Tuesday, January 20, 2015

2014 Observations in Type 1 Diabetes Treatments

Happy 2015! Its no secret that I don’t blog like I once did, and the fact that I'm posting twice this month isn't necessarily a sign that is changing.  It’s not like I’ve disappeared (I still have a very active Twitter feed), but Google tried its best to kill blogs when it shut Google Reader down (that failed; I’m still using a different reader known as G2Reader which I think is a damn close replacement and they have a mobile app for Android, but nothing for Apple, sorry iPhone junkies), but many other people have basically given up on a truly open internet with the likes of RSS readers which paved the way to open communications for companies like Google and Facebook to capture that and try and make it proprietary). Be that as it may, I still blog every so often (at least occasionally). This is one such post. It could have appeared at the end of 2014, but I’m doing it in January 2015.

There were a lot of diabetes related news stories in 2014, yet not every story was in my opinion, really news (or even newsworthy!). However, at least few were at least worth acknowledging. Here are my picks for the biggest news items of 2014:

JDRF Names (Yet) Another New CEO, But Most Recent CEO Appointment Raises Questions About Organization's Internal Politics (Dysfunction?) 

In July 2014, JDRF named Derek Rapp as the organization's new President & CEO. While succession plans would ordinarily not be a big deal, JDRF has taken routine CEO replacement to new levels in recent years. Think about it: over the past decade, JDRF has had 5 new CEO's, which works out to an average of a new CEO every other year! That’s a downright shitty track record, and should be an incredible embarrassment to the organization, yet it keeps happening over and over, again and again.  Was the last CEO really failing?  No.  As I said, it appears that most of it's driven by internal politics among high-ranking board members of the organization, but I've grown tired of routine strategy shifts and the routine change in direction for this organization. Fundraisers and donors are being taken for granted, so I didn't raise any money for the JDRF this year, yet that didn't stop them from trying to mine their advocacy database for fundraising at the end of the year, just like everyone else does. I promptly deposited those emails into my trash bin. Every organization does mass emails at the end of the year so this wasn't innovative, it was just plain annoying.

But more importantly, JDRF needs to go back to a state where its fundraisers and donors are appreciated (one of the things former CEO Arnold Donald tried to do under his short tenure with the organization), because frankly, they've been taken for granted for more than a few years. While I don't agree with a lot of the Juvenile Diabetes Cure Alliance's objectives or conclusions, I do think they wrote one of the best posts of the year about JDRF's internal turmoil. For some reason, hardly anyone dared asked about the internal politics behind the change for reasons that escape me. But this article was well worth a read: http://thejdcablog.org/blog/2014/08/18/jdrfs-abrupt-ceo-transition-raises-questions (see also http://www.diabetesmine.com/2014/07/newsflash-ada-and-jdrf-change-leaders.html)

Now, I won’t kid you.

Being CEO sounds nice, but the pay isn't that really great, especially when compared to the private sector. JDRF doesn't pay that badly (for a non-profit), but most CEOs could make a LOT more money elsewhere, usually they’re there because they have a personal stake. That’s a fact. Nonprofits aren’t big-paying gigs, but they are ego boosters. But the CEO shuffle at JDRF? There’s more than meets the eye than we’re being told, and you have the right to ask questions. I don’t know much about Derek Rapp, but I will say that his board members shuffled Jeff Brewer out of office before much had really changed. Was he really doing such a lousy job?  No, someone on the board didn't like him, so instead, they put a guy who worked for Monsanto for years in his place.  Monsanto is a company best known for trying to hide genetically modified organisms from everyday housewives, but who knows, maybe he'll be more cut-throat in negotiations with big pharma and big biotech.  That much the JDRF could use.

By the way, did anyone notice how a few years ago the "State of the Foundation" addresses the JDRF organization once routinely gave suddenly stopped? Why … because its a pain-in-the ass to do? So what? That's why you’re being paid a hundred thousand+ dollars each year. We deserve that much transparency, also your industry partnership program which remains a complete black box for donors with no disclosure of anything (can anyone say how much money the organization has spent on the Artificial Pancreas project?), and don't go blaming industry for that. JDRF agreed to the gag orders, but why not insist on some conditions (milestones) for those gag orders remaining in place?! Just saying.

