The 2008 Pipeline Report

Dec 01, 2008

This year's pipeline might be best remembered for drugs that evaporated at the last moment. Sanofi-Aventis gave up on Acomplia, one of the most celebrated drug candidates in the Pipeline Report for three years running, and took a whole crop of CB1 obesity drugs down with it. Flurizan, last year's headliner in Alzheimer's therapy, proved less than efficacious. And Prasugrel, once Eli Lilly's breathtaking balancing act of efficacy and safety, became the poster child for gridlock at FDA.

"It's grim," says Barbara Ryan, pharma analyst with Deutsche Bank. "There isn't a lot in late-stage development that we're really excited about."

But even in discouraging times, the academic, medical, and market experts who referee our drug candidates find compounds that promise therapeutic progress and even healthy profits. From the Factor Xa heart medications to new vaccines and cancer therapies, we take a look at 33 drugs that will matter in 2009 and beyond.

Asthma: chronic obstructive pulmonary disease (copd)

Paving the way for once-a-day

Novartis is poised to take a big piece of the market in chronic obstructive pulmonary disease (COPD) with its inhaled 24-hour bronchodilator indacaterol (QAB149), which will pave the way for new combination drugs that marry the new therapy with complementary compounds to create once-daily inhalants.

QMF149 will combine indacaterol with Asmanex (mometasone), a corticosteroid developed by Schering-Plough. The likely delivery device for once-daily dosage is S-P's Twisthaler, according to Adis R&D Insight.

Because the two long-acting compounds have different mechanisms of action, the combination therapy may result in greater efficacy.

"We see peak sales of $2.4 blllion in 2017 for QMF149," says Holger Rovini, a Datamonitor analyst in London. "GSK will no longer have the market to themselves." The drug's chief competitors are twice-daily inhalants, so the new drug is expected to have compliance advantages.

Rovini expects the second leading product in 2017 to be Novartis' long-acting single-dose inhalant QVA149 (indacaterol/glycopyrrolate), which will reach sales of nearly $1.9 billion worldwide. Datamonitor expects QVA149 to be particularly popular for the treatment of COPD patients.

Type 2 diabetes

Weekly dosing for GLP-1

In the treatment of type 2 diabetes, glucagon-like peptide-1 analogs—the class of drugs including Lilly/Amylin's Byetta (exenatide)—have a special place, according to Jay Skyler, MD, of the University of Miami's Miller School of Medicine. "GLP-1 therapy has the unique advantage of effective glucose control and concomitant weight loss," he says. "There appears also to be the potential for unique cardiovascular benefit." A crop of new once-a-week GLP-1 drugs promise to transform the class.

First up is a weekly formulation of Byetta, which as a twice-daily formulation remains a favorite among doctors and patients, despite persistent reports that it causes acute pancreatitis. A 30-week, open-label, non-inferiority Phase III study of 295 patients showed that once-weekly exenatide was more effective than twice-daily exenatide. But in early November, FDA rejected part of the data in the NDA having to do with equivalence, potentially delaying the drug's anticipated 2009 launch.

Taspoglutide, a human GLP-1 analog, has not been approved for daily use, and will begin its clinical life as a once- or twice-weekly treatment. Roche, which licensed rights to the drug everywhere but Japan and France, recently announced a Phase III study, triggering a €6.7 million milestone payment to Ipsen, which originated the compound and developed its excipient-free time-release mechanism. The study will enroll 990 patients with type 2 diabetes, and is scheduled to end in 2010.

The new drug liraglutide, from diabetes powerhouse Novo Nordisk, is being touted as the better Byetta. But to be approved, it first needs to satisfy FDA on pancreatitis. So says Les Funtleyder, healthcare strategist at Miller Tabak. FDA will see it as a class issue, even if Novo argues that diabetics just get more pancreatitis than the population as a whole. "If they have the pancreatitis data, fine," Funtleyder says. "If not, they'll have to get it."

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