enGene announced positive results from its LEGEND Phase I/II clinical trial for treating high-grade NMIBC in patients with carcinoma in situ that are unresponsive to BCG treatment.
enGene, a clinical-stage biotechnology company that pioneers novel non-viral gene therapies, announced positive results from its LEGEND study.
The LEGEND study is the first-in-human Phase I/II clinical trial of EG-70 for the treatment of high-grade Non-Muscle Invasive Bladder Cancer (NMIBC) in patients with carcinoma in situ (CIS) who are unresponsive to Bacillus Calmette-Guérin (BCG) treatment, the most common immunotherapy for treating early-stage bladder cancer.
Non-Muscle Invasive Bladder Cancer is the sixth most common cancer in the United States and is often diagnosed in men ages 75-84. This type of cancer specifically affects the tissue that lines the inner surface of the bladder while the muscle is not involved. Symptoms of NMIBC include blood in the urine, frequent and urgent urination and pain in the lower abdomen and back.
The most common treatment for the disease, BCG, is an immunotherapy that utilizes the bacteria Mycobacterium bovis, the causative agent for tuberculosis in cattle related to the bacteria Mycobacterium tuberculosis, which causes tuberculosis in humans. BCG treatment does not cause severe disease in patients who are treated. Instead, the therapeutic is delivered via a soft catheter into the bladder to directly expose cancer cells to the drug. Once exposed, the immune system is activated, and cells are attracted to attack the cancer cells.
Although the treatment can be effective in stopping malignant growth and spread, 60% of patients treated may experience disease recurrence or progression, leading to an urgent unmet medical need. Currently, when BCG treatment fails, patients may undergo a radical cystectomy, a procedure that removes the bladder and surrounding organs to prevent further cancer spread.
Now, enGene is hoping to provide another solution for patients with its therapeutic EG-70. EG-70 is a novel, non-viral gene therapy that encodes two RIG-1 agonists, proteins that produce immune responses, to stimulate the innate immune system and IL-12, an interleukin that promotes pro-inflammatory signals to activate the adaptive immune system. By utilizing both arms of the immune system, the drug shows promising tumor regression with induction of effective immunological memory.
Results from the LEGEND study, which has a current enrollment of 222 patients, showed that the drug is safe, well-tolerated and shows encouraging clinical efficacy in high-grade NMIBC patients with CIS in whom BCG therapy has failed. Five of the six patients who have reached the 3-month efficacy assessment have achieved complete response.
The company indicated that no serious adverse events or dose-limiting toxicity had been observed. Adverse events related to the therapy included intermittent pain while urinating, urinary tract pain, restlessness, and low back pain.
“We are thrilled to announce the safety and clinical efficacy of EG-70 in patients with BCG-unresponsive NMIBC who are facing bladder removal as an alternative,” said Jason Hanson, chief executive officer at enGene. “EG-70 was designed ab initio as an intravesical monotherapy that would slot directly into current medical practice to provide ease-of-use and increased access to patients. With the initial results providing a clear best-in-class trajectory, we are confident that EG-70 will be the organ-sparing solution that is a game-changer for patients and physicians.”
The open-label trial has a primary endpoint of safety and tolerability and a key secondary endpoint of complete response at three months, with initial data supporting successful completion.
The positive data announcement arises amidst other positive clinical trial data in the treatment of NMBIC, including UroGen’s Phase III clinical trial of UGN-102, which has provided durable responses in those with low-grade intermediate-risk NMIBC. CG Oncology has also reported that its drug CG0070 in combination with Keytruda (pembrolizumab) showed complete efficacy in patients after three months in their Phase II trial.
