Onconase (Ranpirnase)

Onconase^®, also known as ranpirnase, is a novel agent being tested for a variety of diseases, including mesothelioma. It is not yet approved by the U.S. Food and Drug Administration (FDA) for any use, but it could one day have positive impact upon patients with mesothelioma.

Onconase is different from other chemotherapy agents. It is an enzyme thought to stabilize cancer cells and prevent tumor growth, which may make it more of a management tool in cancer than a cure, but it could possibly help keep patients alive longer. It also may lead to fewer side effects than traditional chemotherapy drugs.

What is Onconase?

Onconase is the brand name of ranpirnase, a medication manuactured by TamirBio. This company develops antiviral drugs, and Onconase has already shown promise in treating the human papilloma virus, HPV. Although ranpirnase already has a brand name, Onconase is not yet approved in the U.S. for treatment of any disease. This may change as more clinical trials show it can be safe and effective in other diseases.

Ranpirnase is an enzyme, a large protein that helps modify biological reactions, speeding them up or just helping them get started. Occuring in nature, 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.

How it Works

As a ribonuclease, Onconase degrades or breaks down RNA molecules in cells. 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.

Onconase and Mesothelioma

The FDA has not approved this drug, but did grant it orphan drug status in 2007. 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. Unfortunately, the FDA removed the orphan drug status for this drug in 2009.

Several Onconase clinical trials in mesothelioma patients have begun, and some have progressed as far as phase III. One phase II trial involved 81 patients with mesothelioma. Ranpirnase was used as a single agent drug in the trial. Forty-one of the patients had a response of stable disease or better, and this was enough to advance to phase III.

Early results from the phase II trial showed promise for ranpirnase in treating mesothelioma. For one phase III, patients were given either doxorubicin or ranpirnase. Those who received ranpirnase seemed to have longer survival times, though the results were unclear due to study design. Another Onconase trial in 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 that there was no statistical improvement between treatments. It seems that ranpirnase works to stabilize tumors more than reduce them, demonstrating that this drug could be a good drug in combination with others for managing mesothelioma and extending survival times.

Side Effects

Onconase may be helpful for mesothelioma patients because it is given in lower doses compared to other chemotherapy drugs. Chemotherapy is often effective in treating cancer, but it causes significant side effects for many patients. With these lower doses, Onconase may cause fewer side effects. 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 with Malaria Drugs

While the clinical trials with Onconase in 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 actually helpful to patients. Late phase III trials failed to prove that Onconase alone was any more effective than other chemotherapy drugs. Research in this agent has now slowed across much of the world.

This roadblock has also led to more creative uses of Onconase, including a combination of the drug with another used to treat malaria. The research was done by scientists at Tongji University in China and included mixing together Onconase and dihydroartemisinin (DHA). The researchers used this combination to combat mesothelioma cells in a laboratory setting and in mice. The DHA was found to enhance the anti-cancer effect of Onconase in both situations.

DHA is an antimalarial drug, but has also been shown to have effects on tumors, including suppressing their 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 are continuing to study the compound and may find the right combination of drugs that will help mesothelioma patients live longer and live more comfortably. Even unorthodox combinations, like ranpirnase with a malaria drug could eventually lead to new treatments.

Page Medically Reviewed and Edited by Kyle J. Becker, PharmD, MBA, BCOP

Kyle J. Becker, PharmD is certified by the Board of Pharmacy Specialties in Oncology Pharmacy. Dr. Becker earned his pharmacy degree from Shenandoah University and he currently serves as an oncology pharmacist at Parkview Cancer Institute.

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