Biologics, Part Deux

Reader, this will be a serious post in a second, but indulge me while I say:

Dear Cate Blanchett,

Due to egregious crimes against fashion, I am putting you on metallics hiatus until further notice. Please see Exhibit A and Exhibit B for recent examples of your transgressions. Until such time as you are deemed competent to engage in responsible shimmer, you are mandated to drab it down.

Thank you.

Sincerely,
Professional Critic

Back to our story. Perhaps you skipped my original post about biologics. It was Thanksgiving week and you were busy fretting about how to brine the turkey because the pot didn't fit in the fridge and wondering if it was cold enough to let the turkey brine outside without killing all your guests with salmonella. Understand, totally. But read it now because I am all geared up to write more about this topic. I recently learned that I have not one but TWO readers knowledgeable enough about biologics to gently nudge me when I start to talk out of my ass. Which happens all the time with alarming frequency hardly ever, but still. Thanks, Facebook!

So, last we talked, we got clear on what a biologic was and why it's not as easy to produce generically as a small molecule drug. If you're lost already, go back and read the damn post already. I'll wait.

We can't engage in a conversation about this topic specifically and generics overall without raising a glass to Henry Waxman. Waxman served as Chairman of the Committee on Oversight and Government Reform and was just appointed to be the Chairman of the Committee on Energy and Commerce, which is majorly big whoop. He also looks a little bit like a fierce woodlands creature:


























Which is in fact how he conducts himself. Check out legislation he has sponsored and you'll see he is le bomb to a nutter like me that believes in transparent government, oversight, accountability and generally that our government should not conduct itself in a totally douchey way.

Back in 1984 Henry Waxman and Orrin Hatch sponsored The Drug Price Competition and Patent Term Restoration Act, a mouthful now just called Hatch-Waxman. Hatch-Waxman paved the way for a much wider expansion of generic drugs by cutting the cost of generic approvals, allowing generic competitors to begin testing and development prior to patent expiration, and rewarded innovators by allowing for some patent extensions to compensate for longer regulatory approval processes.

A critical part of facilitating the expansion of generics has been the creation of the Abbreviated New Drug Application or ANDA. If they can demonstrate that their product is chemically the same, as effective and safe as the original, generic competitors can bypass clinical trials required by the FDA and make lower cost generic drugs available more quickly. Once that happens, additional generic manufacturers can do the same, further driving down the cost of the drug. If you're an even hardercore geek than I am, you can read more about the ANDA process here.

So, the question is, can the ANDA framework set up by Hatch-Waxman simply be applied to biologics, which we already know are way more complex than small molecule drugs?

To attempt to answer that question, I had to delve even deeper into worlds I only sort of semi-understand. Luckily, I found this article from the Duke Law and Technology Review which raised an argument against using the ANDA process for biologics: immunogenicity.

I am now way, way out of my league here but immunogenicity seems to be the measure of the immune response to a biologic. Too much of a response is bad, potentially deadly. But immunogenicity is not consistent between people and not consistent over time, so that it could be fine for one person but kill someone else or be fine for a year and then kill that same person.

To make matters slightly worse, scientists don't always understand what causes changes in immunogenicity. They could be genetic or could be caused by some additive, like silicone oil used to make glass pre-filled syringes. Srsly. I guess since sometimes even biologic makers don't always understand why their product works, or can't always make their own product correctly, I guess it follows that there would be even more unknowns in the attempt to create follow-ons.

Immunogenicity is a hot topic in the world of biologics. There's a whole conference about it next year in Germany where you can learn all you ever wanted to know about "confirmatory assay cut points, acid dissociation elution for ADA detection and incurred sample reanalysis." Yes! No idea what any of that means. I guess if I really wanted to know, I could shell out $2900 for this white paper, or just remain in the dark a little bit.

So what's going to happen? Will Congress do as the European Union does and mandate clinical trials to address immunogenicity? Or should the FDA be allowed to decide on a case by case basis, based on how complex the particular biologic is?

Or did this actually already get decided and I just can't Google worth a tinker's damn?

There are two take-home points to this story:

1. Anyone who figures out how to manufacture follow-on biologics without killing too many people is going to make assloads of money because a) these drugs are so ridiculously expensive even a 10% cost reduction would be welcome by insurers and b) these are so damn hard to make, you are not going to have a lot of generic competitors and your price won't be challenged. If you're contemplating a career switch and aren't science-averse, DO IT.

2. Biologics are the answer to our most shiteous illnesses: rheumatoid arthritis, breast and other cancers but they are redonk expensive. Making these therapies available to more people at a lower cost is a public health issue.

Now, I must have a glass of wine.