CytoDyn Files for FDA Breakthrough Therapy Status for Leronlimab for Metastatic TNBC

CytoDyn Files for FDA Breakthrough Therapy Status for Leronlimab for Metastatic TNBC

CytoDyn has requested breakthrough therapy designation from the U.S. Food and Drug Administration (FDA) for its investigational therapy leronlimab (PRO 140) as an adjuvant treatment for metastatic triple-negative breast cancer (TNBC).

Breakthrough therapy designation is given to medications that have the potential to provide significant advantages over currently available options. It is intended to accelerate the development, review, and approval of treatments for serious or life-threatening conditions. The FDA has already granted the therapy fast track designation for the same indication.

Leronlimab is an investigational antibody that blocks CCR5, a protein whose levels are increased in several cancers, including triple-negative breast cancer.

Preclinical studies have shown that by blocking CCR5, leronlimab decreased tumor cell migration in the laboratory and in animal models of aggressive breast and prostate cancer — reducing metastasis by more than 98% in a mouse model of breast cancer. It also made cells more sensitive to chemotherapeutic agents.

The submission for breakthrough therapy status was based on results from the first patient enrolled in CytoDyn’s Phase 1b/2 clinical trial (NCT03838367), which showed that treatment with leronlimab, in combination with the chemotherapy agent carboplatin, led to no detectable circulating tumor cells or metastatic tumor cells in the blood.

The patient also exhibited a significant decrease in CCR5 expression on cancer-associated cells at 11 weeks of leronlimab treatment, and tumor shrinkage of more than 20% after a few weeks of treatment.

“In the early stages of these clinical trials, we are seeing remarkable improvements in patients living with metastatic breast cancer, a deadly disease that requires imminent new treatment options,” Nader Pourhassan, PhD, president and CEO of CytoDyn, said in a press release.

The filing was also supported by data from a second patient dosed with leronlimab under an emergency investigational new drug (IND) application granted by the FDA in September 2019. The patient had HER2-positive metastatic breast cancer, and showed no sign of new metastases in the liver, lung, and brain during treatment with leronlimab.

“This strong data confirms the power of leronlimab as a CCR5 inhibitor for patients living with mTNBC, and is clearly replicating early animal study results that demonstrated 98% elimination of metastases,” said Bruce Patterson, MD, CEO and founder of IncellDx, an adviser to CytoDyn.

“Our collective team of key opinion leaders believes that all patients with similar cancers in regards to CCR5 expression may also benefit from the use of leronlimab, including melanoma, brain, throat, lung, stomach, breast, ovarian, uterine, pancreatic, bladder, and thyroid cancer patients,” Patterson said, adding that leronlimab’s mechanism of action may also have potential in autoimmune diseases.

To date, CytoDyn has enrolled four patients, including two in the Phase 1b/2 trial and an additional two under the emergency IND protocol.

This trial, aiming to enroll 48 participants, is underway at the Quest Clinical Research in San Francisco, Northwestern University Feinberg School of Medicine, Houston Methodist, Vanderbilt University, and the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Hospital. More information can be found here.

“Our thought leaders believe that leronlimab may have the potential to treat over 20 different cancer indications and at least 10 autoimmune diseases, including graft versus host disease (GvHD) and NASH [non-alcoholic steatohepatitis],” Pourhassan said. “Based on the number of indications we intend to pursue, we believe we have one of the broadest platform technologies in biotech and are extremely excited to accelerate development of future indications.”

The FDA has already cleared CytoDyn to proceed with Phase 2 trials for both GvHD, a complication of stem cell transplants, and NASH, a common liver condition.

“We look forward to working with the FDA and continuing to provide additional data that further supports leronlimab as a potential treatment option for patients,” Pourhassan said.