CLINICAL DEVELOPMENT

REGULATORY STATUS:

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.

PATIENTS:

To date 72 patients with recurrent or progressive malignant gliomas (GBM and AA) have been treated with MDNA55. More then 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.

SAFETY:

There were no detectable levels of MDNA55 in the blood stream, nor any evidence of significant systemic toxicity following treatment. There were no deaths attributed to MDNA55. Adverse events (AEs) were primarily neurological which were generally transient and an aggravation of pre-existing neurological deficits anticipated in this patient population.

EFFICACY:

In the non-resected study, single treatment with MDNA55 was associated with a tumor response rate of 56% with a complete response (CR) rate of 20%. Further, the disease control rate (including stable disease) was 68%. Responses and tumor stabilization were durable, with a median duration of disease stabilization and response being 16 weeks.

These findings are compelling when compared with response rates of less than 10% for historical controls and the 28% response rate that led to accelerated approval of Avastin. Further, among 25 unresected rGBM patients treated with MDNA55, an unprecedented CR rate of 20% was achieved when compared to 1.2% for Avastin. Similarly, Celldex recently reported a 6.9% CR rate for Rindopepimut when combined with Avastin (with or without surgery) in an enriched patient population (EGFRvIII positive). MDNA55 data are particularly promising given the poor baseline characteristics of the subjects.

FUTURE STUDIES

  • Enroll patients at first relapse with inclusion criteria consistent with contemporary rGBM clinical trials
  • Personalize treatment for patients that over-express the IL4R (76% of GBM population). Co-development of an IL4R companion diagnostic will proceed in parallel with clinical studies
  • Delivery of MDNA55 will employ regulatory approved high precision planning software and catheters designed specifically for CED of therapeutics into the brain tumor
  • Co-infusion of a surrogate tracer (an MRI contrast agent) will allow real-time monitoring of MDNA55 distribution ensuring adequate coverage of the tumor and the infiltrative edges

Compared to earlier studies, each of the above has the potential to improve MDNA55 distribution, its safety as well as efficacy.

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