FDA Grants Orphan Drug Designation to WP1122 for Glioblastoma Multiforme

FDA

The FDA has granted an orphan drug designation to WP1122 as a potential therapeutic option for patients with glioblastoma multiforme, according to an announcement from Moleculin Biotech, Inc.¹

The investigative agent was developed as a 2-DG prodrug to offer a more favorable pharmacological profile. In preclinical models where tumor cells required greater glycolytic activity than normal cells, WP1122 was observed to have stronger potency than 2-DG alone.

The preclinical data reported with WP1122 illustrated the potential of the agent in this disease and supported the regulatory agency’s decision to grant it investigational new drug (IND) status.

The drug developer, Moleculin Biotech, Inc., is currently examining collaboration opportunities for the clinical development of WP1122.

“The receipt of orphan drug designation represents an important milestone for our promising WP1122 development program,” Walter Klemp, chairman and chief executive officer of Moleculin Biotech, Inc., stated in a press release. “Given the progress of our phase 1 clinical trial [NCT05195723] in healthy volunteers, the strong preclinical data supporting glioblastoma multiforme as 1 of many potential indications and the recent clearance by the FDA of IND status for WP1122 in [this disease], we believe this designation further supports the potential of WP1122 and is another step forward in further validating our deep pipeline.”

In the phase 1 study, investigators set out to explore the effects of a single dose and several days of dosing of WP1122 administered as an oral solution in healthy human volunteers.² To be eligible for enrollment, participants needed to be between the ages of 18 years and 55 years, fully vaccinated against COVID-19 and willing to undergo testing for the virus, have a minimum body weight of at least 50 kg for men and at least 45 kg for women.

Participants needed to be healthy per physician assessment and based on a medical evaluation, which included medical history, physical examination, laboratory tests, and echocardiogram.

Those who were pregnant, breastfeeding, or intending to become pregnant were excluded, as were those with evidence of SARS-CoV-2 infection, those with respiratory disease, hypersensitivity or severe allergic reactions to vaccines or drugs, diabetes mellitus, clinically relevant hypertension, history of bleeding diathesis or coagulopathy, or cardiovascular diseases.

Each study group is comprised of 10 volunteers who are randomly assigned 4:1 to receive WP1122 or placebo. Dose escalation will take place in sequential single-dose cohorts.

In the first portion of the study, the single ascending dose portion, 8 volunteers will receive the oral investigational drug and 2 will receive placebo. Up to 40 volunteers will be enrolled to this portion of the research.

The second portion of the study, or the multiple ascending dose portion, will start after the third group in the single dosing portion of the trial has completed dosing and WP1122 is found to be safe and well tolerated. In up to 4 groups, 8 volunteers will be administered oral WP1122 and 2 will be given placebo twice daily, 12 hours apart for the duration of 7 days. Up to 40 volunteers will be enrolled to this portion of the study.

The primary outcome measures for the trial are to evaluate the safety and tolerability of escalating doses of WP1122 given as a single oral dose in sequential cohorts of healthy volunteers and to determine the maximum tolerated dose of the agent. Investigators also want to analyze the safety and tolerability of 7 days of escalating doses of the agent given every 12 hours in sequential cohorts of healthy volunteers and to identify the recommended phase 2 dose for a trial being done in patients with COVID-19.

Secondary outcome measures include examining the activity of WP1122 in the body after a single dose and multiple ascending doses; to do this, investigators will examine participants’ maximum plasma concentration.

Glioblastoma multiforme represents the most aggressive malignant primary brain tumor; this disease continues to be incurable and those diagnosed with it have a median survival of only 15 months. Glioblastoma multiforme accounts for 54% of all glioma cases and 16% of all primary brain tumors.

With orphan drug status, the clinical-stage pharmaceutical company is provided with select benefits, such as financial incentives to support clinical development. Moleculin Biotech, Inc. also has the potential for up to 7 years of market exclusivity for WP1122 in the United States if the agent is eventually approved in its designated indication.

References

1. Moleculin receives FDA orphan drug designation of WP1122 for the treatment of glioblastoma multiforme. News release. Moleculin Biotech, Inc. September 6, 2022. Accessed September 7, 2022. https://bit.ly/3APGCNu
2. Study to assess the safety and pharmacokinetics of WP1122 in healthy volunteers. ClinicalTrials.gov. Updated May 13, 2022. Accessed September 7, 2022. https://clinicaltrials.gov/ct2/show/NCT05195723