BPX-501 is a T-cell-based therapy developed by Bellicum Pharmaceuticals for patients with blood cancers and inherited orphan blood disorders who have undergone hematopoietic stem cell transplantation (HSCT).

The U.S. Food and Drug Administration (FDA) granted orphan drug status to the combination of BPX-501 and rimiducid as a replacement T-cell therapy in February 2016, for the treatment of immune deficiency and graft-versus-host disease (GvHD) after partially-matched HSCT. This was followed by the European Commission (EC) granting orphan drug designations to BPX-501 for the treatment of HSCT and rimiducid for the treatment of GvHD, in August 2016.

How BPX-501 works

BPX-501 consists of T-cells, which are derived from a partially-matched donor (for example a relative of the patient). These T-cells are grown in the laboratory and a “suicide” gene called inducible caspase 9 (iCasp9) linked to a rimiducid-binding domain is introduced into them so that they are killed when they encounter rimiducid.

Since strong doses of chemotherapy are given to patients prior to HSCT to weaken the immune system, these donor-derived T-cells are beneficial due to their potential to help the immune system recover faster. But there is an increased risk that they may start attacking the patient’s healthy tissues, resulting in GvHD. To prevent GvHD, these T-cells are genetically modified with the iCasp9 gene that acts as a safety switch. In case GvHD develops, rimiducid can be administered and induce the production of caspase 9, therefore, causing the death of the T-cells.

Thus, BPX-501 is administered following HSCT to potentially help the immune system recover faster after transplantation, reduce the occurrence of viral infections, and enhance the immune response against the patient’s cancer cells (graft-versus-leukemia effect) without the risk of GvHD.

BPX-501 in clinical trials

An ongoing study called BP-004 is evaluating the safety and effectiveness of BPX-501 in children with cancerous or non-cancerous blood cell disorders who are having a blood stem cell transplant depleted of T-cells. The study includes a Phase 1/2 trial (NCT02065869), which is recruiting participants in Italy, Span, and the U.K. and an extension trial (NCT03301168) recruiting participants in the U.S.

So far, data from 98 patients show that treatment with BPX-501 led to a rapid immune recovery, a low incidence of transplant-related deaths, a reduction in viral infections, and a low rate of GvHD that was manageable with either standard treatments or rimiducid.

Data from a sub-group of 47 patients with acute leukemia show that the treatment resulted in rapid immune system recovery, strong anti-cancer effect, and low rates of relapse.

Two ongoing trials, the DOTTI trial (NCT01494103) and the CASPALLO trial (NCT00710892), aim to study the safety and effectiveness of BPX-501 following HSCT in patients with blood disorders or cancers. Data from both studies show that BPX-501 administered 30 days after T-cell depleted HSCT improved immune recovery and reduced viral infections. A single dose of rimiducid was able to resolve acute GvHD, which developed in eight of 22 patients, within 24-48 hours. The administration of rimiducid preserved anti-viral immunity and the patients required no further treatment. Both studies are ongoing, but no longer recruiting participants.

Two ongoing Phase 1/2 studies, the BP-001 study (NCT01744223) and the BP-005 study (NCT02487459), aim to evaluate the safety of BPX-501 after partially-matched HSCT in adults with blood cell cancers. The BP-001 study is recruiting participants across the U.S. and is expected to be completed in March 2018. The BP-005 study will be conducted at the MD Anderson Cancer Center in Houston, Texas, but is not yet open for patient recruitment. It is expected to be completed in December 2021.

The BP-003 study (NCT02231710) is a single site study in children with inherited orphan blood disorders in which BPX-501 is administered after partially-matched HSCT. The study is being conducted at the Fred Hutchinson Cancer Research Center in Seattle, Washington, and is expected to be completed in December 2019.

The BP-008 study (NCT02477878) aims to study increasing doses of BP-501 to treat the return of blood cancers in adults and children after the transplant. The study also aims to determine a dose of rimiducid that can resolve uncontrolled GvHD while preserving the anti-cancer effect of BP-501. The study is recruiting participants across the U.S. and is expected to be completed in December 2020.


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