None were there. The FDA has pinned "breakthrough" status this year on more than a dozen drugs, mostly for cancer and rare diseases. Diabetes therapies have been absent from the mix so far, and it could be a long time before they join the breakthrough club, where hotshot drug candidates get their wings to fly through development and reviews.
The lack of breakthroughs in the diabetes field is noteworthy for a few reasons. It shows some of the key differences between diabetes drug development and R&D in other fields such as oncology and infectious diseases. It also underscores the high level of caution in both how regulators regulate diabetes drugs and developers develop them. In this cautious environment, none of the Phase III experimental drugs in the ADA spotlight were for first-in-class treatments.
But breakthroughs are needed. The world faces a major health crisis with the global population of diabetics expected to explode from more than 370 million in 2012 to well over half a billion by 2030, according to the International Diabetes Federation. These will mostly be patients with Type 2 diabetes, a disease that hampers the body's ability to produce ample insulin or drives resistance to insulin, which is a hormone that the body uses to convert glucose into energy, according to the ADA.
To date, pharma companies have been rewarded handsomely for improving on existing therapies, spending the majority of their R&D dollars on such treatments. More than 90 years since the discovery of insulin, for example, 6 of the top 10 biggest selling drugs for diabetes are forms of insulin led by Sanofi's ($SNY) Lantus, which raked in 2012 revenue of $6.5 billion, according data from EvaluatePharma. And all the top insulin companies have new insulin therapies in their experimental drug pipelines. Why wouldn't they?
"Drugmakers are unlikely to pursue anti-diabetics and particularly new and innovative therapeutics unless they believe that their drug is going to be a true blockbuster," says Lou Tartaglia, a metabolic drug expert and partner at Third Rock Ventures, "because they know that they're going to have to do very large clinical trials in order to market their drug and they're going to have to likely take on very significant cardiovascular outcome trials to prove beyond a shadow of a doubt that their drug does not increase cardiovascular risk."
Take Novo Nordisk's ($NVO) Tresiba, a long-acting insulin for which the FDA denied approval in February because it wanted more data on cardiovascular outcomes, meaning the therapy would be sidelined from the U.S. market for years.
Since 2000, the FDA has stamped approvals on just 13 new drugs for diabetes, compared with well more than 60 new cancer meds and nearly as many drugs for infectious diseases, according to an analysis from Bernard Munos, who is founder of a consulting group called the InnoThink Center for Research in Biomedical Innovation in Indianapolis. Check out Munos's data and decide whether most of these drugs are innovative:
- 13 drugs
- 4 first-in class (Symlin, Byetta, Januvia, Invokana)
- 4 insulins (Lantus, 2000; Novolog, 2000; Apidra, 2004; Levemir, 2005)
- 2 GLP-1 agonists (Byetta, 2005; Victoza, 2010)
- 4 DPP-4 (Januvia, 2006; Onglyza, 2009; Tradjenta, 2011, Nesina, 2013)
- 1 SGLT2 (Invokana, 2013)
- 1 insulin secretagogue (Starlix, 2000)
- 1 synthetic amylin analog (Symlin, 2005)
These data points show that less than a third or 29% of FDA-approved treatments for diabetes over the past 12.5 years were first-in-class therapies, while others could be called me-too drugs. This percentage is likely to decline over the next year, with Sanofi, GlaxoSmithKline ($GSK) and probably Eli Lilly seeking FDA approvals for their own drugs in the GLP-1 class. Also, there are several more SGLT2 inhibitors in late-stage development.
Yet give some credit to pharma researchers who have made advances over the decades in treating diabetes, which is a manageable chronic illness with a variety of medical options to keep patients leading productive lives. Cancer, conversely, is the second-leading killer of Americans, according to the Centers for Diseases Control and Prevention (CDC). Pharma leaders can only dream of turning aggressive malignancies into manageable illness like diabetes.
In just a cursory look around the diabetes field, breakthroughs seem like they could be on their way.
|Lou Tartaglia, interim CEO of Ember Therapeutics--Courtesy of Third Rock Ventures|
Third Rock's Tartaglia is interim CEO of Watertown, MA-based Ember Therapeutics (a 2012 Fierce 15 company), which is targeting brown fat cells as novel approach to treating obesity and diabetes. Its programs are in pre-clinical development.
Nimbus Discovery, another venture-backed biotech in the Boston area, has ambitions to enter the clinic with a novel drug for diabetes and fatty liver diseases. By targeting Acetyl CoA Carboxylase (ACC), Nimbus' preclinical candidate ND-630 cut body fat markers and triglycerides while improving insulin sensitivity in obese mice.
On Big Pharma side, Johnson & Johnson ($JNJ) has rights to develop drugs that target betatrophin, a hormone that Harvard researchers showed could trigger dramatic increases in the production of insulin-making beta cells in mice. This area could blossom with powerful new drugs for diabetics, including patients with Type 1 diabetes whose bodies don't produce insulin.
In a small human study, Isis Pharmaceuticals ($ISIS) showed some dramatic decreases in triglycerides and increases in good cholesterol for patients with Type 2 diabetes on its ISIS-APOCIII Rx candidate at the ADA meeting.
"There's a lot of activity in pre-clinical research that I think will come to fruition and make a big difference," Tartaglia says. "So scientifically I think we're looking for some true breakthroughs."
True, breakthroughs are on their way. But don't expect them to arrive any day soon.
-- Ryan McBride (email | Twitter)