Onconase (ranpirnase) is a novel agent being tested as a treatment for mesothelioma and other uses. The U.S. Food and Drug Administration (FDA) has not yet approved it for any use, but it may help manage mesothelioma. Rather than a potential cure, Onconase is an enzyme that stabilizes cancer cells and prevents tumor growth, slowing the progression of the disease.
What Is Onconase?
Onconase is the brand name of ranpirnase, a medication originally developed and manufactured by TamirBio. Orgenesis acquired TamirBio in 2020. Orgenesis continues to test ranpirnase in clinical trials.[1]
What Is Onconase Used to Treat?
TamirBio developed ranpirnase as a medication to treat viral infections. It has already shown promise in treating the human papillomavirus, HPV.
Onconase is not yet approved in the U.S. for treating any disease. This may change as more clinical trials show it can be safe and effective in other conditions. Many clinical trials have focused on using ranpirnase to treat cancer, including mesothelioma.
Ranpirnase is an enzyme, a large protein that modifies biological reactions, speeding them up or helping them get started. The medication is extracted from the northern leopard frog, Rana pipiens.
Ranpirnase belongs to a class of enzymes called ribonucleases. Ribonucleases are enzymes that break down RNA, a large biomolecule that plays an important role in decoding DNA and making proteins that keep cells growing and dividing.[2]
How Does Onconase Work?
As a ribonuclease, Onconase degrades or breaks down RNA molecules in cells.[2] Exactly how it might do this in cancer cells is not fully understood, but there are several ways it might disrupt the growth and division of these cells.
Onconase causes more damage to cancer cells than healthy cells, making it more selective than other chemotherapy drugs. Why it selects cancer over healthy cells is not understood, but one possible idea is that cancer cells carry a negative charge that attracts the therapeutic enzyme.[3]
Has Onconase Received FDA Approval?
The FDA has not approved this drug but has granted it orphan drug status.[4] An orphan drug is developed to treat a rare disease.
The FDA uses orphan drug status to encourage pharmaceutical companies and researchers to advance treatments for diseases that affect fewer than 200,000 people each year. Mesothelioma is one such disease.
The FDA removed the orphan drug status for ranpirnase in 2009. However, OrGenesis reported in 2021 that it had consulted successfully with the FDA on the use of it as a topical gel for general warts.
The company plans to continue testing Onconase for a variety of infections in clinical trials, including COVID-19.[5]
Onconase and Mesothelioma in Clinical Trials
Several Onconase clinical trials in mesothelioma patients have begun or been completed. Some have progressed as far as phase III.
One phase II trial involved eighty-one patients with mesothelioma. Ranpirnase was used as a single-agent drug in the trial. Forty-one patients had a stable disease response or better, which was enough to advance to phase III.[2]
Early results from the phase II trial showed promise for ranpirnase in treating mesothelioma. For one phase III trial, patients received either doxorubicin or ranpirnase. Those who received ranpirnase seemed to have longer survival times, though the results were unclear due to the study design.
Another Onconase trial for mesothelioma found that a combination of doxorubicin with ranpirnase was more effective than using either medication alone. Unfortunately, by the end of this trial, the patients in the doxorubicin-only group lived longer than in previous trials, so there was no statistical improvement between treatments.
It seems that ranpirnase stabilizes tumors more than reduces them, demonstrating that this drug could be good in combination with others for managing mesothelioma and extending survival times.[2]
Another clinical trial of ranpirnase recruited non-small cell lung cancer patients beginning in 2010. The researchers combined it with pemetrexed and carboplatin chemotherapy. Unfortunately, the study was withdrawn in 2015, and no results were posted.[6]
Side Effects of Ranpirnase
Chemotherapy is often effective in treating cancer, but it causes significant side effects for many patients. Onconase may be helpful for mesothelioma patients because it is given in lower doses than other chemotherapy drugs.
With these lower doses, Onconase may cause fewer side effects than chemotherapy drugs. Clinical trial results found that kidney toxicity was the main limiting factor in dosing and that there were few adverse events or side effects seen in participating patients.
Onconase Combined with Malaria Drugs to Treat Mesothelioma
While the clinical trials with Onconase treating mesothelioma have shown some promise, researchers have concluded that the results are mixed and that more work is needed to determine if this drug is helpful to patients.
Late phase III trials failed to prove that Onconase alone was more effective than other chemotherapy drugs. Research into using this agent for cancer has stalled.
This roadblock has also led to more creative uses of Onconase, including combining the drug with another used to treat malaria. Scientists at Tongji University in China conducted the research. It included mixing Onconase and dihydroartemisinin (DHA).
The researchers used this combination to combat mesothelioma cells in a laboratory setting and mice. They found the DHA enhanced the anti-cancer effect of Onconase in both situations.[4]
DHA is an antimalarial drug but has also been shown to affect and suppress tumor growth. It may also prevent the growth of blood vessels that supply tumors. Whether the work conducted with ranpirnase and DHA will progress into clinical trials with human patients remains to be seen.
Onconase’s future is uncertain. While clinical trials have slowed down, some researchers continue to study the compound and may find the right combination of drugs to help mesothelioma patients live longer and more comfortably. Even unorthodox combinations, like ranpirnase with a malaria drug, could eventually lead to new treatments.
