MDNA55 has been granted Orphan Drug status by USFDA and EMA (European Medicines Agency) for the treatment of gliomas and Fast Track designation for the treatment of GBM and anaplastic astrocytoma (AA) by the USFDA. MDNA55 is currently in late stage development for the treatment of recurrent GBM, a uniformly fatal form of brain cancer.
In previously completed clinical studies 72 patients with recurrent or progressive malignant gliomas (GBM and AA) were treated with MDNA55. More than 40% of the recurrent GBM (rGBM) subjects had multiple relapses or large tumors (>4cm in diameter) and 25% had a poor performance status (Karnofsky Performance Score; KPS of <70) prior to treatment with MDNA55. In two sponsor-initiated Phase 1/2a trials, all patients received a single infusion of MDNA55 using convection enhanced delivery (CED). In the first study, tumors were not resected, whereas in the second study, the tumors were resected 3 weeks post-treatment. Tumor response analysis was only performed in the first study. An additional 46 patients have been treated in the ongoing Phase 2 clinical study for which we announced that enrolment was complete in April 2019.
To date, there have been no detectable levels of MDNA55 in the blood stream, nor any evidence of significant systemic toxicity following treatment. There have been no deaths attributed to MDNA55. Adverse events (AEs) have been primarily neurological which were generally transient and an aggravation of pre-existing neurological deficits anticipated in this patient population.
Medicenna has recently completed enrolment in a Phase 2 clinical trial with MDNA55 for the treatment of rGBM at nine clinical sites in the United States.
The Phase 2 clinical trial, using enhanced Convection Enhanced Delivery (“CED”) is a multi-center, open-label, single-arm study in up to 52 subjects and at least 46 intent to treat patients with first or second recurrence or progression of GBM after surgery or radiotherapy ± adjuvant therapy or other experimental therapies.
The primary endpoint of the study is median Overall Survival (mOS) comparing a null survival rate of 8.0 months (based on historical control) with an alternative pursue rate of 11.5 months (1-sided alpha = 0.10 and 80% power for 46 ITT subjects). The secondary endpoint is objective response rate (ORR) assessed by the modified Response Assessment in Neuro-Oncology (mRANO)-based criteria incorporating advanced imaging modalities according to a null response rate of 6% with alternative pursue rate of 18% (1-sided alpha = 0.10 and 80% power for at least 35 subjects evaluable for response). IL4R expression levels in tumor biopsies and their potential impact on patient outcomes following treatment with MDNA55, were and are being retrospectively evaluated.
Current Study Results:
On February 7, 2019 Medicenna presented new clinical study results in a podium presentation entitled, “The IL4 Receptor as a Biomarker and Immunotherapeutic Target for Glioblastoma: Preliminary Evidence with MDNA55, a Locally Administered IL-4 Guided Toxin” by John H. Sampson, MD, PhD, Robert H. and Gloria Wilkins Distinguished Professor and Chair of Neurosurgery at Duke University during the 5th Annual Immuno-Oncology 360o Conference held in New York, NY. Following treatment with MDNA55 at the low dose, the IL4R positive group showed a remarkable increase in mOS of 15.2 months when compared to 8.5 months in the IL4R negative group. Survival rates at 6, 9, and 12 months were 100%, 67% and 55% versus 73%, 40%, and 30%, in the IL4R positive and negative groups, respectively. In addition, Dr. Sampson presented that irrespective of IL4R expression, mOS was 11.8 months in all patients following a single treatment with MDNA55 at the low dose with an overall survival rate of 89% at 6 months, 59% at 9 months and 46% at 12 months, substantially exceeding landmark mOS and survival rates reported for approved drugs for rGBM (mOS is 8 months for Avastin and Lomustine and survival rates at 6, 9 and 12 months are 62%, 38%, 26% and 65%, 43%, 30%, respectively). In these participants, patients with IL4R positive tumors showed a faster time to relapse (10.3 months) following initial diagnosis of GBM when compared to patients with low to no expression of IL4R (16.7 months) supporting published research showing that the Type 2 IL4R is a key biomarker for more aggressive forms of GBM.
On June 18, 2019, Dr. Fahar Merchant presented results from the Phase 2b MDNA55 clinical trial which recently completed enrollment (N=46) at the Inaugural Immuno-Oncology Pharma Congress in Boston, MA. The presentation highlighted disease control in up to 83% of the patients according to iRANO criteria (immunotherapy Response Assessment in Neuro-Oncology) which measures tumor response relative to the largest tumor size post-treatment (nadir). Use of advanced imaging techniques (such as perfusion and diffusion MRI) was able to show underlying tissue response amidst inflammation and edema in some subjects. In addition, safety data from the Phase 2b clinical trial show a similar safety profile to previous MDNA55 trials, with no systemic toxicities, no clinically significant laboratory abnormalities and no drug-related deaths.
Medicenna plans to have an End of Phase 2 (“EOP2”) meeting with the FDA in the second half of 2019 to discuss the results of the MDNA55 Phase 2b clinical study and the development pathway forward, including the possibility of seeking accelerated approval in patients with IL4R positivity which is considered to display a more aggressive form of rGBM. Medicenna expects to have twelve month survival data on all patients in the study by Q1 2020.