Orphan Drug Designations from the FDA for Cannabis Compounds as Cancer Treatments

The Food and Drug Administration (FDA) defines a rare disease as one affecting less than 200,000 people. However, because there are over 7,000 different rare diseases, over 30 million people in the United States are classified as having one, and most rare diseases do not have any FDA-approved treatments. To encourage the development of drugs intended to treat rare diseases, also known as orphan diseases, the Orphan Drug Act (ODA) was passed in 1983. The ODA provides companies researching pharmaceutical treatments for rare diseases with incentives, such as tax credits, certain fee waivers, and market exclusivity. When a specific treatment is granted orphan drug designation (ODD), these incentives are activated. After ODD is obtained, a company must still undertake the standard process for having a drug approved, including conducting clinical trials to prove safety and efficacy. ODD status essentially decreases the expense and risk associated with drug development for rare diseases.

A key requirement in the FDA’s ODD application is a summary of all relevant scientific data, including preclinical and clinical studies. Without a reasonable level of medical plausibility that a treatment would actually work against the targeted rare disease, there would be no justification to grant ODD. While such designation does not guarantee a drug will end up as a viable treatment, it does suggest a therapy has at least a minor chance of working in humans. Therefore, the fact that numerous cannabis-associated drugs have been granted ODD for the direct treatment of various cancers is a testament to the real potential of cannabis compounds, primarily cannabinoids, as cancer therapies.

No cannabis products intended to treat cancer have been approved by the FDA yet, but the fact that so many have been granted ODD makes it hopeful that one of them may be approved sometime in the next five years. The first apparent designation ever granted for a cannabinoid as an anticancer agent occurred on August 20, 2014 for Benuvia Therapeutics. It concerned cannabidiol (CBD) as a treatment for glioblastoma multiforme, one of the most aggressive brain tumors. The full appearance of the designation on the FDA’s website is featured below, while smaller screenshots are subsequently featured.

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The next ODD for a cancer application of CBD was also granted to Benuvia Therapeutics, except the designation was for the treatment of glioma more broadly rather than glioblastoma multiforme specifically, which is an advanced glioma.

GW Pharmaceuticals (also listed as GW Research Ltd.) is the creator of Epidiolex, the FDA-approved cannabis-derived CBD-rich pharmaceutical product intended to treat seizures associated with rare epileptic conditions like Dravet syndrome. Interestingly, Epidiolex started out as a drug with ODD for treatment of Dravet syndrome, and it successfully moved from simple designation to full-scale approval after clinical trials were completed. This example shows it is possible for a cannabis-based drug to be approved through this framework.

GW Pharmaceuticals has also been exploring the potential of cannabinoids to treat cancer, particularly glioblastoma. The preliminary results of a controlled trial published in 2017 showed that combining tetrahydrocannabinol (THC) and CBD with chemotherapy effectively extended the lives of glioblastoma patients, with median survival of 550 days in the cannabis-treated group, and 369 days in the placebo group that only received chemotherapy. Not surprisingly, GW received ODD for the treatment of glioma with THC and CBD back on December 3, 2015.

In addition to the above clinical trial, significant preclinical evidence suggests THC and CBD could fight glioma. One of the first studies indicating an anticancer effect of THC was published in 1998 and showed that it induced apoptosis in glioma cells. CBD was also shown to induce apoptosis in glioma cells in 2004 by Italian researchers. Both cannabinoids were further demonstrated to synergize with each other to produce greater-than-additive anticancer effects against glioblastoma cells in a 2010 study.

Another company called AXIUM Pharmaceuticals received ODD on January 8, 2018, for the use of THC and CBD to treat glioblastoma multiforme. More information on their progress toward approval is not apparent.

Yet another company exploring cannabinoids for the treatment of glioma is Diverse Biotech. They received ODD for CBD to treat glioblastoma on April 28, 2020. Several months later, they received another designation for CBD bonded with temozolomide, a standard chemotherapy drug for treating gliomas.

While most ODD filings relate to glioma brain tumors, there are two others that concern different cancers. On November 17, 2019, Tetra Bio-Pharma received ODD for the use of THC to treat hepatocellular carcinoma (HCC), the most common form of liver cancer. As THC has been shown to induce apoptosis in HCC cells and shrink HCC tumors in mice, it is certainly worth exploring whether these results could translate to humans.

Most of the medical attention related to cannabis has focused on cannabinoids like THC and CBD. However, other classes of compounds exist within the cannabis plant, including flavonoids. These compounds also possess tremendous medical promise, including potentially as cancer treatments. A study published in July 2019 by researchers from various universities in Massachusetts, including Harvard Medical School, found that a flavonoid derivative of cannabis known as FBL-03G induced apoptosis in pancreatic cancer cells and delayed pancreatic tumor progression in animals. This appeared to constitute at least partially the scientific rationale for the ODD granted to Flavocure Biotech for their cannabis-derived flavonoid drug, known as Caflanone (the brand name for FBL-03G).

With the wide range of ODDs granted to cannabis-based drugs, it is undeniable that the prospect of cannabis treating cancer is being taken seriously at the highest levels. Only with more clinical trials will any of these designations possibly be granted marketing approval, so hopefully they are conducted as quickly and thoroughly as possible.