Sanofi: CEO Shuffle, Acquisition of the Global Rights to Market Mannkind's Afrezza, But Still Not Selling Everything It Could (or Should Be) to Americans 

Sanofi, at least in the U.S., has always been kind of an also-ran in the diabetes space. It is basically a one-trick pony with Lantus and everything else (like Apidra) being pretty minuscule. In spite of getting a lot of news in 2014 for Sanofi buying the rights to selling Mannkind’s new inhalable insulin Afrezza (and the technology for using it on other biotech medicines) globally, that was one of the previous, American-born and based CEO's moves, only now Sanofi has moved back to a France-centric company even though most of its money is made from elsewhere. We can still expect to see Afrezza in 2015, but don't expect it to be getting quite as much marketing attention as it might have under the company’s previous leadership.

Its not that Sanofi doesn't have world-class researchers (it was one of the first three companies along with Novo and Lilly to sell insulin, although it was formerly known by its German name Hoechst which still sells regular and NPH in Germany and Austria under the brand name Insuman), or a lengthy history in the diabetes space. It also is a leader in insulin analogues.  It has a 100-year history but it also has a history of management changes, most recently when the French government coordinated Sanofi's acquisition of Aventis to ensure a global pharmaceutical company remained based on French soil, even though most of its diabetes researchers are actually based in Germany, not France. Sanofi's diabetes business is really big, but consists mainly of a single product whose patents expire in 2015: Lantus (insulin glargine rDNA origin). But Sanofi could be selling old-fashioned Insuman products here today. Are those products going to make Sanofi a fortune? No way, but they might help get Sanofi on some more formularies!

If you're a one-trick-pony, they won't carry Apidra (insulin glulisine rDNA origin), either, and why should they? They are choosing Lilly over Novo nowadays because they’re offering low prices and a nearly complete product suite. Novo offers that too. Sanofi only sells two analogues in the U.S. today, whose patents are due to expire soon. If Sanofi wants to remain relevant, it should consider selling Insuman products here, too.

Fraudulent Research on Diapep 277, But Unless You’re A Hyperion Investor, Who Cares?!

This story was, in my humble opinion, the single biggest diabetes story of 2014.

For years (maybe even decades?) we've been hearing about a potential autoimmunity treatment for type 1 diabetes called Diapep 277. It was at one time owned by Aventis Pharmaceuticals (now known as Sanofi, see preceding paragraph for more on them). I blogged about it when Teva was paying milestone payments on it, but that ended, and now we know why (see my blog post at http://goo.gl/jmiNh for more detailed background).  But Diapep 277 has changed hands many, many, many times over the years. We never really saw much detail on how the product actually worked because it was, after all, proprietary information. A few d-bloggers have been questioning the lack of transparency about it for many years, among them d-blogger Joshua Levy [http://cureresearch4type1diabetes.blogspot.com/].

My take has always been I cannot question something I have little or no data on, so I took the company at their word (indeed, I still listed DiaPep 277 as a potential autoimmunity treatment a few years ago (see HERE). At the time, I thought it looked promising because Teva was still backing it, but the company never met Teva's milestones, so Teva was paid nothing and backed out, but Andomeda was undeterred and found a new sucker buyer in Silicon Valley. As it turns out, their word wasn't worth much, either, yet they still managed to sell their fraud to a less-than-careful Silicon Valley biotech company known as Hyperion Therapeutics, which had acquired DiaPep277 developer Andromeda Biotech in June 2014. I wanted to believe that there was some secret information Hyperion had access to, but as it turns out, it was all a load of crap, fraudulent from the very beginning, with made-up research results and studies. Not a good omen.

Frankly, I would expect Hyperion to have done much, much better due diligence, but apparently not. Andromeda played them like a harp. More than a few people should be fired for this at both companies (forthcoming lawsuits aren't going to be cheap.). Apparently, they (Hyperion) were fools. Big Fools. My opinion on this is that its yet another failed autoimmunity treatment, as ALL of them have been so, NOT ONE has succeeded so far, which should have you worrying about how seriously anyone is taking the idea of a biological cure for type 1 diabetes. Sure, there's still Tolerion, Inc. (formerly Bayhill Therapeutics) but they no longer have backing from Roche's Genentech unit, which in my opinion isn't necessarily a bad thing, since Genentech avoided spending a dime on it anyway, blaming things like "resource constraints"), and Macrogenics still thinks its treatment can work in certain people, but we don't have any imminent success stories on the autoimmunity front.

