New Treatment on the Horizon: AVX-470

Avaxia Biologics, Inc., a clinical-stage biopharmaceutical company developing gut-targeted therapeutics, announced today that primary and secondary objectives were successfully met in a first-in-human Phase 1b clinical trial of AVX-470, an oral anti-TNF bovine polyclonal antibody, in patients with active ulcerative colitis.

The primary objective of the trial was to evaluate the safety and tolerability of AVX-470. No treatment-related serious adverse events (SAEs) were observed, and there were no allergic reactions or opportunistic infections.

The secondary objectives of the trial were to evaluate the pharmacokinetics and immunogenicity of AVX-470. Pharmacokinetics were assessed by measuring bovine immunoglobulin levels in serum, stool and colon tissues. Immunogenicity was assessed by measuring whether AVX-470 induced a human anti-bovine immunoglobulin antibody (HABA) response in serum. Serum concentrations of bovine immunoglobulin remained within the range of baseline values established in patients before dosing with AVX-470, supporting the hypothesis that AVX-470 acts locally in the gut. As expected, many patients had low concentrations of bovine immunoglobulin in serum at baseline, presumably from dietary exposure. Bovine immunoglobulin was detected in colon tissue, confirming that the antibody can penetrate into the colon tissue in ulcerative colitis patients. Bovine immunoglobulin was also detected in stool and had the ability to bind TNF, confirming that AVX-470 resists digestion in the gut. Finally, treatment with AVX-470 did not cause an increase in HABA in serum, supporting the hypothesis that the antibody will display minimal immunogenicity.

The trial also included as exploratory objectives the evaluation of clinical and endoscopic responses and effects on biomarkers. AVX-470 showed consistent trends across multiple clinically important endpoints and reduced serum C reactive protein (CRP) and tissue TNF levels at the highest dose. These efficacy trends are highly encouraging because they were reached with a small number of patients after only four weeks of dosing, as compared to the eight weeks of dosing typically required to see significant effects with ulcerative colitis treatments.

“Results from our first clinical trial with AVX-470 exceeded our expectations. AVX-470 was well tolerated with no safety signals observed, exhibited the pharmacokinetic properties needed for a gut-targeted antibody therapeutic, and did not induce an anti-drug antibody response. In addition, AVX-470 showed consistent efficacy trends for clinical response, clinical remission, and both pharmacodynamic and disease-associated biomarkers,” said Barbara S. Fox, Chief Executive Officer of Avaxia. “With such positive results, we plan to advance AVX-470 into Phase 2 development.”

The Phase 1b trial was a double-blind, placebo-controlled, ascending dose study of AVX-470 in active ulcerative colitis patients. This was the first human study of AVX-470. Three different dose levels of AVX-470 were administered for a period of 28 days. The study involved 14 trial centers in the U.S., Canada, Belgium and Hungary. A total of 36 patients were treated in the trial, with nine patients receiving placebo and 27 patients receiving the drug. The trial was completed in December 2013.

Avaxia plans to disclose detailed study results at upcoming scientific meetings or in a peer-reviewed publication.

about AVX-470

AVX-470 is the first gut-targeted anti-TNF antibody in clinical development. The lead indication is inflammatory bowel disease (IBD). Currently marketed anti-TNF drugs are highly effective for the treatment of IBD. However, despite their success, these drugs have two significant drawbacks. One is that they must be injected, whereas patients prefer oral medications. More importantly, they cause rare but serious side effects, such as risk of serious infection, because they dampen the immune system throughout the body, not just in the intestines where the disease occurs. As a result, these drugs are used mostly as a second- or third-line therapy, despite evidence that earlier use may improve patient outcomes. In contrast, AVX-470 is an orally administered antibody therapeutic that targets the gut, potentially improving safety and efficacy over existing anti-TNF therapies. Avaxia believes that AVX-470 has the potential to become a first-line therapy that transforms the treatment of IBD.

about Avaxia Biologics

Avaxia is a leader in the growing field of gut-targeted therapeutics — orally administered, minimally absorbed drugs that are designed to act locally in the gastrointestinal tract. Avaxia’s lead clinical candidate, AVX-470, is an oral anti-TNF antibody for inflammatory bowel disease. AVX-470 offers potentially improved safety and efficacy over existing anti-TNF therapies by focusing immune suppression only where needed in the diseased gut. Avaxia plans to use its gut-targeted antibody platform to develop therapeutics to address many other serious diseases such as celiac disease, metabolic disease and GI acute radiation syndrome. www.avaxiabiologics.com.

