In the area of beta cell preservation, there's a (sort of) new name in the spotlight: Andromeda Biotech, Ltd. with its DiaPep277 treatment. Based in Israel, this company announced last month that phase III clinical trials showed significant preservation of C-peptide levels, a marker for assessing insulin secretion by pancreatic cells. Andromeda joins the ranks of companies like Tolerx and Macrogenics/Lilly, who've been vocal about their work to preserve beta cell functioning in newly diagnosed patients with type 1 diabetes.
DiaPep277 is a unique peptide now being employed to prevent the destruction of insulin-producing cells. The name may bring to mind that once-hot controversy about the removal of C-peptide from insulin analog products, which many patients believe may help prevent complications such as neuropathy and kidney disease, but experts have dismissed as too complex and expensive.
There is no connection between DiaPep277 therapy and that particular issue, according to Dr. Shlomo Dagan, CEO of Andromeda since its outset in 2007. Rather, his company is using C-peptide "as a way to measure insulin production" in the sense that C-peptide is a by-product of insulin production, so if it exists, it means insulin is being produced.
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To get a grip on this therapy, we turned to Professor Irun Cohen, who created DiaPep277 at the Weizmann Institute of Science in 1994. He explained that DiaPep277 is a synthetic peptide of 24 amino acids derived from the sequence of the human heat shock protein 60 (Hsp60). It actually works to modify the immune system, preventing the destruction of the pancreatic cells that secrete insulin, and preserving their natural function.
"Autoimmune diseases arise from the misbehavior of existing autoimmune lymphocytes (small white blood cells that bear the major responsibility for carrying out the activities of the immune system) that 'over-react' to normal tissues as if they were in need of repair." Therefore the most practical approach for science is not to suppress the autoimmune response, but to "re-educate" the autoimmune lymphocytes to respond appropriately, Dr. Cohen says, adding: "That is the basis for thinking about vaccination as a form of re-education."
DiaPep277 is different than immuno-suppressant drugs like Amevive or Rituximab, which aim to prevent the attack of activated immune cells on the pancreatic cells. "Our use of DiaPep277 is a way for us to talk to the immune system in its own language — to get the system to reconsider the way it treats the body's beta cells," Dr. Cohen says.
"In the past decade we've learned that DiaPep277 is not an invention, but a discovery. DiaPep277, in other words, is an important 'word' in the chemical dialog between the immune system and the tissues."
Wow, neat! (sometimes I just can't help myself).
Clinical trials have indeed shown the preservation of insulin production and improved blood glucose control. Studies were conducted in 40 medical centers in Europe, Israel and South Africa, including 457 newly diagnosed type 1 patients ages 16-45, randomized into two study groups. Patients in both groups used insulin, but patients in the treatment group were also injected with 1mg of DiaPep277 once every three months for two years. A1C levels in the DiaPep group were 7% and below, and insulin production was preserved after two years of treatment. (An extension study in Israel is being done over the next two years to test just how long patients will be able to produce insulin).
You might be wondering why it's so important for your body to keep secreting "some" insulin, if it's not enough do the whole job.
Dr. Dagan explained the long-term benefits: patients who are still able to produce their own insulin will have fewer blood glucose swings and are more likely to avoid complications. "This is not going to clear the disease. We are giving the opportunity to patients to maintain a quality of life," he says. "My own cautious hope is that our ability to arrest the autoimmune destruction of beta cells will turn out to be useful to patients with long-standing disease too, but only time will tell. When translating basic science to human application, one has to advance carefully one step at a time. The laboratory is not the bedside."
We appreciated his cautionary modesty, especially since earlier hype about the release of DiaPep277 went unfulfilled (it was initially planned for release in 2005). A second, global study is planned and should be completed by 2014. The company now hopes to get DiaPep277 to market by 2015 — a mere 10-year delay! Sheesh, science is glacial sometimes.
The Business Backstory
We also reached out to fellow D-blogger and industry watcher Scott Strumello, who's been following the business side of this development for several years — which is quite the tangled web of investment strategies:
"This is one of those treatments that have been tossed around like a hot potato for the past decade or more," Scott says. "For example, some rights to DiaPep277 were acquired by the company known as Aventis (which became Sanofi Aventis back in 1997), although full rights were reported to be acquired by the predecessor to today's Sanofi back in 2002, which then dumped the product in 2004."
"It kind of languished for several years until the rights were picked up by Andromeda Biotech in 2007. That company is a subsidiary of a specialized investment firm based in Israel known as Clal (which reportedly means 'inclusive' in Hebrew if my sources are correct)."
"Andromeda was convinced that DiaPep 277 still had sound business potential, and funded continued trials, albeit smaller sized trials. Clal then convinced drug giant Teva Pharmaceuticals to invest in DiaPep 277, and in 2009, Teva acquired the worldwide rights to market DiaPep277 if and when it is ever approved. Teva initially made a small investment, with options to expand its ownership stake contingent upon certain development hurdles being met, thus the latest announcement. Over the last few years, those development hurdles have apparently been met, hence Teva's investment in the product has grown over time."
Scott says the new CEO of Teva Jerry Levin, a South African native who attended Cambridge University and was credited with turning around a then-struggling Bristol Myers Squibb (BMS), is quite devoted to DiaPep 277's success, in the hopes of adding another notch in his so-called "string of pearls" strategy.
Even if this treatment languishes, but it increases the knowledge base on the autoimmune issue so that more and better treatments can move forward, then it's really accomplished something — and not just for investors.
Patience is something people with diabetes are all too familiar with. And scientists, too, of course.
I like how Dr. Cohen views the whole thing:
"What I do know is that it's most gratifying to see a lone observation materialize into something that might really help many people. How many medical scientists get to see such things? But the final steps are not in our power. The companies, the regulators, the lobby groups — all have to make it happen. I would certainly be delighted to see Teva and the other groups involved go all the way."
Us too, Dr. C.