All About Vyxeos

What is vixios? Vixios is kind of an interesting drug. It's a it's a combination of two drugs actually that are commonly used for induction therapy in AML and those two drugs are donor rubicon and citarabene and vixios is a liposomaal liposomally encapsulated formulation of those two drugs in a fixed molar concentration ratio that is shown to be synergistic. So what you get with Vixio is the two drugs Donna Rubicon and Caiterine delivered together within a liposome directly to the cancer cell at the appropriate synergistic ratio that makes them work ideally together and gives them a better chance of killing the cells together than each individual drug by itself. How is Vixio different than 7 plus 3? Vixios is a liposomally encapsulated formulation of 7 plus3. So it encapsulates both donor rubicon and citarabine in a fixed concentration ratio that allows for the uh for the drugs to be delivered together to the cancer cell to optimize cell killing. So they're the same drugs but given in a different formulation that's more um advantageous when it comes to drug delivery. How is Vixio administered? Aixios is administered um as an IV infusion given typically as a single daily dose on days 1, three and five. So a total of three doses uh for each each round or each induction regimen. Um in consolidation it's typically given as a twod dose schedule. So Vixio is typically administered as an introvenous infusion um on day one, day three and day five. So three doses each dose about 48 hours apart. Um it can be given as an inpatient or in the outpatient setting as well. Many centers are now transitioning more to outpatient based induction with regimens that are easy to administer like Vixio that don't take very long provided that there's enough support to allow patients to be seen quickly or come back in quickly if they get sick. Um but um it can be done either as an inpatient based therapy or an outpatient based therapy. And at our center we we do some of both depending on the patient's particular situation. The dosing of Vixios is typically 100 units per meter squared on days 1, three and five as induction therapy. Um the dose is not usually modified during induction. Um but it is modified downward during subsequent post-remission cycles. Consolidation therapy in other words where we don't want to cause as much or as severe or prolonged periods of cytoenas. So the dose is typically reduced during consolidation and given on days one and three only instead of days 1, three, and five. What is secondary AML? Secondary AML is a term that's used to refer primarily to AML that arises uh from something else. Most often uh the most common setting of secondary AML is AML that arises from prior myoisplastic syndrome. So that's what we often see in cases of secondary AML. Secondary AML can also be considered treatment related AML in some cases where the AML emerges following prior chemotherapy and or radiation therapy for a second cancer. It can also arise or it can also be considered secondary AML if it arises from a prior myo proliferative neoplasm. Now, that's not quite as common as uh when it arises out of MDS or um following therapy for other cancers. So, those are all the subtypes of secondary AML. But the term secondary AML is becoming a little bit outdated as we learn more about the molecular features of AML. And many of the uh features of secondary AML are are are more related to specific genetic abnormalities that are often seen in MDS or myop proliferative neoplasms or in the case of therapy related AML TP53 mutations. What is the difference between secondary AML and therapy related AML? Well, therapy related AML is considered a type of secondary AML. um within the context of other secondary AML subtypes as well such as secondary AML that comes from MDS or from myop proliferative neoplasm. So therapy related AML has traditionally been considered a type of secondary AML. How are outcomes different for people with primary AML versus secondary AML? Yeah, traditionally secondary AML is associated with worse outcomes than primary or denovo AML. And that's probably because mostly of the abnormal or adverse genetic features associated with secondary AML, not necessarily just secondary AML by itself. So secondary AML as I mentioned before is sort of this uh conglomerate term for many different types of AML that arise in different settings that often were associated with MDS or myo proliferative neoplasms and we know that secondary AML traditionally does more poorly than denovo AML but that's not always the case it depends on uh primarily the genetic features of the disease and the prior treatment history of the patient as Well, so patients that have received prior therapy for say myodisplastic syndrome with drugs like aocytoine or decittoine clearly have worse outcomes once they develop AML because the drugs for AML just don't work as well once a person has already been treated for for MDS which includes many of the same drugs that we actually use for AML. How effective is Vixio for people with secondary AML? So that is secondary AML is the primary indication for Pixio and that's the basis that was the basis for its approval by the FDA back in 2017. It um it's effective and it induces remission in approximately 50% of patients uh that receive it as induction therapy. and it is associated with a longer survival than patients who receive induction chemotherapy with 7 plus three. Um we found in a phase three study that Vixios was able to bridge about onethird of all patients to a transplant and that the outcomes after transplant in patients who had received Vixios as primary induction therapy um were better. So that it seems that for some reason that we're not totally clear about that transplant outcomes are better if patients got Vixios as their initial therapy than if they had gotten 7 plus 3. What are the common side effects of Vixio and how are these side effects managed? So the side effects that you see with Vixio are very similar to what you see with really any type of induction chemotherapy for AML. uh the main side effects are related to lowering of blood counts. So patients are more susceptible to infections and the manifestations of infections like fevers and chills and and other signs and symptoms of infection. You can see serious infections uh with Vixio treatment that is related to the suppression of the blood counts and the risk for uh different types of infections especially fungal or mold infections when the white blood cells are very low. But that's not unique to Vixio. uh it's common with commonly seen with with many different types of induction chemotherapy. I think with Vixio the the one perhaps outlying side effect is that there tends to be a more delayed time to recovery of of white blood cell counts and platelet counts in particular that probably reflects that the fact that the Vixio um is in the circulation for longer. It doesn't get broken down as quickly. So um the the overall exposure to the drug is longer and therefore that the blood count recovery takes longer but at the same time we think that it works better in in secondary AML uh compared to 7 plus 3. So um the trade-off is a little bit more of a delay in count recovery um for improved efficacy. Convixios cure AML. Well, that's a hard question to answer. We think in most cases the patients that are treated with Vixios that have secondary AML are not dealing with a subtype of AML that is considered curable without a bone marrow transplant. Now there may be some cases where Vixios does cure patients but that's clearly not the the majority of patients and the path to cure for most cases of AML especially secondary or higher risk AML subtypes is clearly through a bone marrow transplant. Pixios is effective at getting patients into remission and paving the way for a future bone marrow transplant that can be curative and that's I think its main role is to get excellent disease control and bridge the patient to a potentially curative transplant. What research is being done with Vixio to make this therapy more effective? So there's a lot of uh different clinical research studies being done right now to um better understand how Vixios might be used in combination with other newer and targeted drugs. Right now there are several trials going on that are combining Vixios with with drugs such as venetlax uh drugs such uh such as guiltitanib which is a flit 3 inhibitor uh drugs such as gemttomab which is a which is a cd33 antibbody drug conjugate. So there's quite a bit of excitement that Vixio can be a platform uh with which to combine other targeted therapies to further improve the outcomes but we definitely need to see more in the way of mature studies to really understand the impact of these combinations. So there has been a lot of progress made in the therapy for AML over the past five to seven years including not just Vixios but several other novel therapies in combination. And I think the most notable one that has really become mainstream in the clinic is the combination of aocyitine and venettolax. And that regimen was developed primarily for older, less fit, more frail patients and determined to have a a really impressively high response rate and survival rate uh in that group of patients. It kind of led to the question, well, if it works very very well in this less fit group of patients, wouldn't it work just as well or maybe even better in in younger, more fit patients? And that may be true. Um, and then the next question would be, well, how does it compare to more traditional therapy or more intensive therapy such as Vixio? And unfortunately we don't have an answer to that question because the two regimens bixio on one hand and aocitine benettolex on the other hand have never been compared head-to-head. So without a randomized trial it's very difficult to make assumptions as to which treatment may be better or are they the same and what are the implications for toxicity hospitalizations future transplant. uh we just don't know the answer to those questions. Uh what we can say is that Vixios is better than 7 plus 3 in the secondary AML setting and should be preferred should be the preferred regimen over 7 plus 3. I think when it comes to deciding on Vixio versus A ascitedine plus venettolex that's a very in-depth personalized discussion between the the health care team and the patient because there may be reasons for doing one versus the other that are not necessarily related to the disease but may be related to other factors such as the physical status of the patient their ability to travel back and forth to the clinic on a regular frequent basis for transfusions as an outpatient if if they're not dealing with a good support system at home. So, there are many factors that go into that decision and hopefully we'll have models that are developed over the next uh few years that help us make that decision more rationally and and based upon evidence rather than just um you know the physician or the physician's team objective or subjectively deciding what might be best for the patient.