And on it goes! Day two of ADA has been terrific. Here are ten items of interest ...
1. In a session that was packed to overflowing – seven rows of chairs were set up in the hall outside the room to accommodate the overflow - Dr. Tim Heise offered a thorough comparison of NovoLog, Humalog, and Apridra (glulisine), Sanofi-Aventis’s rapid-acting insulin analog that was approved by the FDA last year but has not yet been launched in the US (why? apparently they want to get the pen first - it's all so complicated) though some physicians now have it (we have not been blessed with samples ourselves). Contradicting chatter that we heard at the ADA last year and which has resurfaced in other contexts, Heise found no statistically significant differences between the onset of action of Apidra versus either Humalog or NovoLog. That was sort of what had been exciting - insulin is too slow! - but it will also be fascinating to see how Apidra is marketed with Lantus, i.e., whether we will see more promotion of prandial insulin, which it seems we really need. BUT (!) of course prandial insulin is far more complex to dose than basal insulin, and Lantus success has been founded on simplicity - we look so forward to watching this.
2. It was very interesting to see more Byetta data - the A1C effect at 82 weeks was sustained, unlike most oral drugs to treat type 2 and, AND, the weight curve continues to slope down – weight loss actually continues to get better at 82 weeks versus 52 weeks. We were wondering about two-year data and we heard at the end of the session that at two years, A1C impact continues to persist and that weight loss also (!) continues – about 11 pounds two years out, so it sounds. Excellent.
On the Byetta-versus-Lantus front, study (26-week, multi-center, open- label, randomized, two-arm, parallel trial) showed that A1C effect was the same (the same as the insulin that has been a smash commercial success – basically down a point with half reaching 7% or lower A1C) with the difference that those taking Byetta experienced weight reductions and those taking Lantus gained weight – a difference of about nine pounds (those taking Byetta were down five pounds on average after six months, while Lantus users gained four pounds). We’re not sure what average weight gain is for Lantus – an average of four pounds up sounds a bit high – but clearly relatively speaking, Byetta wins. Now, which is easier becomes a key question – it’s no doubt that much of Lantus’ success has been due to the simplicity of the treatment. Byetta looks pretty simple too. There are side effects associated with both (nausea with Byetta, probably greater fear of hypoglycemia with Lantus, although actually, actual hypoglycemia was similar between the groups) and although it doesn't sound like nausea is such a big deal - it isn't nothing but the fact that people see how Byetta works immediately is a real positive (people often need to wait weeks and weeks to see a TZD impact for example - not a deal breaker for TZDs, just not a positive).
3. Symlin sounds like an official sleeper drug. People (yes, n is low for my discussions) like this drug - it's wonderfully hilarious, actually, they really can't tell you why, but people who are willing to take the shots seem pretty happy. Must say, from perspective of type 1 patient - so SO great to hear about a positive new therapy. "It's, um, it's really great, I just feel a lot better. Why? Um, I don't know. I can't really explain it. I just, um, really like it ...." We think it's all about post-prandial control, which has never been a big focus. This drug is also highlighting what's wrong and difficult about insulin. We heard tonight about a 300-pound patient of a noted endo whose weight -- and yes this is hugely anecdotal! -- dropped to 180 and whose insulin was cut by a third. "Oh, so she took Byetta," said a fellow conference goer. No, this was Symlin! Yes, n=1, etc - but what a story.
4. Merck and Bristol-Myers Squibb have unveiled a brand name for muraglitazar: Pargluva, which hints at the drug’s class identification as a dual-PPAR agonist and the word glucose. They had a long line of people at their booth, where they were engraving fountain pens with healthcare provider names.
During the Merck/Bristol-Myers Squibb corporate sponsored symposium, Dr. John Buse elucidated the adverse event data arising from a study presented at the American Association of Clinical Endocrinologists meeting a few weeks ago that compared 2.5 mg and 5 mg muraglitazar in terms of blood glucose and lipid control. 10% of patients in the study had edema at baseline, and in the course of the study edema rates ranged from 8–11%, which was not substantial compared to the placebo group’s edema rate of 16%. As one might have expected, slightly more edema was detected in the 5 mg dosage group than was seen in the 2.5 mg group. One case of congestive heart failure was seen in the 2.5 mg group. Two percent of placebo takers discontinued treatment because of edema but no patients taking muraglitazar discontinued because edema. We look forward to hearing “more on mura” at the late-breaking sessions.