So if it is in phase 1 then how many years does it take to hit the market?

I mentioned this one before on here. When I went for a surgical consult last year, a locum GI dissuaded me and told me to try this therapy, as I was close by to the centre that offered it. I received the drug information, got in touch with the coordinator and was close to enrolling. I have the big ass packet detailing how it works if anyone wants it.

What I like about it:
- it's colostrum, so it contains many antibodies, immune factors, peptides that stimulate gut healing.
- it is from cows injected with human antiTNF blood, so it theoretically it should produce a more amplified response than just regular colostrum alone.

What I hate about it:
- They gave me zero info on whether the cows were grassfed and pastured. They averted this when I pressed and just said everything was USDA approved. That means absolutely nothing. This was a major red flag for me. The cows are obviously factory farmed.
- It just targets one out of many possible inflammatory mechanisms (TNF) and doesn't address other components - microbiome, nutrition, etc. Raw colostrum by itself is very nutritious and filled with beneficial microbes. This is pasteurized and then freeze dried colostrum from my understanding.

I ended up backing out because too many things were shady for me and they did not give me all the information I needed. I do think this is one of the safer therapies out there and could potentially be used as a first line one if the results are good.

Aguywithuc do you take colostrum?

This looks interesting, but I cant for the life of me figure out why they used a cow as their animal model of choice. First of all it is a very difficult animal to use for any lab work. Secondly, and most importantly, it will give us, AT BEST, humanized antibodies, so there is still the chance of developing antibodies to the antibodies. The technology is out there to make fully human antibodies (see Xenomouse), but there are very few new antibody treatments that use it. Oh well, I guess I dont really care as long as the thing works. Heres to hoping!

Thanks Indy for the info re length of phases till market approval. P.s. I like your 2014 plan: kinda similar to my own plan.

i've been taking colostrum and lactoferrin pills for a while now. i think i started back in 2012 when i was very sick. didn't help at the time but i still take them anyway. i get grass fed ones, obviously, because the growth hormones and antibiotics in the factory farmed cows aren't going near my body. it is sketchy that they wouldn't disclose where the cows are from. whatever goes into their bodies will go into their milk supply and into our bodies if we chose to take this pill every day.

granted, i didn't research where my imuran or simponi is coming from just because i was desperate for something to work. if these end up failing me, i would try this if it gets approved and the trials go well.

I take colostrum also, and only by NZ colostrum.. I take it more for preventative measures... The studies I've read says it increases gut permeability.. Def gave me a die off reaction when I first started it.. So must kill something

LOL. It is colostrum, guy, albeit rhTNF hyper-immune colostrum. Hyperimmune colostrum has been around since the day of stolle milk and they've popularized it in China. There's also a guy named Jerry Brunetti who did this back in 1999 and used it to treat non-Hodgkin’s Lymphoma. You need to do your research.

Straight from the packet:

AVX-470 is extracted from the early milk (colostrum) of pregnant dairy cows that have been vaccinated with a substance called recombinant human tumor necrosis factor (rhTNF). Colostrum is rich in antibodiesl and people often ingest large amounts of these antibodies each dayr by drinking cow`s milk. The process of vaccinating pregnant dairy cows with rhTNF leads to
the production of antibodies against TNF in the Colostrum. The colostrum is collected and purified and Consists largely of antibodies that are found in milk. including the antibodies made against TNF. Nalurally-occuriing cows milk antibodies (not specifically raised against a human
protein like TNF) are recognized as safe by the FDA at amounts almost ten times higher than what you will use in this study.. The addition of antibodies against TNF to these milk antibodies is what makes AVX-470 experimental."

