All of us in the Diabetes Community often wonder: What might the future of insulin look like, and how far out is the exciting new stuff we're hearing about?
Well, we have a snapshot of some of the latest developments, but keep in mind that answers to the really key questions that resonate through all of this are elusive; no one really knows, but they sure like to guess.
- A small biotech firm in Indiana that promised to pave the way to generic insulin is on the verge of foreclosure and shutting down for good, short of ever getting off the ground and starting its novel insulin-producing process.
- One small company is in late-stage clinical trials for an oral insulin pill, while others are exploring new formulations for inhalable insulin and also injectable nanotechnology that would respond to blood sugar levels in a person's body and react by dosing insulin.
- Other leading researchers think they've better pinpointed how insulin works in the body and that's making the research community all excited about future insulin.
- Yet, key regulatory guidance that could help boost this revolutionary biosimiliar insulin manufacturing world seems to be stalled, just waiting for someone to pull the trigger and put it all into motion.
- The large insulin producers are all working on their future insulins, but these remain in the R&D pipelines and are at least a few years off from reaching market (read: hype vs. hope category).
No surprise that the bottom line is this: despite all the buzzy headlines about new breakthroughs in futuristic insulins, there's little happening outside the research labs right now. It's still pretty far off from actually getting into our syringes and insulin pumps.
Yet although progress is slow, there are still a number of things happening on this front that are worth knowing about...
The Big Three
Right now, the scene is pretty much as it's been for the past decade -- a few fast-acting insulins (Humulin R, Humalog, Novolog, and Apidra) and a scattering of long-acting insulins, but nothing new. Sure, the big three insulin-makers -- Lilly, Novo, and Sanofi -- are developing their own varieties of long-acting basal insulin that would improve what we have now, but those are at least a couple years out in the pipeline.
At the recent Lilly Diabetes Blogger Summit, two Lilly execs -- David Moller who heads the endocrine and vascular research, and David Kendall who's in Lilly Diabetes global medical affairs -- described smart insulin as "aspirational" and "over-hyped in timeline." Lilly says it hasn't invested as much into smart insulins as others, but they are looking at the issue and other research for possible clues on how to develop smart insulin down the road.
Sanofi does list smart insulin on their "future directions" pipeline page, but it's listed dead last in a lineup of over 30 new drugs they're exploring (?)
An interesting item that Lilly execs shared with us was that during these clinical studies the FDA does not focus on therapeutic results, like CGM data or blood sugar readings that might indicate a PWD is achieving better control. Weird, right? Instead they're just looking for general evidence that the insulin in question is doing its job in real-time, and will probably work for most patients based the representative study sample.
With the many data analysis and regulatory hoops in place, it's no wonder it can take so long to get some of these products to market.
"Faster insulin is doable, and that's what we have in our active pipeline," Moller said, while his colleagues noted that the next 2-5 years will see acceleration of new insulin development and clinical trials, and hopefully getting through the regulatory process.
Novel Insulin In the Works
Meanwhile, the smaller outfits trying to forge new insulin-making ground have the most exciting prospects. There's Mannkind in Valencia, CA, that's making its inhalable insulin called Afrezza, and Israel-based Oramed that is in late-stage clinical studies on an oral insulin you'd take as a pill for type 1. Another is Connecticut's Biodel that is currently conducting patient trials on a rapid-acting prandial insulin called BIOD-123, and it's also developing a U-400 concentrated insulin that would go up against Lilly's version and be faster than what currently exists.
But in Cleveland, OH, one startup seems to have the most exciting research to report in recent months. Thermalin has been capturing headlines of late regarding its research on new insulin that would be faster and more concentrated than anything we've seen to date. A point of pride this little company likes to tout is that they have the co-inventor of Humalog insulin, Dr. Bruce Frank, in their ranks to help forge the path forward.
"We have a whole pipeline of products in the works, because there's groups of people with diabetes on insulin whose needs aren't adequately being met by the insulin on the market today," Thermalin CEO Rick Berenson told me by phone.
Specifically, he said Thermalin's working on three exciting things:
- A new concentrated U-500 insulin targeted at those PWDs with high insulin resistance taking 150-200 or more units per day. Unlike the existing Lilly version of that concentrated insulin that can take as long as 24 hours to absorb, Berenson said his company's version would have activity curve closer to the existing fast-acting insulins of three to five hours. Thermalin is working to get that into human clinical trials by the end of the year.
- New ultra-rapid-absorbing insulin that would be 30-50% faster than what's on the market today. They'll be starting on that the coming months, and
- A new stable basal insulin that wouldn't need refrigeration and would be more suitable for mail order shipping.
Thermalin is also excited that one of its own, Dr. Michael Weiss, is part of an international team of researchers that's gotten a "first glimpse" at how insulin actually interacts with cells. They call it a "molecular handshake," and describe the discovery as one of the "top 10 milestones" in the history of insulin since the medicine's creation in 1921. Researchers expect that to open up more doors in the insulin-making world.
With a lot in their pipeline, Berenson says Thermalin isn't planning to get into the generic or biosimilar insulin R&D -- and he doesn't think that's coming to the market anytime soon, either -- mostly because of the limited regulatory guidance and all the hoops smaller operations will have to jump through that hinders them from competing with the bigger outfits like Lilly, Novo, or Sanofi. Still, all these smaller biopharmaceutical companies will create more competition, and hopefully force Big Pharma to rethink how it does business creating and marketing insulin.
Generics? Not So Fast...
Just south of Indianapolis in Greenwood (the city where I live and a couple miles from my house!), there's a small company called Elona Biotechnologies that has had generic insulin in its sights. But the company's had a rocky start in the past few years and whether it can get anything to market seems to be growing more unlikely as the weeks pass. Early in the year, the city found Elona in default on repaying $8.4 million incentives it had been given back in 2010 to help not only build a new insulin plant and hire workers, but to help get a generic insulin through the FDA process. That didn't happen and the city is fed up, saying in late May that it was close to foreclosing on the property and putting the brakes on the generic insulin plant.
A few months ago, I toured the still-under-construction plant that's been in the works for three years but hasn't been finished. Since then, construction has stopped and they're staving off foreclosure. I wasn't overly impressed with the founders, as it seemed like all they had were high hopes of getting this off the ground.
As much as I may want generic and less expensive insulin, it doesn't look like we're close to getting that anytime soon.
The ball is in the FDA's court now on releasing final guidance for biosimilar insulin, but what looks to be the most promising in the coming years is the faster insulins.
That is where I'll keep my eyes focused on the future, all the while continuing to fill up my insulin pump with whatever's on the market now and I can actually afford.
Because really, no matter how novel a new medicine may be, being able to get our hands on it is the absolute key issue -- no matter what the researchers might think.