FDA Grants Orphan Drug Designation to LP-184 for Glioblastoma Multiforme and Malignant Gliomas

The FDA has granted an orphan drug designation to LP-184 as a potential therapeutic option for patients with glioblastoma multiforme and other malignant gliomas, according to an announcement from Lantern Pharma.¹

The next-generation alkylating agent was developed to preferentially damage DNA in tumor cells that overexpress select biomarkers or that harbor mutations in DNA repair pathways.² Data from preclinical studies have demonstrated that treatment with the small molecule drug candidate resulted in significantly enhanced antitumor activity with a substantial reduction in toxicity vs earlier-generation acylfulvenes.

Prior analyses have identified that those with glioblastoma multiforme and elevated PTGR1 expression and harboring defects in DNA damage repair components may represent a subset of genetically defined patients who could derive potential benefit from LP-184.

“Glioblastoma multiforme represents an important, underserved clinical opportunity, with a significant unmet medical need,” Panna Sharma, president and chief executive officer of Lantern Pharma, stated in a press release. “This second orphan drug designation from the FDA for the LP-184 program marks another major milestone and is further validation of the power of our data-driven approach to oncology drug development, aimed at more targeted and effective oncology therapies.”

In preclinical research conducted in partnership with Johns Hopkins, LP-184 was found to result in more than 106% tumor growth inhibition in 2 subcutaneous xenograft models of glioblastoma multiforme: U87 and M1123.³ The agent was also found to extend survival in mice who had an intracranially-implanted tumor model of the disease (U87) vs those that did not receive any drug.

When LP-184 was administered intravenously over 2 cycles, the agent reduced subcutaneous xenograft tumor volume in mice by more than 85%. In the orthotopic glioblastoma multiforme xenograft tumor model in mice, a single cycle of the drug led to a statistically significant extension of median overall survival (42 days) vs the control group (33 days; P < .0001).

“We believe LP-184’s ability to cross the blood–brain barrier, together with its antitumor efficacy and sensitivity correlations with relevant biomarkers, highlight LP-184’s potential to be used as both monotherapy as well as a synergistic agent in combination with other drugs to address the unmet needs in glioblastoma multiforme and other aggressive central nervous system tumors,” Sharma added in the press release.

Previously, in August 2021, the FDA granted an orphan drug designation to LP-184 for use in the treatment of patients with pancreatic cancer.⁴ Preclinical data with the agent showed that it resulted in significant and rapid tumor shrinkage by over 90% in in-vivo mouse models in 8 weeks.⁵ Tumors in mice that did not receive treatment were noted to grow in volume by eleven-fold during the same time period.

The agent was also found to have activity in 6 pancreatic cancer cell lines and 5 additional patient-derived xenograft ex-vivo tumor models. Across all cell lines and models, LP-184 substantially reduced cancer cells and cell growth; IC50 values were in the nanomolar range of 45 nM to 270 nM.

An agreement between Lantern Pharma, Kennedy Krieger Institute, and Johns Hopkins is dedicated to further advancing the potential of the agent as an option for patients with glioblastoma multiforme, particularly in areas of unmet need, such as those with MGMT-unmethylated, temozolomide-resistant disease and those with EGFR-mutated or recurrent disease.

References

1. FDA grants Lantern Pharma additional orphan drug designation for drug candidate LP-184 in glioblastoma multiforme & malignant gliomas. News release. Lantern Pharma. August 30, 2021. Accessed August 30, 2021. https://prn.to/3BpUwEV
2. Lantern Pharma oncology drug portfolio. Lantern Pharma. Accessed August 30, 2021. https://bit.ly/3BsD2YG
3. Lantern Pharma announces positive preclinical data in glioblastoma (GBM) with drug candidate LP-184 and expands GBM research collaboration. News release. Lantern Pharma. August 19, 2021. Accessed August 30, 2021. https://bit.ly/3BrAx8I
4. FDA grants Lantern Pharma orphan drug designation for drug candidate LP-184 in the treatment of pancreatic cancer. News release. Lantern Pharma. August 11, 2021. Accessed August 30, 2021. https://bit.ly/3Bpj291
5. Lantern Pharma announces significant positive preclinical data in pancreatic cancer with drug candidate LP-184. News release. Lantern Pharma. July 20, 2021. Accessed August 30, 2021. https://bit.ly/3yV3hWL