Onconase (Ranpirnase)

Onconase, also known as ranpirnase, is an example of a novel type of medication being tested for treatment of a variety of cancers, including mesothelioma. It is not yet approved by the U.S. Food and Drug Administration (FDA) for any use, but it is being tested in clinical trials and is showing promising results in managing difficult cancers like mesothelioma and extending patient’s lives.

This drug is different from other chemotherapy drugs in that it is an enzyme and is thought to stabilize cancer cells and prevents tumor growth. In this way it may be more of a management tool in cancer than a hope for a cure, but it shows potential for helping patients live longer. It also may cause fewer side effects than traditional chemotherapy drugs.

What is Onconase?

Onconase is the brand name of a drug currently made by TamirBio. The company focuses on developing antiviral drugs, and Onconase is already being shown to be effective in treating the human papilloma virus, HPV. Although it already has a brand name, and the generic name ranpirnase, Onconase is not yet approved in the U.S. for treatment of any disease. This may change soon as more clinical trials show that it can be safe and effective.

Ranpirnase is an enzyme, a large protein that helps biological reactions go forward, speeding them up or just helping them get started. It is a natural enzyme that was 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 does that in cancer cells is not fully understood, but there are several possibilities for where it may play a role in interrupting the growth and division of these cells. It has also been proven that Onconase is causes more damage to cancer cells than healthy cells, which means that it is more selective than other chemotherapy drugs. Why it selects cancer over healthy cells is not known, but one idea is that cancer cells carry a negative charge and this may be what attracts the therapeutic enzyme.

Onconase and Mesothelioma

The FDA has not approved this drug, but it did give it orphan drug status in 2007. An orphan drug is a drug that is developed to treat a rare disease. The FDA designates drugs this way to encourage pharmaceutical companies and academic researchers to advance treatments for diseases that affect fewer than 200,000 people each year. Mesothelioma is one such disease and with the promise it has showed as a treatment, Onconase received the orphan drug status from the FDA.

Several clinical trials with mesothelioma patients have begun as a result of the orphan drug status given to Onconase, and some have progressed as far as phase III trials. One of the largest of these trials was a phase II trial that involved 81 patients with mesothelioma. Ranpirnase was used as a single agent drug in the trial. Forty-one of the patients saw decreased tumor progression, and this was enough to advance onto a phase III trial.

Early results from that trial continued to show promise for ranpirnase in treating mesothelioma. Patients were given either doxorubicin or ranpirnase. Those who received ranpirnase had longer survival times. Another Onconase trial with mesothelioma patients found that a combination of doxorubicin with ranpirnase was even more effective than using either chemotherapy drug alone. An important conclusion from many of these trials is that ranpirnase seems to stabilize tumors more than reduce them, demonstrating that this drug could be a good drug for managing mesothelioma and extending survival times.

Side Effects

One of the reasons that Onconase may be helpful for mesothelioma patients is that it takes lower doses to see an effect on the tumor as compared to other chemotherapy drugs. Chemotherapy is often effective in treating cancer, but it also causes terrible side effects for most patients. With 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 and mesothelioma patients have shown great promise, researchers have concluded that the results are mixed and that more work is needed to determine if this drug really helps patients. In fact, late phase III trials failed to prove that Onconase alone was any more effective than other chemotherapy drugs. While this halted some research in the U.S., Onconase continues to be tested as an orphan drug for mesothelioma in Europe and Australia.

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 that combination to combat mesothelioma cells in a laboratory setting and in mice. The DHA was found to enhance the anti-cancer effect of the Onconase in both situations.

DHA is an antimalarial drug, but has also been shown to have effects on tumors, including suppressing the growth of tumors. It may also be able to prevent the growth of blood vessels that supply tumors with blood and nutrients. Whether the work conducted with ranpirnase and DHA will progress to clinical trials with human patients remains to be seen.

Where the research will continue with Onconase remains to be seen. While clinical trials in the U.S. have slowed down, those in other parts of the world are continuing 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 may be an option that is eventually developed into a real treatment for patients who need it.