Monday, October 20, 2014

Upcoming 11/3/2014 FDA-DOC Meeting; Concerns About FDA Biosimilar Guidance(s)

At this point, I don't think its really necessary for me to repeat too much of the content that is already circulating within the diabetes online community of blogs about the forthcoming Monday, November 3, 2014 meeting  from 1:00 pm-4:00 pm ET with the U.S. Food and Drug Administration (FDA).  But I WILL say that collectively, over the past year, the diabetes patient community was able to accomplish something truly quite extraordinary.  You should know about that, and even better, you also have a chance to participate in that!

Specifically, in 2013, the diabetes online community started a petition (see, which asked the FDA to devote one of its planned public meetings to diabetes.  For those who don't recall or never heard the sordid history, the short story is that back in 2012, FDA announced that over the next five years, it would be conducting at least 20 meetings on various conditions ranging from Chronic Fatigue Syndrome to Narcolepsy to Irritable Bowel Syndrome.  FDA pre-selected the diseases it would address in the first half of those meetings, yet miraculously, FDA did NOT originally plan to hold a patient meetings to discuss diabetes.  There were only four remaining slots open, and that's where we as a patient community came in.  The basic idea is that such a meeting would help to identify what barriers still exist that prevent the most effective treatments, and what the FDA can do to solve these problems.

I find it interesting that for all the lip service public health officials, including FDA and others, give to diabetes as an epidemic, complete with threatening stats such as more than one in five total U.S. healthcare dollars being spent to care for people with diabetes, and estimated costs of diagnosed cases of diabetes now totaling more than $245 billion (and growing).  Yet apparently, FDA thought it already knew what people with diabetes need and want.  (In fact, I have written in the past that FDA relies almost exclusively on the "surrogate endpoint" of HbA1c, catch my 2007 blog post at, often disregarding everything else, as long as a treatment reduced someone's HbA1c.  But it was the diabetes patient community which felt that FDA excluding diabetes (all types) was a big oversight, and the online petition collected over 7,000 signatures!  That, combined with our increased activism in recent years, including commenting on draft guidance documents, attending review meetings, etc., and I guess that FDA agreed that diabetes activists should be entitled to a meeting with them.

I should add that FDA hasn't really been overwhelmingly in favor of the idea (truth be told, they're used to working with industry [indeed, many FDA staffers are former industry people], but not very used to working with actual patients, so we ARE a bit scary to a group of people used to talking with and amongst themselves), but they're under tremendous pressure from the U.S. Department of Health and Human Services which manages FDA to become more "open" in the ways it does business.  Truth be told, I think the patient-led "Strip Safely" [] initiative kind of scared the crap out of FDA.

Having said that, it does seem that the medical device division within FDA appears to be the most receptive to this particular patient meeting, as the drug and biotech divisions don't yet seem to be completely onboard, with some rumors circulating that one of them actually cancelled its participation in the November 3, 2014 meeting.  But if the first meeting goes well, that may convince the laggard divisions to join in for future patient discussions.

A while back (in July 2014, diaTribe first wrote [] about the upcoming November 2014 meeting, and even offered patients an opportunity to email them with thoughts, see the aforementioned link for details).  As is my nature, I emailed them with two of my biggest concerns.

The first comment I submitted was about FDA's lackluster (which is putting things mildly) follow-up on post-marketing analysis and asked if patients might play a role in that, such as by filing Citizen's Petitions.  For the record, on that issue, several major medical journals show that something like only about half of all post-marketing analysis studies are even submitted as the law requires (and sometimes only because state court challenges mandates it), and even then, it often takes biotech, pharma and medical device companies nearly a decade to do what they agreed to when they received conditional approval for the drugs or devices.  Post-marketing analysis has come to be viewed by industry as a de-facto approval, and FDA's lack of follow-thru and enforcement has helped to create that situation.  There are examples where post-marketing analysis have been submitted (think of type 2 diabetes drugs like Avandia and Actos) which have revealed some truly frightening results and led FDA to add warning labels after they were already being marketed, but even that only happened after doctors like Steven Nissen at the Cleveland Clinic really pushed the issue.

Beyond that, I also wrote about some major concerns I have with the FDA and their biosimilar guidance.  FDA is required, in accordance with details outlined in the Affordable Care Act, to outline guidance for industry on biosimilars.  They did release initial draft guidance (three documents, no less), but a year after the comment period ended, they did something totally unprecedented.  Rather than issuing final guidance, they released yet another guidance document!  That was really confusing for me, and I don't think I'm a stupid person.  How did the new draft guidance document relate to the other three draft guidance document FDA already released?  What would they do next?

