Death of Patient Halts Clinical Trial That Involved California Stem Cell Agency

A clinical trial based on a $4 million award from the California stem cell agency has been suspended after one of the patients died.

The phase one safety trial was being conducted by Poseida Therapuetics, Inc., of San Diego.  In 2018, Poseida received $4 million for the proposed therapy from the California Institute for Regenerative Medicine (CIRM), as the stem cell agency is officially known. 

Clinical trials are the last stage before a treatment is approved by the federal government for widespread use. 

The death of the patient comes as CIRM supporters are backing a measure, Proposition 14, on the November ballot that would provide $5.5 billion more for the agency. 

CIRM is running out of the $3 billion provided in 2004, when it was created via a ballot initiative. It will begin closing its doors this fall without additional funding.

In response to a request for comment, the agency released the following statement:

"Our sympathy goes out to the family of the individual who died and to the team at Poseida. We know how deeply committed they are to the work they are doing and how big an impact moments like this have on researchers.

"We did fund the late stage pre-clinical research, but as we are not involved in this clinical trial itself we have no additional information. The (Food and Drug Administration) has put a hold on the trial to determine what happened and we will continue to follow the results of this matter very closely."

CIRM said in a 2018 news release that the proposed treatment was an effort to "supercharge a patient’s own immune system cells to attack and kill a treatment-resistant form of prostate cancer."

Maria Millan, CEO and president of CIRM, said in the news release:

“This is a promising approach to an incurable disease where patients have few options.

"The use of chimeric antigen receptor engineered T cells has led to impressive results in blood malignancies and a natural extension of this promising approach is to tackle currently untreatable solid malignancies, such as castrate resistant metastatic prostate cancer.

The $4 million was for work that immediately preceded the trial -- not the trial itself -- and led to the preparation of an Investigation New Drug (IND) program.  

On Feb. 28 of this year, Poseida initiated the phase one trial, which is aimed at determining the safety of the proposed treatment, according to documents filed with the federal government. The company hoped to enroll 40 patients. 

In a filing yesterday with the Security and Exchange Commission, Poseida said that the Food and Drug Administration had placed the trial on "clinical hold."

The company said, 

"Although the direct cause of the hepatic failure has not yet been confirmed, the patient developed symptoms consistent with macrophage activation syndrome (MAS). MAS is a serious and potentially fatal overactivation of the immune system which has been associated with CAR-T therapies, but can have other causes such as infection and autoimmune disease. 

"The patient also developed blurred vision which was diagnosed as uveitis. The clinical investigator has assessed the SAE (serious adverse event) as possibly related to P-PSMA-101 pending further investigation."

P-PSMA-101 is the name of the therapy involved. 

CIRM's summary of the review of Poseida's application (CLIN1-10999) in 2018 said the proposed therapy "had the potential to improve survival in this patient group, which faces a poor and fatal prognosis." 

It also said, 

"Some reviewers noted the potential for off-target toxicity with a PSMA CAR-T product, which should be carefully assessed in the clinical studies."

Here is the text of the discussion at the CIRM meeting at which the grant was approved. 

Poseida's stock price plummeted on the news. It closed yesterday $13.00 a share. As of this writing, it was trading at $9.01. 

Just this July, Poseida went public and has traded as high as $17.62. Prior to the stock offering, Novartis invested $142 million in the firm. The public offering valued the company at $1 billion.

CIRM has also backed Poseida with $20 million for a clinical trial involving a different approach for a disease called multiple myeloma. 

(Editor's note: An earlier version of this item did not carry the comment from CIRM, which came after the item was posted. Also added was the link to the CIRM discussion of the award in 2018.)