Patient Death in Poseida Prostate Cancer Study Prompts Clinical Hold

A Phase 1 trial testing a Poseida Therapeutics cell therapy in men with prostate cancer is on hold after a patient enrolled in the study died of liver failure nearly three weeks after receiving the treatment.

The San Diego company, which has touted its product candidates as safer than early-generation versions developed by other companies, announced the FDA’s decision to pause the study on Monday.

Poseida (NASDAQ: [[ticker:PSTX]]) is evaluating P-PSMA-101, a chimeric antigen receptor T-cell (CAR-T) therapy, in patients with prostate cancer that has spread beyond its initial location and stopped responding to drugs intended to lower levels of the male sex hormones that drive the cancer. The treatment is an autologous one—created from a patients’ own immune cells, which are engineered in a laboratory to better fight cancer before being reinfused.

The patient who died in the trial received P-PSMA-101 in late July following prior treatment with multiple cancer drugs, according to a regulatory filing. Poseida, in the filing, said there were no side effects in the first seven days after treatment. But subsequently, symptoms arose that led to hospitalization, and the patient died 19 days after treatment. In the regulatory filing, Poseida noted that he attended a follow-up visit a week following the treatment but missed two subsequent visits, during which time the symptoms developed. The patient’s death, according to the clinical investigator, is “possibly related to P-PSMA-101 pending further investigation,” the filing says.

The biotech, in the filing, said while the cause of the patient’s death has not been confirmed, his symptoms were consistent with an overreaction of the immune system known as macrophage activation syndrome (MAS), in which the body produces and activates too many T cells and macrophages. MAS has been associated with CAR-T therapies; other potential causes include infection and autoimmune disease. The patient also developed a form of eye inflammation called uveitis, which caused blurred vision.

According to Poseida, no other patients in the study experienced decreased vision, uveitis, MAS, or liver failure. There also haven’t been any incidents of cytokine release syndrome or neurotoxicity, two potentially life-threatening side effects closely associated with CAR-T therapy.

But the patient death calls into question the company’s approach to creating a CAR-T product that’s safer than earlier iterations. The company has said the safety profile of its products is intended to allow them to be administered on an outpatient basis, which could significantly reduce their cost. Approved CAR-T products currently must be administered in a hospital so patients who react poorly have access to intensive care.

Poseida’s therapies include a high percentage of a type of T cell called memory stem (TSCM) cells, which the company believes kills tumor cells more gradually and could reduce the potential for side effects. Tools the company has developed to improve the safety profile of its CAR-T candidates include a proprietary “safety switch” that provides the option of eliminating some or all of the engineered cells in the event a patient does not tolerate them well. The mechanism is activated by the administration of a small molecule. But the company said in a regulatory filing that as of March 31 it hadn’t had to use it, and a company spokesperson declined to comment on whether the switch had been deployed since then or whether it was used in the case of the patient who died, citing the ongoing investigation.

Poseida said once findings are complete, the information will inform a plan that it intends to submit to the FDA requesting permission to resume the trial. Once the filing is submitted and any questions from the FDA have been answered, the agency will have 30 days to rule whether the study may restart.

The company’s other investigational CAR-T, P-BCMA-101, remains under evaluation in Phase 2 testing for patients with multiple myeloma that hasn’t responded or has stopped responding to treatment. The other programs the company is advancing are allogeneic, or “off-the-shelf,” treatments, created from cells donated by healthy volunteers rather than from patients themselves.

The clinical hold comes less than a month after the biotech began trading on the Nasdaq. Shares in the company plunged 30 percent on Tuesday to $9.06. When it made its public debut in July, Poseida priced its shares at $16 apiece.

In its IPO, the company raised $244 million, money primarily intended to cover trial costs and manufacturing expenses associated with its pair of clinical-stage candidates. The last round of outside financing the company raised before its IPO totaled $110 million. That financing followed a $142 million haul 14 months prior, a round that was led by Novartis (NYSE: [[ticker:NVS]]).

Image: iStock/Maximkostenko