antiretroviral therapy (HAART) in treatment-experienced HIV patients. The company said May 13 it submitted data required to complete its BLA application for the leronlimab-HAART combination in HIV, after stating its application was complete April 27, then disclosing it needed to submit additional data May 8 without explanation. The company has won FDA conditional acceptance of Vyrologix as the proprietary name for leronlimab.
Also, CytoDyn appointed its Chairman, Scott A. Kelly, MD, to the additional position of Chief Medical Officer and Head of Busines Development, a move it said would accelerate evaluation of leronlimab for COVID-19 and other indications.
CytoDyn has highlighted positive results from seven patients with severe COVID-19 after seven days of treatment with leronlimab: All seven showed “dramatic” immune restoration, especially in the CD8 T-lymphocyte population, and a “further dramatic” reduction in the critical cytokine storm cytokines IL-6 and TNF-alpha. At a “leading medical center in Southern California,” CytoDyn said, one severe COVID-19 patient was removed from external ventilation three days after treatment with leronlimab, and two moderate COVID-19 patients were removed from external oxygen support one day following leronlimab treatment, and discharged from the hospital. Based on these results, another four patients with moderate COVID-19 have been administered leronlimab and results are pending, CytoDyn said.
In the U.K., CytoDyn is collaborating with the U.K.’s Department of Health to provide emergency access to leronlimab for severe and critically ill COVID-19 patients, with a formal request to be submitted soon to the Medicines and Healthcare Products Regulatory Agency (MHRA).
CytoDyn said April 2 eight severely ill COVID-19 patients treated with leronlimab showed “significant improvement” in immunologic biomarkers: “We continue to see increases in the profoundly decreased CD8 T-lymphocyte percentages by Day 3, normalization of CD4/CD8 ratios, and resolving cytokine production including reduced IL-6 correlating with patient improvement,” stated Bruce Patterson, MD, CEO and founder of IncellDx, a diagnostic partner and advisor to CytoDyn.
CytoDyn and Longen China Group has said they will begin exploring leronlimab as a potential treatment for coronavirus as well as cancer.
Leronlimab has completed nine clinical trials in over 800 people, according to CytoDyn, including meeting its primary endpoints in a pivotal Phase III trial in combination with standard antiretroviral therapies in HIV-infected treatment-experienced patients. CytoDyn plans to file a BLA with the FDA in HIV during Q1 2020. Leronlimab has the FDA’s Fast Track designation as a combination therapy with highly active antiretroviral therapy (HAART) for HIV-infected patients, and for metastatic triple-negative breast cancer—for which CytoDyn saiod April 3 it has requested to meet with the FDA to discuss new clinical data in support of a Breakthrough Therapy designation from the agency.
COVID-19: 200 Candidates and Counting
To navigate through the >200 potential therapeutic and vaccine options for COVID-19, GEN has grouped the candidates into four broad categories based on their developmental and (where applicable) clinical progress:
● FRONT RUNNER – the most promising therapeutics/vaccines based on clinical progress, favorable data or both.
● DEFINITELY MAYBE – earlier phases with promising partners, or more advanced candidates in development that have generated uneven data
● KEEPING AN EYE ON… – interesting technology, attracting notable partners, or both, but preliminary data.
● TOO SOON TO TELL – longshots pending additional experimental and/or clinical data.
GEN has also tagged the most common treatment types: