The last two years or so have been very successful for Hepatitis C treatments. The revolutionary new line of drugs that was registered for chronic Hepatitis C since 2013 feature over 90% cure rates and a pill-per-day regimens. Asunaprevir is the latest drug that could provide an edge especially in patients who are difficult to treat. With a completely new mechanism of action, asunaprevir (the drug is already registered in Japan under the trademark name Sunvepra) might be very useful for the following patients:
- Asunaprevir could benefit patients who didn't respond to prior therapy with Sovaldi, Harvoni, Daklinza, Zepatier and so on
- Asunaprevir could also benefit who were medically ineligible or intolerant to previous treatment
Asunaprevir, produced by Bristol-Meyers Squibb, has recently undergone clinical studies and is currently used (limited countries) under its trademark name Sunvepra with Daklinza (daclatasvir). Different regimens with interferon and ribavirin are being tested, as well as interferon-free and ribavirin-free regimen. In a mid-stage study, a 24-week regimen with asunaprevir and daclatasvir was used for the treatment of difficult-to-treat patients and achieved a promising 77% cure rate.
How does Asunaprevir treat Hepatitis C?
We already have several drug molecules for the treatment of Hepatitis C that as asunaprevir are very effective at fighting Genotype 1 cases. These include sofosbuvir, ledipasvir, daclatasvir, ribavirin and so on. One important difference between asunaprevir and these drugs is the novel mechanism of action asunaprevir brings to the table.
For example, the most well-known Hepatitis C drug sofosbuvir works by inhibiting NS5B protein in Hepatitis C virus. Sofosbuvir is not used for treatment by its own; modern treatments fight Hepatitis C virus with 2 or more drug molecules. Harvoni, for instance, includes ledipasvir, an NS5A protein inhibitor, to more effectively fight HCV, and even the most basic Sovaldi (400mg sofosbuvir) regimen includes ribavirin or/and interferon.
Safe to say, it is important to have as many as possible drugs working in different ways to most effectively treat Hepatitis C, and asunaprevir is another useful way how to target HCV. What is important to understand is that viruses are a living matter (albeit scientist disagree if viruses are actually alive or not; they do agree on that they are able to change and adapt to the environment). If you have ever wondered why we have 6 genotypes of Hepatitis C virus, here is your answer – it is this adaptational ability that enables HCV to change and fight against the drugs that are used to fight it.
The solution: Hit HCV with everything we got at the same time. Hepatitis C treatment consists of two or more drugs to attack two or more targets in the virus. Asunaprevir offers us a new way to target the virus that proved to be very resilient to existing drugs.
Asunaprevir Mechanism of Action
Asunaprevir (formerly known as BMS-650032) works unlike any other Hepatitis C on the market. The mechanism of action of asunaprevir is to target a specific HCV enzyme called serine protease NS3. This is an enzyme that virus needs for normal functionality and replication, and by blocking it, asunaprevir inhibits HCV ability to grow while immune system swoops in with antibodies to fight off the remaining virus.
Asunaprevir's molecular structure
Sunvepra (100mg asunaprevir) is often partnered up with Daklinza (daclatasvir) for treatment. In such a way, daclatasvir can target NS5A protein while at the same time asunaprevir targets NS3. The virus can try to fight each of the drugs by changing its morphology, pumping out the drug, and so on, but if for example it can resist the attack of daclatasvir on NS5A protein, asunaprevir can still finish it off by attacking NS3 protein and impede HCV's ability to replicate.
Asunaprevir in Japan
Sunvepra which consists of 100mg of asunaprevir is currently not registered as widely as other Hepatitis C drugs. The treatment is used primarily in Japan and Russia.
In an official statement by Bristol-Meyers Squibb about asunaprevir, the chief scientist working on the project, Kazuaki Chayama of Hiroshima University in Japan, explain why asunaprevir was specifically registered in Japan.
“Japan has a unique hepatitis C patient population, many of whom are older and have been unable to take, or respond to, traditional therapies, so we have a real sense of urgency to treat these patients now."
Nonetheless, some speculation about BMS's move to limit the countries in which they registered Sunvepra point out that it may have something to do with limited competition in Japan and Russia, and the problem of lower effectiveness of asunaprevir regimen compared to other Hepatitis C treatments.
When HCV becomes more and more resistant…
In the case of viral infections such as Hepatitis C, an arsenal of many different drugs can prove very useful in the long term. Viruses such as HCV have outstanding survival mechanisms which can even render a drug that was once had 100% cure rate ineffective. By broadening the number of molecules we have to fight HCV, we are reducing the risk of HCV resistance to drugs. For example, if HCV learns how to render sofosbuvir inactive, we have daclatasvir, ledipasvir, ribavirin and now asunaprevir to continue the fight.
