Pharm Exec's 2012 Pipeline Report - Pharmaceutical Executive


Pharm Exec's 2012 Pipeline Report

Pharmaceutical Executive

Diabetes: Added Value

While some believe that FDA has been "overly judicious on compounds for diabetes and other metabolic syndromes," as Matthew Geller, president and founder of Geller Biopharm tells it, there is still a lot going on. After all, the global diabetes market is the fourth-largest, at $34.4 billion in 2010, a 12 percent increase over 2009, according to IMS data. The next possible blockbuster to enter the market may be a GLP-1 from Amylin/Alkermes called Bydureon. The drug worried investors last March after a study showed an efficacy rate slightly below Novo Nordisk's Victoza, a GLP-1 that launched in 2010; although the differentiating factor is Bydureon's once-a-week dosage, compared with Victoza once-a-day and Amylin's Byetta twice-a-day. "People will always prefer the less frequent dosing," says Ben Weintraub. "The reason we like the GLP-1 mechanism of action is that, in addition to glucose control, it helps patients lose weight, and has other ancillary benefits, like bringing down LDL levels and blood pressure."

Lilly backed out of its partnership on Bydureon, after months of bickering (and a lawsuit from Amylin) over Lilly's surprise collaboration with Boehringer Ingelheim to promote other type 2 diabetes drugs, including Tradjenta, an oral DDP-4 inhibitor. Amylin said Tradjenta is a direct competitor of Bydureon, which would create obvious promotional problems. The eventual breakup could be positive for Amylin, according to at least one analyst—Thomas Russo at Robert W. Baird & Co., who upgraded Amylin shares from neutral to outperform post-breakup. Russo told Bloomberg[ital.] that he expects Bydureon to gain approval in January 2012 (the PDUFA date is January 28, 2012), and that Amylin had become an acquisition target after the lawsuit emerged; now the company is free to make a deal. Bydureon was approved in the EU in June.

Novo Nordisk, the insulin Hercules, may receive an FDA approval for its insulin degludec product next year as well; the company submitted an NDA for Degludec and DegludecPlus (ultra-long-acting basil insulin plus a bolis boost of insulin apart) to FDA and EMA in September, and is subsequently in preregistration for both types of diabetes. Degludec is a thrice-weekly formulation, or once every 40 hours. Mads Krogsgaard Thomsen, executive vice president and chief science officer at Novo Nordisk, said on a Q2 earnings call that the company will "seek label flexibility for any time of day, enhancing convenience and potentially treatment compliance." Thomsen told Dow Jones that he expects both to be blockbusters. Meekings was slightly less convinced: "Obviously, there's some benefit [with the dosage], but realistically, I think it will probably be used as a once-daily regimen—prescribers are likely to be wary of weekend dips in glycemic control. That doesn't really differentiate it that much from what's already out there ... It will definitely be a great drug, but how great is the question?" Thomson Reuters forecasts sales of Degludec at $1.5 billion by 2016. On the other hand, "How much more [are patients] willing to pay for ultra-long-acting insulin? ... In a few years we'll have biosimilar insulin, and that will make it even more difficult for new formulations like Degludec to actually get taken up," says Weintraub. "We have pretty modest expectations."

Coming in around the same time as Bydureon is the first of a new—and long-anticipated—class of anti-diabetic drugs, known as sodium-glucose co-transporter 2 protein inhibitors. At the Cleveland Clinic Innovations Summit in October, SGLT2s were named one of the top 10 medical innovations for 2012. The SGLT2s represent "a paradigm shift in diabetes treatment, because they reduce blood sugar in a totally new way: by causing it to be excreted during urination," the Cleveland Clinic said in a writeup of the class. The SGLT2s could also contribute to weight loss, since "so many calories would now be lost during urination."

The closest SGLT2 to market—Bristol-Myers Squibb's and AstraZeneca's dapagliflozin—could be approved as early as the first quarter of 2012, despite the fact that safety concerns, including a small but significant incidence of bladder and breast cancer, gave the FDA pause in late October. Dapagliflozin now shares a PDUFA date with Bydureon, on January 28, 2012. AZ and BMS are in Phase III with a fixed combination of dapagliflozin and metformin for type 2 diabetes. Although the drug is expected to emerge as a post-metformin treatment, the combination "might have huge sales potential if it shows efficacy" in the combo, says Meekings. Thompson Reuters predicts relatively modest sales for dapagliflozin - $403 million in 2016—while Adis R&D Insight has the drug reaching blockbuster status by 2015.

The other SGLT2, originated by Mitsubishi Tanabe Pharma and Tanabe Seiyaku, and licensed worldwide by Johnson & Johnson, is currently in Phase III. The drug is called canagliflozin, and it's also being tested in combination with metformin. J&J has said it expects to file for type 2 "between 2011 and 2015." Adis R&D Insight is less bullish on canagliflozin, with a prediction of $421 million in sales by 2015. The firm doesn't show any revenue for canagliflozin before 2014. We'll find out next year if more, or "ultra" dosages can add enough value to bring in patients and payers.


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