They mention that it could cause a reaction to those with milk protein allergies at the end and has lactose content in it, so it might not be suitable for some people. Extracting modulated colostrum from colostrum still makes it colostrum. The distinction is clear, but the definitions don't change.

Say what again? This is straight form the experimental packet I received from the manufacturer when I was close to enrolling. I'll give you the number of the coordinator. I also have the number of the PR agent who works @ AVX to confirm it is colostrum.

And humans do produce IgG in their milk but in very trace concentrations.

You can call me Guardian now thank you very much.

Post Edited (Guardian7) : 5/3/2014 3:47:12 AM (GMT-6)

Which is why they, again, mention that it might not be suitable for those with dairy allergies. It has all the same components that colostrum has - casein, lactose, minor whey. Refined colostrum still makes it colostrum.

Call them to confirm that it is colostrum by definition.

You have not done your research.

Post Edited (Guardian7) : 5/3/2014 3:51:44 AM (GMT-6)

I'm actually curious if you've taken any courses in simple logic or computer science. Polymorphism is taught in grade-school computer science and it allows us create a new entity by extending the properties of an existing entity. Regardless, when polymorphism principles are used and a new entity is created, that new entity still retains the properties of the old entity. A fireman is still a man and thus he still has properties of a man, but he is refined even further with an occupation. A spaceship is still a ship, but one that can fly in space.

AVX470 is refined and "isolated" colostrum antibodies, but it still contains the same constituents of colostrum - casein, whey, lactose, immune factors, antibodies, etc, etc. The is not speculation but fact, as the chemical analysis of AVX470 will reveal the same thing, albeit in minor quantities. You cannot completely isolate one component of something without modifying the chemical content of it.

Again, I encourage you to get in touch with avaxia biologics and their scientists will tell you the same thing. I called them up and they told me that it was refined colostrum (which it is). Don't take it from me. The disclaimer in the packet was put in because it's accurate to a T and that it does have lactose, casein and whey in it.

It does not have anything to do with minor contamination, as the underlying chemical process of lactose, casein and whey remain unmodified. It is not completely "isolated". People who have those inherent dairy sensitivities will react to it, the same way celiacs react to gluten in wheat.

From the packet I have on it, given to me by the company:

Since AVX470 is derived from milk a product, it is possible that AVX470 could cause side effects due to an allergy to milk protein.

You have a belief system that prevents you from using logic. All of us resort to using the triune systems in the brain whenever what we are taught is questioned. That is so very reptilian of you and your brain.

And I tried to help you, but you are clearly a lost cause.

Post Edited (Guardian7) : 5/3/2014 6:25:55 AM (GMT-6)

If something is developed that works for me, I can't be worried about what the animals ate, or how much money "big pharma" makes from it, or the religion or color of the people who make it, or any other completely unrelated issues. If it gets me into remission and keeps me there, and if my insurance pays for it, I'm using it.

Hence, Remicade. My primary concern about changing to an oral TNF blocker would be that the cost would be prohibitive for me because of the way my insurance is structured.

Sorry to interrupt the never-ending argument.

Right, now let's start telling people with celiac disease to eat a modest, chemically isolated variation of wheat gliadin. The same principle applies to the dairy constituents in colostrum. By avaxia's own admission, it has lactose as well as casein in it, meaning they weren't able to refine the isolation process to make just pure antibodies alone as you just said. Let's completely deny what they just said about milk allergies now and the side effects listed - bloating, flatulence, nausea, diarrhea - all of which happen to be the same as those with case/lactose issues. Let's just throw that under the water and pretend it doesn't exist.

Better yet, let's wait for a franken variation of wheat gliadin where the gluten has been completely isolated out. Good luck getting someone with 20 years experience as a chemical engineer to do that. There's a nobel peace prize waiting for YOU to do just that because celiacs will be all over it.

They classify it as colostrum because it is colostrum, albeit an isolated one but with the dairy chemical constituents (lactose, casein, whey) still in tact. Talk to the people who worked on it. At the end of the day you will believe what you want to believe.

I'm done here.

Post Edited (Guardian7) : 5/3/2014 7:53:32 AM (GMT-6)