Author P.S., Feb. 17, 2014:  There was news in the Israeli business press today that the two companies have come to some kind of agreement, suggesting that outright fraud may be a bit of an overstatement (see http://iglob.es/?en1010763 for details).  Maybe, but I personally don't have much confidence in this as a potential Type 1 diabetes treatment anytime soon largely because the actual data has been kept hidden from the public.  Only time will tell, but this isn't the first failed autoimmunity treatment to make news, in fact, all have failed so far.

It's upsetting, but at least there wasn't any money (unless you're a Hyperion investor) from the likes of JDRF or the DRI or even ADA at stake here. But it also means we haven't witnessed a single autoimmunity treatment for type 1 diabetes that's made it to commercialization yet, either. This is yet another one in a long line of failures.

Rather than continuing to fund even more incremental treatment improvements, perhaps we should insist on more collaboration with other autoimmune disease foundations or institutes?

NIDDK won't even send the same person to Autoimmune Coordinating Committee within the NIH each meeting.


In spite of The Special Statutory Funding Program for Type 1 Diabetes Research, one might think NIDDK would consider it important enough to have dedicated resources they allocate to this cross-NIH program, but you'd be wrong. A different person, assuming NIDDK even bothers sending someone (sometimes they haven't), has showed up to every single meeting.

The Institute doesn't even acknowledge being a member. The real question we should be asking is why not? I've been bitching about this for over 5 years, and no one seems to care. Maybe they will when there's some success in disease states like Rheumatoid Arthritis? The leader of NIDDK is not even a specialist in endocrinology or nephrology, he's a hematologist.  That's fine if we're looking for a cure for lymphoma, but we want to cure diabetes.  Why the hell are we allowing this man to continue running the NIDDK … for years and years?  He stepped in as a temporary replacement, but never left the job.  Do we really need a hematologist making decisions for us? Not to be too cynical, but we'd be just as well off having a gynecologist run the show, frankly, they have just as much relevant training.

Yet I've been the only person questioning this choice of leadership. 

Maybe 2015 will be different?

Maybe patient advocates will raise the issue with our lawmakers?

Patient Advocates Increase FDA Presence (Some Staff Actually Know Us Now!!) 

Aside from these, there were of course, the incremental improvements, a whole lot of cost increases, but nothing really new. There's was news last week (from the J.P. Morgan Healthcare Conference) that Medtronic's Minimed 640G (with low glucose suspend) will finally be sold in the U.S. by April 2016, and the company is saying that overnight closed loop could be ready for sale by April 2017.

That's a impressive, but no offense to Aaron Kowalski at JDRF who was recently promoted to JDRF's Chief Strategy Officer, I've been hearing this fucking promise since 1978, and he wasn't even at the organization back then, but my parents were, along with others like Lee Ducat and Carol Lurie (who is now passed).

The artificial pancreas has had a gestation period longer than any diabetes treatment in history, so JDRF and others don't deserve to call it big progress, because that's an exaggeration. This means its only taken you 38 years to deliver on this device. I could jokingly say that’s still incredible in biomedical research, but I'd be lying completely.

I realize Medtronic can only do so much by itself, and in that regard, patient advocacy with FDA was very important in advancing this. But we only have FDA involved in the device side of the FDA, on drugs and biologics, they still aren't truly considering patient input yet as best I can tell (though occasionally they do vote in ways that are in the best interest of patients).

Unless, of course, you count the progress FDA has made in its interactions with patients. That was THE BIGGEST success so far. It still leaves much room for improvement, of course, but its still a very big deal in my opinion. Now if only we can get Janet Woodcock at CDER and her colleagues in CBER on board. Never fear. The explosion of nonprofits in diabetes with at least one saying this is their direction, so we can see what (if any) progress is made on this.

But its time for someone with more time and resources to do something on this; I've been plugging away since before 2005, and after a decade of effort on my part, these days, I'm a bit more focused on other parts of my life. Like planning for retirement with my spouse, buying a house, that kind of stuff. Make no mistake, I'm more than willing to assist where I can help, but I'm not driving this initiative unless someone asks me.

No comments: