- The Food and Drug Administration has put a clinical hold on all U.S. studies of Bellicum Pharmaceutical Inc.'s lead candidate after three patients developed encephalopathy, possibly due to treatment with the drug.
- Bellicum's BPX-501 is under investigation in patients who underwent haploidentical hematopoietic stem cell transplants. Of the patients who experienced encephalopathy, one had a history of primary immunodeficiencies and caught two concurrent viral infections, though it's unclear whether the infections happened before or after transplant, according to Jefferies analyst Biren Amin. The patient later died due to brain damage.
- The other two patients' symptoms resolved over time. While investigators initially deemed those symptoms as not related to BPX-501 treatment, they were reclassified following the patient death.
Bellicum stock hit a record low on news of the clinical hold. Shares of the Houston-based biotech started trading on the NASDAQ in late 2014, initially priced at $19 apiece and amounting to a $140 million initial public offering.
Yet by Wednesday morning, Bellicum shares were going for $5.21 apiece, down more than 36% from the prior day's close.
Despite the hold, Jefferies' Amin maintained a "Buy" rating on Bellicum, noting that even if the three cases of encephalopathy are related to BPX-501, it's still safer for patients to receive the drug than to not. A previous study that looked at a 10-year cohort of 405 pediatric patients who received allogeneic transplants found 26, or 6%, had experienced encephalopathy. Among those patients, one died from progressive encephalopathy and 16 died from primary disease or toxicity.
"The incidence of encephalopathy AEs of BPX-501 therapy is at 1.25% (3/240), lower than 6% incidence observed in patients receiving [allogenic] transplants. We think the FDA clinical hold will remain for 1-3 months and therefore our rating remains," Amin wrote in a Jan. 31 investor note.
Bellicum disclosed that the clinical hold doesn't affect its pivotal Phase 1/2 BP-004 trial, which is taking place in Europe and evaluating BPX-501 in more than 100 pediatric patients who received an alpha/beta T-cell and CD19+ B-cell depleted haploidentical hematopoietic stem cell transplant. Bellicum notified the European Medicines Agency about the encephalopathy events, Amin wrote, and is waiting for word from the FDA on the next steps for the U.S. BPX-501 trials.
"These three cases are complex, with a number of potential confounding factors — including, in certain of the cases, prior failed transplants, prior history of immunodeficiency, concurrent infection, and administration of rimiducid in combination with other medications. Bellicum is working with FDA to evaluate the risk of encephalopathy in patients receiving BPX-501," the biotech said in a Jan. 30 statement.
According to Amin, two of the three patients who experienced encephalopathy received transplants prior to the study.