VOR33 is currently in clinical development and at this time has not been approved by the FDA for blood cancer treatment. VOR33 was granted fast track designation by the FDA on September 13th, 2021. Fast track is a process designed to facilitate the development, and expedite the review of drugs to treat serious conditions and fill an unmet medical need. The purpose is to get important new drugs to patients earlier.
For many AML patients, the only way to achieve a long remission or cure is by undergoing an allogeneic stem cell transplant. Unfortunately, for many people with high-risk AML, relapse is common even after receiving a transplant. Between 2013 and 2017 there were about 16,000 allogeneic stem cell transplants completed in the United States for the treatment of AML. Despite this, around 40% of AML patients relapse within two years of their transplant and face an extremely poor prognosis, with two-year survival rates of less than 20%. While there are targeted treatment options for relapsed individuals after transplant, the effectiveness of these therapies are limited because they target both the AML cells and the patient’s newly engrafted healthy cells. This effect is called “on-target toxicity.” Patients at high risk of relapse need better options post-transplant to keep the AML from returning.
Many blood cancer treatments rely on identifying proteins expressed by cancer cells. For example, many treatments like antibody-drug conjugates, CAR-T cells and bispecific antibodies can be designed to target cell surface proteins like CD33, CLL1 and CD123 which are commonly found on AML cells. CD33 is a cell surface protein that is present in more than 80% of patients with AML, making it a great drug target.
Targeting these proteins results in cancer cell death but most targets like CD33 are also found on healthy cells which leads to on-target toxicity. These treatments also destroy healthy bone marrow cells and lead to less than ideal outcomes. On-target toxicity could force patients to come off therapy and significantly limit treatment options post-transplant because the bone marrow is fragile during this time. To address this challenge, VOR33 aims to protect healthy cells while killing only the cancer cells.
In order to introduce treatment-resistant cells into the bone marrow of an AML patient, cells are first taken from a healthy, matched donor. These cells are genetically modified to delete the gene that makes the CD33 protein and then infused into the patient. These cells engraft into the bone marrow and produce more cells that do not make the CD33 protein. These healthy cells become invisible to cancer therapies like Mylotarg (gemtuzumab ozogamicin) which targets CD33. This ensures only cancer cells are destroyed and the healthy cells are protected. After infusion of the genetically altered stem cells, gemtuzumab, the anti-CD33 therapy can be given to help reduce the risk of post-transplant relapse. Because the healthy cells are now hidden due to their lack of CD33 expression, this drug will attack only the AML cells that still have the target protein.
A clinical trial looking at VOR33 infusion followed by Mylotarg is beginning to recruit. You can learn more about this trial by visiting our:
To watch a video that explains more about how VOR33 works, visit Vor Biopharma’s website
about the author
Katie joined the HealthTree Foundation as the Community Director for AML in 2021. She is a registered dietitian who previously worked at the VA hospital in Dallas, Texas where she coached veterans with blood cancer on how to use nutrition to improve their treatment outcomes and minimize cancer-related side effects. Katie is passionate about health education and patient empowerment. In her spare time, she loves to experiment with new recipes in the kitchen, spend time running outdoors and travel to new places.