Olaptesed Pegol Gains FDA Clearance in Glioblastoma


The FDA approved the investigational new drug application for olaptesed pegol as a potential treatment for adult patients with aggressive brain cancer, specifically glioblastoma.

  • Data from the GLORIA study (NCT04121455) demonstrated that olaptesed pegol (NOX-A12) plus bevacizumab (Avastin) and radiotherapy led to a median overall survival (OS) of 19.9 months in patients with glioblastoma.
  • TME Pharma intends to proceed with a phase 2 study involving approximately 100 patients with newly diagnosed, chemotherapy-resistant glioblastoma with measurable residual tumors after surgery.
  • The company has also submitted a fast track designation request to the FDA to expedite the regulatory pathway for the agent in glioblastoma, with expectations of a decision by the end of March 2024.

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The FDA cleared the investigational new drug (IND) application for olaptesed pegol as a potential treatment for adult patients with aggressive brain cancer.1

Recent findings from the phase 1/2 GLORIA study showed that olaptesed pegol had a median OS of 19.9 months when given in combination with bevacizumab and radiotherapy in patients with glioblastoma who had measurable chemotherapy-resistant residual tumors postsurgery.2 In the olaptesed pegol, bevacizumab, and radiotherapy cohort, the 19-month survival rate was 10 times greater than a matched reference cohort receiving the standard of care (50% vs 5%, respectively).

Now that the IND is open at the FDA, the company plans to proceed with the continued clinical development of olaptesed pegol within a randomized, controlled, phase 2 study where approximately 100 patients with newly diagnosed, chemotherapy-resistant glioblastoma who have a residual measurable tumor after surgery will be evaluated. Initiation of the study is expected to be later this year.1

"Receiving approval of the FDA for the design of our phase 2 clinical trial in glioblastoma provides a clear roadmap to potential industrial partners and investors on the next steps in clinical development. The discussions with the FDA have been constructive and have allowed us to design a robust phase 2 that should provide us with solid evidence of the highly differentiated profile of [olaptesed pegol] in combination with bevacizumab in newly diagnosed, chemotherapy-resistant glioblastoma patients. The open IND will also allow us to expand our clinical development into the [United States], where we expect to generate significant interest in the medical community," said Aram Mangasarian, chief executive officer of TME Pharma, in a press release.

Human brain: ©Sergey Nivens - stock.adobe.com

Human brain: ©Sergey Nivens - stock.adobe.com

In the phase 2 study, experts will evaluate the optimal dosing regimen and the respective contributions of each component to the overall effectiveness of the combined therapy. This evaluation will enable TME Pharma to optimize late phase development by examining various dose levels of olaptesed pegol alongside bevacizumab in a patient population randomized to standard of care.

The FDA-approved study design of this trial, based on discussions with the FDA and further interaction during the IND application process, will include 5 arms. Twenty patients will be enrolled per arm.

  1. Arm 1, olaptesed pegol will be given at 200 mg per week with radiotherapy and bevacizumab.
  2. Arm 2 will get olaptesed pegol 400 mg/week plus radiotherapy and bevacizumab.
  3. Arm 3 will receive olaptesed pegol 600 mg/week plus radiotherapy and bevacizumab.
  4. Arm 4 will get olaptesed pegol at a dose of 600 mg/week with radiotherapy alone.
  5. Arm 5 will get the standard of care, which consists of temozolomide and radiotherapy.

Alongside the IND submission, a fast track designation has been submitted by TME Pharmato the FDA, aiming to secure an accelerated regulatory pathway for the agent as a treatment option in glioblastoma. The company anticipates receiving the FDA's decision before the end of March 2024.

"We also expect to receive the FDA’s decision regarding fast track designation for [olaptesed pegol] in glioblastoma in the next few weeks, which can further strengthen our regulatory position in the [United States] and should help us in the search for industrial and financial partners who can assist TME Pharma in bringing [olaptesed pegol] to patients in the quickest way possible,” said Mangasarian in a press release.1

1. TME Pharma announces FDA clearance of investigational new drug (IND) application for NOX-A12 phase 2 trial in brain cancer. News release. TME Pharma N.V. March 5, 2024. Accessed March 5, 2024. https://tinyurl.com/5t3zvayv
2. TME Pharma announces further improvement in median overall survival at 19 months follow-up in GLORIA brain cancer trial. News release. TME Pharma. December 20, 2023. Accessed March 5, 2024. http://tinyurl.com/yc27wz5m

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