5. In Paradigm Shifts in Insulin Treatment, sponsored by Pfizer and Sanofi-Aventis (the biggest Big Pharma force, of course, behind inhaled insulin), it was stressed that insulin as well as insulin sensitizers earlier in a treatment course may have greater protective effects for beta islet cells. As we have known, use of GLP-1 in rodent studies has shown to increase beta cell mass. Use of TZDs may also be effective, due to decreased glucotoxicity, apparently. Protective effects apparently occur even when therapies are of limited duration, it was said. A Turkish/Israeli study, where intense insulin treatment lasted only a week, still produced post-trial sustenance of glycemic levels. It will be interesting to see how beta cell function results emerge - we're aware this is very hard to measure, but from our discussions with HCP, we believe sustained A1C reductions may be accepted as a surrogate.
Inhaled insulin was positioned in this session as providing a patient-friendly insulin delivery method, in contrast to multiple daily subcutaneous injections. Compared to other alternative delivery methods, we were told that inhaled insulin allows for greater diffusion due to its greater vascular surface area (1000x greater nasal SA). The creation of pulmonary antibodies was not explored in depth but was acknowledged as requiring more investigation.
On a different insulin front - have you heard of insulin-eluting stents? We had not, until we heard about a company called Conor. We'll have to check that out. Another interesting company is Neurometrix. We typed it into yahoo finance and see that it's got a market cap under $200 million and the stock price has doubled since last year's ADA - we never recommend or even advise on stock investments, but we do watch the financial side and movement like this always makes us make a double take (in our head if nothing else.) This company is all about proprietary products used to diagnose neuropathies from what we just learned - we don't know much more at this stage, but the most serious neuropathy is a major unmet need, major expense ... major opportunity to help patients ... we'll do our research. We'll also look more into insulin-eluting stents, which sounds quite interesting in light of potential non-glcyemic benefits.
6. This is a meeting where the benefits and drawbacks of TZDs have been widely discussed. Lots of talk about weight gain and edema and CHF and then lots of discussion about how the use of TZDs can curb inflammatory effects on vasculature following internal trauma, can reduce inter-medial coronary artery thickness, can produce a decrease in C-reactive protein halting inflammation. We need to follow this further. We also hear a lot about how the kind of weight gain is the "good" weight gain and we're very excited to hear that from a technical perspective though we don't think most patients really care. After conversations with PCPs, we're not sure they care either - if the patient leaves the practice, they leave the practice, and there's no opportunity to help them ....
7. Dr. Spiegel, Director of the NIDDK, said that islet/beta cell biology is at the heart of not only type 1 diabetes, but also type 2 diabetes. The Beta Cell Biology Consortium shows great promise, with a mission to advance understanding of pancreatic islet development and function and to develop a cell-based therapy for insulin delivery. Have a look at the website: www.betacell.org. For obesity, Dr. Spiegel called www.obesityresearch.nih.gov the “one-stop shopping” site for finding out what’s going on in the science world of obesity. Wonderful resources.
8. Dr. Dorothy Becker challenged the current classifications of diabetes. Instead of using type 1, type 2, atypical diabetes (ADM), maturity-onset diabetes of youth (MODY), and secondary diabetes, Dr. Becker recommends that we move to the following three classifications: IDD (insulin deficient diabetes), IRD (Insulin resistant diabetes), and IDRD (insulin deficient resistant diabetes). Her discussion of “double diabetes” – patients who have both type 1 diabetes (autoimmune) as well as type 2 diabetes (insulin resistance) was fascinating.
9. We’re hearing a lot about obesity at this meeting and will be writing about this in more depth in our newsletter, particularly about Acomplia. As in past years, we’ve heard it stressed in many sessions already that people do not need to drop down to the recommended BMI levels in order to achieve significant health benefits. A modest weight loss, of 5-10% from baseline, can help a great deal (from a low base). Would that patients had been therapies and technologies to help them reach even this more modest goal.
10. Dr. Richard Nesto from Harvard Medical School and the Lahey Clinic Medical Center said that there may be an application of TZDs to non-diabetic patients – pre-diabetes, in other words. We’re staying tuned on this front. We would imagine given the adverse event rate (edema, congestive heart failure, oh, and weight gain), prescribing TZDs off label at this point would be quite brave. However, we’re extremely interested to see what the pre-diabetes trials show – staying tuned for now.