My second question was more of a concern.  My readers may recall that I have long been pushing the idea of follow-on biopharmaceuticals or biosimilars.  I first blogged about it in January 2007 asking why the hell we still didn't have generic insulin (see for details, and subsequently blogged about the various delays and issues related to that).  Last year, we finally got the original draft guidance FDA released on biosimilars (or "follow-on" biopharmaceuticals as FDA calls them and I submitted a laundry list of concerns, not the least of which was lack of clarity on biopharmaceuticals such as insulin which is governed by the Food Drug and Cosmetics Act, not the Public Health Services Act which governs most other biopharmaceuticals, which they went out of their way to note was only applicable to drugs governed by the Public Health Services Act but did provide some guidance as to FDA's thinking about biosimilars overall.  In my original comments on the first biosimilar draft guidance, I said that FDA needed much more clarity on which instances a biosimilar would be considered bioequivalent to the original molecule (a true generic).  I don't think they can ever really be considered a true generic, as master cell banks and process controls are different with each manufacturer, but unless the FDA spells that out, they've got room for issues, and insulin, which is among the most widely-used biotech products, is likely to see the results first, so I argued that was kind of big deal FDA needed to address.

Lilly's Lantus Biosimilar Has More Hypoglycemia in Patients With Type 1 Diabetes

Right now, because its grandfathered under the Food Drug and Cosmetics Act, insulin is still considered a "small molecule" drug and manufacturers can use several regulatory pathways [including the the 505(b)(2) pathway, which is not available to manufacturers of other biopharmaceutical products like vaccines].  Indeed, Eli Lilly and Company and partner Boehringer Ingelheim already have a biosimilar to Sanofi's Lantus (insulin glargine rDNA origin) which FDA already granted tentative approval.  Lilly is calling it Basaglar (peglispro rDNA origin).  But here's the thing: Lilly will be competing with Sanofi on price, which will likely win them coverage on a number of insurance company formularies.  Normally, that's a good thing, BUT … peglispro is not glargine, and the trial results have already revealed some troubling differences.  FierceBiotech, which was reporting on Lilly's press release how their biosimilar version of Lantus was supposed to be "better" than Sanofi's, this not-so-little tidbit was revealed (see for the article):

Just to quickly re-summarize:

Lilly also was forced to concede that in one of the two Phase III trials [specifically, the leg on patients with Type 1 diabetes] there was a statistically significant increase in daytime hypoglycemic events, an important safety measure, compared to Lantus. Even with an approval, any safety issues could carve out market value from a new diabetes treatment in this hotly competitive space.

The results from the two Phase III studies IMAGINE-1 and IMAGINE-3 in type I diabetes completes the trials planned for peglispro, and leaves Eli Lilly on track to file for an approval in the first quarter of next year.

Holy shit!  This is kind of very big deal, especially for insulin-sensitive type 1 patients with impaired hypoglycemia awareness.  Yet Lilly is busy saying how much better peglispro is to glargine (its not, its merely the same, unless you think that a statistically significant increase in hypoglycemia isn't a big deal).  Do you want your insurance company to switch you to this because its cheaper for them, but is more likely to increase your liklihood to have hypos?  I don't!  I expect to express my concerns to FDA!

Back to FDA-DOC Meeting

Back to my comments to diaTribe/Close Concerns about the November 3, 2014 FDA patient meeting.  Following the FDA's draft guidance for biosimilar guidance, FDA then did something unprecedented.  Rather than releasing final guidance on biosimilars, it instead released yet another guidance document.  I must admit that FDA move confused me a lot.  How did the new guidance relate to the original draft guidance?  What is/was supposed to happen next?  If I don't understand it, should other patients be expected to?!

I admit that I was totally confused by this FDA move, but I suspect many others were, too, because FDA has yet to release any final guidance on biosimilars even though it is obligated under the Affordable Care Act to do so.  My question for FDA is if industry and doctors don't even understand what FDA did, how are laypersons in the patient community supposed to?

To be sure, I think I could speak to FDA by myself for a long time with a long list of questions, but I like to think of this move as a first step in actual patient engagement.  Remember, FDA works for U.S. taxpayers to keep patients safe, they do NOT work for industry.

That meeting is scheduled for November 3, 2014 from 1:00 pm-4:00 pm ET.  One area that would help is to take a short, 5-minute survey to help the folks at diaTribe/Close Concerns summarize what areas of concerns matter to people with diabetes, and all you need to do is visit to take that survey.

To participate in the actual November 3, 2014 FDA meeting's webcast, you first must register at  Once you're registered, FDA will send you all the relevant information on how to join from 1-4 on November 3, 2014.


Laddie said...

Excellent in-depth and interesting blogpost, Scott. Your 2007 post was also incredibly prescient for issues continuing today. I was not aware of how few things besides A1c levels were considered when it comes to medications for diabetes.

StephenS said...

Scott, I absolutely share your concerns. Thanks for helping me understand (or not understand, as in the case of the additional draft guidance).

Jenny said...

Thanks Scott! I just filled out the survey.

P.S. I really appreciate your tweets which are just about the only ones I read daily.

--Jenny Ruhl