1. Sean on May 24, 2012 8:00 AM writes...

I have to assume saying insulin (51 amino acids) is a big protein is referring to some other data? Are they pegalyting it as suggested in the linked article? The original paper mentions issue with diffusion out of the gut being an issue so there maybe a difficult trade off going on.

2. Curious Wavefunction on May 24, 2012 8:40 AM writes...

Is an insulin peptidomimetic an inherent impossibility?

3. Rick Wobbe on May 24, 2012 8:56 AM writes...

Exubera's failure was a good example of how, for entirely non-scientific or pharmacologic reasons, one drug's fate can needlessly torpedo an entire drug class in the minds of investors and industry management. The failure had nothing to do with inherent pharmacologic problems of pulmonary insulin vis a vis injected insulin (in fact, inhaled insulin has remarkably good PK/PD and tolerability). The problem was disappointing sales, probably stemming from Pfizer's clunky delivery system, which patients just didn't like. Having worked at another company developing an alternative inhaled insulin that would have circumvented those limitations, but was essentially canned after Exubera's disappointing sales, I saw a lot of healthy babies get thrown out with the bath water.

4. Electrochemist on May 24, 2012 9:14 AM writes...

@ #3 (Rick Wobbe) - Exubera and other inhaled insulins were "canned" because insurance companies would not reimburse for the higher costs of the delivery method. There was no obvious improvement in patient outcomes to justify the higher prices (in their analyses). While it may look like it was a "poor sales" issue, it was actually a reimbursement issue.

5. Dave on May 24, 2012 10:05 AM writes...

Will this be a normal (fast acting) type of Insulin, or more of a slow acting Insulin analogue, such as Insulin Glargine?

http://en.wikipedia.org/wiki/Insulin_glargine

Dave

6. Rick Wobbe on May 24, 2012 10:07 AM writes...

#4 Electrochemist, As far as I'm concerned they're two sides of the same very thin coin. Sales and marketing failed to take reimbursement into account, which led to weak sales, a sadly familiar tale. For what it's worth, the delivery methods of many other programs were substantially different (dry powder) and cheaper than Exubera's, which required a propellant, which only adds to the irony.

The more important point is that the failure was for sales and marketing reasons, not because of any pharmacologic inferiority. Had the salient technical differences been appreciated by decision makers, I would like to think the outcome would have been different.

7. Hap on May 24, 2012 10:29 AM writes...

I thought inhaled insulin had two "bonuses" which are not present with the ingested variety - one, it caused some lung impairment (which wasn't good to start with and might have caused issues with some sets of users) and, two, there was the potential for the inhaled insulin to increase cancer risk. The latter may have been a blip, but hurting lung output for no particular gain (in dosage - you still have to stick yourself to get blood glucose levels - or in compliance) and lots of financial loss does not seem to be a winner.

Varying dosage for ingested insulin would seem like a problem.

8. Anonymous on May 24, 2012 10:39 AM writes...

#3 - Would that have been the place in Chelsea, MA? Beautiful plant, fun place to work.

9. Jake on May 24, 2012 10:43 AM writes...

I don't know anything about insulin, but is anybody working on a sublingual variety?

10. Rick Wobbe on May 24, 2012 10:48 AM writes...

#7 Hap, Those were two concerns about inhaled insulin, and indeed any inhaled drug, that were addressed to the FDA's satisfaction in Exubera's clinical package. Whether one or both of those problems would have emerged as significant in the market, which IMO would have constituted a more legitimate reason to throw a wet blanket over the whole therapeutic approach than "marketing botched the price calculation", we'll never know.

11. ronathan richardson on May 24, 2012 11:17 AM writes...

Does anybody know if their candidate (NN1953) is a peptide/peptide mimetic or small molecule?

Also, you put it very well in describing digestion, Derek--if we were able to absorb proteins through the gut, we'd get all kinds of toxic stuff everytime we ate a meal. Especially if it entered cells--imagine the incompatible protein complex. So really we've evolved to destroy all proteins we swallow to avoid this. Never thought of it this way, as obvious as it is.

12. Hap on May 24, 2012 1:46 PM writes...

Even if Exubera had been cheaper and hadn't required a bong to deliver, loss of lung function and possible cancer would have been difficult to circumvent. On the Exubera posts, other than the few commenters who complained about the retraction of Exubera (who probably constituted a significant portion of its purchasers), people complained primarily about the needles for glucose monitoring being much more annoying than the insulin injections themselves. If you don't solve a problem in the patient population and generate new ones, why would you think your product is going to sell a lot?

I thought Generex was working in this field. Where's their product?

13. Myma on May 24, 2012 2:48 PM writes...

A couple years ago, I had to do a due diligence on oral delivery technology for biologics. The competitive information we compiled showed that based upon public domain disclosure, something on the order of 75 companies had in the past two decades worked in the area, not including university groups. Of that 75ish number, about 10ish still seemed to be working actively in the area. Those 10ish include a couple of companies working on humic acid complexes to improve bioavailability. Basically, dirt extracts. Dirt, ground up with a protein, and put into a gelatin cap.
Anyway, based upon the numbers, I was and am highly skeptical.

14. AndD on May 24, 2012 2:51 PM writes...

Oral insulin seems a massive challenge - not only do you have to get therapeutic levels absorbed, it also needs to be reasonably consistently absorbed, patient to patient, dose to dose. If it can be done though, I would have thought it would open up other opportunities for peptide/protein oral delivery - big "If" though.

15. mad on May 24, 2012 9:04 PM writes...

People have been working on oral insulin since insulin was discovered.

There are pretty much no new ideas.

Just new penetration enhancer mixtures and non-specific protease inhibitor effects that get diluted out or precipitated out in vivo.

Periodically this idea resurfaces, executives get excited with the "billions upon billions" hype and companies waste millions on it. Evently it fails and goes dorment again for a few more years...

16. Waverunner on May 25, 2012 4:39 AM writes...

I still don't understand, how they want to circumvent the problems of absorption within limited time and changing environment in comparison to fast acting injected insulin. An alternative method, which should become standard in the future could be this:

Device May Inject a Variety of Drugs Without Using Needles

http://www.sciencedaily.com/releases/2012/05/120524134703.htm

ScienceDaily (May 24, 2012) — MIT researchers have engineered a device that delivers a tiny, high-pressure jet of medicine through the skin without the use of a hypodermic needle. The device can be programmed to deliver a range of doses to various depths -- an improvement over similar jet-injection systems that are now commercially available...

17. Kling on May 25, 2012 5:33 AM writes...

The challenge in diabetes management is administering correct levels of insulin when required. Currently injection pens are not painful because the needles are so small (I know first hand, I am type 2), and fingerstick monitoring is a hassle. So patient compliance stinks. The killer app for diabetes is not oral delivery, but a biological transplant approach. This has been tried for decades without success, because of the difficulties in islet cell transplant (rejection, source of islets). Gene therapy of glucose responsive promoter with insulin DNA has been been attempted experimentally, but don't know how successful. I think a glucose responsive, insulin expressing engineered cell line coupled with Neurotech encapsulated cell technology would be the way to go, but long way off. So many hurdles for such an important disease.

18. anonymous on May 25, 2012 6:18 AM writes...

As Derek alluded to, variability in absorption leading to variability in insulin dose delivered will lead either to insufficient efficacy (i.e., a slow death) or potentially rapid death due to hypoglycemia. Take your pick???

19. Electrochemist on May 25, 2012 7:17 AM writes...

The bioavailability of inhaled insulin is about 10 to 20% that of a subcutaneously injected suspension (see, e.g., Ref 1, below). So, even under the best of circumstances, the cost of raw materials would have been 5 to 10X that of vial/syringe delivery (ignoring the cost of the delivery device completely).

Couple that incontrovertible fact with the knowledge that (a) the 80% to 90% that is not absorbed in the lungs has to go somewhere, and (b) the best possible scenario for the patient is that the absorbed material is just equal in efficacy to an sc injected suspension.

Given the rise of insulin pumps and long-acting GLPs, the business case for R&D spend on development of inhaled forms of insulin is highly questionable. I can't see how the economics of orally dosed insulins would be much better.

(1) http://care.diabetesjournals.org/content/25/12/2276.full

20. Dave on May 25, 2012 10:04 AM writes...

Has there been any work done on transdermal patches for insulin delivery?

Dave

21. Morten G on May 25, 2012 10:31 AM writes...

There was a once-monthly injection dermal glucose monitor company but I think they went bankrupt.
The idea was that a tiny capsule was deposited in the same depth as tattoo pigments and you could then monitor glucose levels via FRET by putting a monitor on your skin. Biodegradable.

22. Eva Moeller on May 25, 2012 5:40 PM writes...

NN1953 is a basal insulin. I do not know how it has been modified to become a basal (long-acting) insulting, though - and can't seem to find info. Novo Nordisk has partnered with Emisphere and Merrion (absorption enhancers) on this project.

Somehow, I'd be betting on the GLP-1's for oral administration, though. Seems less cumbersome and less important on the dosing. NN has two programs running for oral GLP-1s at present, in parallel with the oral insulin.

23. p on May 25, 2012 11:33 PM writes...

Forget all the technical details. As a type 1 diabetic for very nearly 30 years now, I rank having to penetrate my skin with a needle as somewhere between 20 and 25 on the list of "aggravating things that come with diabetes". I have no idea why so much money, time and intellect has been devoted to "solving" this problem.

Figure out how to measure my blood glucose better, faster, easier and more accurately. Figure out some way to automate delivery of insulin based on that reading. Figure out how to minimize the constellation of complications from the merely annoying to the lethal.

If you told me I could jettison everything else having to do with diabetes merely by injecting a modern insulin needle into my leg every 5 minute for every waking hour for the rest of my life, I'd probably do it.

24. Scheff on May 27, 2012 12:34 PM writes...

Check out www.tamarisk.com, they have just recently discovered oral insulin

25. Scheff on May 27, 2012 12:35 PM writes...

Check out www.tamarisk.com, they have just recently discovered oral insulin

26. Moshe Tritel on June 6, 2012 4:53 AM writes...

Dear Myma,

Would you kindly be in touch with me?

Moshe Tritel mtritel @israel-patents.co.il.

Thank you!

27. roberet on July 11, 2012 3:44 AM writes...

i thought they were doing research with inhaled insulin and Alzheimer's or dementia? if inhaled insulin helps would that be a mopre profitable market?

28. Dr DeBrouse on August 12, 2012 3:33 PM writes...

The correct website is www.tamarisktechnologies.com. I have a comment for the gentlemen who wrote this article; "how could you write such an article without considering the fact that Tamarisk Technologies has resolved oral insulin? Our molecular basis has been posted on our web for all to see for months and none can dispute it and in fact big pharma has validated the tech. I understand those mentioned in this story wish to be the one, well they've missed the boat I'm afraid.

29. Steve Powers on August 25, 2012 2:28 PM writes...

I just read an article at a division of ABC news at ABC Science online about an Indian Dr. who may be starting human clinical trials soon with a nano-particle pill.
"People with diabetes could soon take a pill of insulin-loaded nanoparticles instead of having to give themselves painful injections, Indian researchers say.
Professor Chandra Sharma of Sree Chitra Tirunal Institute for Medical Science & Technology presented the work this week at a biomaterials conference at the University of New South Wales in Sydney.
"We have already developed the capsule form of the insulin," Professor Sharma said.
"We have already tried it on pigs and rats."

30. Osman on October 27, 2012 6:40 AM writes...

when is comming type1 pills, l cant have insulin injection any more pls pls...

31. omamin on January 7, 2013 9:42 AM writes...

Check out this. According to them,( in fifth paragraph) high dose of insulin through oral route is not a problem as insulin pass through first pass metabolism in liver which reduce its dose to normal.
http://oramed.com/index.php?page=14

32. Dr Paul on February 13, 2013 11:27 PM writes...

Does anyone know if Tamarisk Tech finished their clinicals? It appears they never answer their emails or calls.