Promising new treatment for glioblastoma multiforme (GBM) and other malignant gliomas
September 3, 2021
FDA has granted Lantern Pharma’s LP-184 (hydroxyureamethylacylfulvene) Orphan Drug Designation (ODD) for the treatment of glioblastoma multiforme (GBM) and other malignant gliomas on August 30, 2021. #glioblastoma #glioma #GBM
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Acylfulvenes is a cytotoxic agent which was naturally derived from Illudin S, a toxin from poisonous mushroom, Omphalotus olearius or commonly known as Jack O’lantern mushrooms. A couple of decades ago, a group of scientists discovered that acylfulvenes caused cell death when it was added to cancer cells in petri dishes. Thus, there was a huge interest to develop an anti-cancer drug using acylfulvenes to treat cancer patients, but ultimately, it did not yield any encouraging clinical results at that time.
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Fast forward, Lantern pharma has been developing a small molecule pro-drug and next generation of acylfulvenes, LP-184 or hydroxyureamethylacylfulvene. Using artificial intelligence and genomics, the company identified the biomarkers* that can pinpoint patients who are most likely to respond to LP-184.
(*Biomarkers are any genetic mutations or proteins which indicate whether a certain drug may be effective to treat cancer. )
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As mentioned above, LP-184 is a pro-drug which means that the original form of the drug is not active and needs to be converted in the body to be an active drug. In case of LP-184, it needs to be metabolized by an enzyme called PTGR1 (Prostaglandin reductase 1) to become an active drug. The active drug then binds and damages DNA in cells. Although all the normal cells have PTGR1 protein, some cancer cells from lung cancer, pancreatic cancer and GBM have increased amounts of the PTGR-1 protein compared to normal cells. Thus, LP-184 can be converted to an active drug and damage DNA more readily in cancer cells. Normally, cells have a system that can repair DNA damages, but some cancer cells have gene mutations in the DNA repair system. When treated with LP-184 in these cancer cells, they cannot overcome DNA damages and be led to cell death via a process called apoptosis.
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By identifying cancer patients with high amounts of the PTGR1 protein and mutations in the DNA repair system, LP-184 may show significantly enhanced activity and substantially less toxicity in the group of patients with pancreatic cancer and GBM.
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This is such welcome news to GBM patients. Only 25% of GBM patients survive more than one year, and only 5% of them 5 years. Thus, there is such a high unmet need to develop an efficacious treatment(s) for GBM. We anticipate that we will hear the announcement of clinical trials with LP-184 for the GBM patients and will post the news as soon as we hear it.
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But remember that the eligible patients for LP-184 should have high amounts of the PTGR1 protein and mutations in the DNA repair system in their cancer cells. We always emphasize the importance of tumor genomic profiling. Like LP-184, more and more companies are focusing on developing anti-cancer drugs to target patients with specific genetic make-ups to ensure the best response and highest safety. Thus, it is crucial to look at specific gene mutations in cancer cells when one is diagnosed with cancer. Please discuss tumor genetic profiling test with your oncologist. If you have any problem with obtaining the test, a non-profit organization, Soteria Precision Medicine Foundation (soteriaprecisionmedicine.org) can help you.
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What does mean that LP-184 was granted orphan drug designation for GBM?
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Orphan diseases are rare diseases which affect fewer than 200,000 people (one in every 1,500 people) nationwide. Glioblastoma is the most common and deadly brain cancer in adults; however, it affects 2-3 in every 100,000 people and thus is considered as an orphan disease. Because of the low number of patients, drugs for the rare diseases would not be profitable for companies. Thus, in 1983, Congress passed The Orphan Drug Act (ODA) to encourage pharmaceutical and biotech companies to develop treatments for rare diseases such as Huntington’s disease. When the FDA grants orphan drug designation or orphan status, companies are awarded certain financial benefits such as tax credits off clinical trial costs and exclusive marketing, so that they will be more eager to develop drugs for rare diseases. We anticipate that orphan drug designation of LP-184 will accelerate clinical testing of the drug for the treatment of GBM patients.