New FDA Approval: Mvasi
The treatment of specific cancers:
- Colorectal cancer: metastatic, w/ IV 5-FU for 1st/2nd line treatment or w/ fluoropyrimidine-irinotecan- or fluoropyrimidine-oxaliplatin-based for 2nd line in patients who progressed on first-line bevacizumab containing regimen, not for adjuvant therapy in surgically resected colorectal cancer
- Lung cancer: non-squamous non-small cell, w/ carboplatin and paclitaxel as 1st line of unresectable, locally advanced, recurrent or metastatic
- Brain: glioblastoma w/ progressive disease following prior therapy, based on improvement in objective response rate (no data available showing improvement or survival with bevacizumab products)
- Kidney: metastatic renal cell carcinoma, w/ interferon alfa
- Cervical: persistent, recurrent, or metastatic, w/ paclitaxel and cisplatin or topotecan
Let's also note that the old bevacizumab [Avastin] has indications on its package insert for ovarian, fallopian tube, and peritoneal cancers. Tiny doses of Avastin (usually 3 mg) are also used off label as a treatment for macular degeneration of the eye. It stands to reason that Mvasi will eventually end up in these areas too.
I'm also having fun coming up with new slang terms for the old bevacizumab. Should we call it "regular" bevacizumab? Unleaded? Basic? I think I'd like to see a trend where we call all drugs that end up with biosimilars "basic."
How it Works
Is it pronounced like embassy, but with a v? Emvahhhsee? Or do you insert a vowel sound between the 'm' and 'v'? Mahvahsee? Is the 'm' silent? Vahsee? Or the 'v'? Mahsee?
Whatever it is, #yabda (yet another biosimilar drug approval). We're going to make this a thing. Like 'fetch'.
If you recall our previous posts about biosimilars (here, here, and kinda here), biologic drugs are made in organisms, which can lead to variability in the product. If you use a different organism (or a different environment) to create the drug, you can get a different product. A commonly touted maxim in the biologic world is "The process is the patent."
So, since each biologic drug is its own little snowflake, Mvasi is basically Avastin...but it's technically different. Thanks to the FDA biosimilar program, it can have the same indications as Avastin, but it hasn't yet been exposed to the number of patients it will see once its use starts ramping up (so its treatment effect and side effect profile will need careful scrutiny).
However, just like regular generics, the expected activity is the same, and accordingly the side effects too.
So how does Mvasi work? By inhibiting a factor called Vascular Endothelial Growth Factor (VEGF). VEGF is a signaling molecule that leads to new blood vessel formation. Cancer cells divide rapidly, and need a lot of fuel (oxygen) and waste disposal to keep those costly processes up. So they effectively build an infrastructure of roadways and supply ships complete with a waste management crew. VEGF is sort of like the construction foreman, organizing and stimulating the growth of these new blood vessels to supply the tumor cell.
VEGF inhibitors like Mvasi are monoclonal antibodies directed against VEGF. They bind to it, and stop it from binding to its receptor (thus shutting down new blood vessel growth).
Notable Adverse Effects
So Mvasi has a few notable places in therapy. How's it tolerated?
Well...relative to some of the classic cytotoxic chemotherapy like cisplatin and paclitaxel, Mvasi isn't so bad. But don't let that get you too excited. There's a heck of a lot of bad things associated with Mvasi too.
Imagine the end of a Cymbalta or a Jardiance commercial (like you see when watching "So You Think You Can Dance" on Hulu). You know how they whiz through a super long list of adverse effects at lightning speed?
It's like that (but probably worse) for Mvasi.
To be fair, before giving you this information, please know that some of the reported adverse effects were from studies with bevacizumab alone, and some were reported when given in combination with chemotherapy. So the true incidence might be a little more difficult to pin down.
Epistaxis (as high as 55%), headache (up to 49%), hypertension (19 - 42%), rhinitis (17%), proteinuria (as high as 36%, and lasting about 6 months before resolution), altered taste (14 - 21%), dry skin (7%), hemorrhage (40%), back pain (21%) and exfoliative dermatitis (23%). By the way, these are the "common" effects, not "serious" effects.
Basically, you'll be a teary eyed, flaky skin, back and head hurting, peeing protein, irritated nose that keeps bleeding (not to mention anus), can't taste your food, high-blood-pressure mess. But at least the cancer might be slowly going away?
But, that's not all!
Mvasi also has some pretty serious side effects. Stuff like:
- Perforation or fistulas
- Arterial and venous thromboembolic events
- Hypertension (again)
- Posterior Reversible Encephalopathy Syndrome (PRES)
- Proteinuria (again)
- Infusion-related reactions
- Ovarian failure
These side effects are in line with other VEGF inhibitors. Really, they're in line with anything that inhibits blood vessel growth. So they're not necessarily unexpected (even if they do seem pretty severe).
There are also different grades to some of these side effects. Grade 3 and 4 are more severe than Grade 1 and 2. Of course, the package insert does warn that treatment should be stopped if the side effects are severe or life threatening. But then again there aren't too many degrees of "tolerability" to blood clots, holes in your organs, peeing lots of protein, super high blood pressure, a swelling brain, infusion reactions and no more babies. Oh, and pregnant people? Watch out, this stuff will harm your fetus.
One more thing. If you didn't already know, Avastin has a black box warning for gastrointestinal perforations, delayed wound healing, and severe bleeding of basically anything that can bleed. Those all extend to Mvasi.
Of particular note is the 28 day hold time before and after elective surgery:
"Patients should stop using Mvasi if gastrointestinal perforation occurs. Patients should not take Mvasi in the 28 days prior to and after elective surgery, and until the surgical wound is fully healed. Patients should stop using Mvasi if a surgical incision breaks open (wound dehiscence). Mvasi should not be given to patients with severe hemorrhage or in patients who cough up blood (hemoptysis)."
Current Place in Therapy
Biosimilars are fairly easy to add to your brain, since most of the stuff is a "me-too" type of add (since you already have extensive knowledge about the original).
In terms of place in therapy, right now Mvasi (and other biosimilars) are generally indicated for the same things as the original drug, and have basically the same side effects and toxicities.
Just like when a drug goes generic, biosimilars offer a lower cost alternative (theoretically) to the original, which should help improve access. Unlike generics, however, we don't have a ton of experience with biosimilars. It's a new realm for us, as the concept of biologic (and biosimilar) drugs is so new.
I would expect that Mvasi will be added to (if not become the preferred agent) on most formularies as it becomes available. We'll also likely see other biosimilars for bevacizumab coming to market (similar to how we now have Renflexis and Inflectra as biosimilars for Remicade).
All that being said, it's not yet clear how Amgen plans on pricing Mvasi. It may take additional competition (via a second biosimilar for bevacizumab) before we notice a truly significant cost decrease.
All in all, this is another #yabda (seriously, we're going to make this a thing) and it's likely we're going to see many more to come.