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As anticipated, Roche’s (OTCQX:RHHBY) huge phase III taspoglutide clinical programme was a dominant feature at this year’s American Diabetes Association (ADA) conference. What was wholly unexpected, as recently as two weeks ago, was that the data would prompt speculation that the end is nigh for the product.

The fall from grace for taspoglutide, a drug earmarked as the fourth GLP-1 agonist to reach the market but forecast to be one of the most successful commercially, has been remarkably swift (see table below). A presentation to the financial community Monday night, when Roche confirmed that the hypersensitivity reactions were anaphylactic in nature, appears to have convinced many analysts that the chances of the drug reaching the market have fallen dramatically. Doctors at the ADA were more cautious in their conclusions, but it is hard to believe that taspoglutide is going to play as significant a role in the future GLP-1 market as previously thought.

Anaphylaxis concern

Aside from the adverse events, the efficacy of taspoglutide is actually looking very promising. In a series of studies from the T-emerge programme announced at ADA which pitted the drug against existing therapies, taspoglutide outperformed Lantus on glycaemic control, weight loss and hypoglycaemia, Januvia on glycaemic control and weight loss and glycaemic control against Byetta.

Unfortunately, it is the side effect profile that looks like scuppering this project, and the issues appear two-fold: initial tolerability and longer term hypersensitivity reactions.

Unexpectedly high gastrointestinal reactions, with particularly frequent occurrences of vomiting, have been seen. On the plus side, these have subsided after first administration and seem to only occur once.

As for the hypersensitivity reactions, these are much more concerning. Roche revealed Monday that the reactions have included tissue swelling, or angioedema, prolonged nausea and vomiting, breathlessness and changes in heart rate. Although all the patients recovered, worryingly most of these reactions occurred six months after treatment.

Citi analysts wrote Tuesday morning that although they have only been anaphylactic in nature, with no anaphylactic shock reported, such reactions are not tolerated in clinical practice at any frequency with such a chronic therapy.

And although Roche said these reactions occurred in less than 1% of patients, this refers to all 3,000 patients in the T-emerger programme. If only the patients exposed to the drug for more than six months are counted, this actually equates to an implied rate of closer to 2%.

Throw in the towel?

Roche has already announced that regulatory filings will be delayed by 12 to 18 months as it amends trial protocols to help identify patients with pre-specified anti-drug antibodies, which are thought to be linked to the reactions (Roche's diabetes blow prompts Amylin gain, June 18, 2010).

Unfortunately, the company does not know why these reactions are occurring, so it not only needs to find the route cause, it needs to work out whether the product can be amended to overcome these problems. The company has so far expressed its commitment to the project.

“I think it says how important this class is, the fact that they’re saying we’re going to figure this out because we have a good compound,” said Richard Bergenstal, president, medicine & science of the American Diabetes Association and a practicing endocrinologist who presented one of the papers on taspoglutide. “I think it says we think we can figure this out and get back on track and minimise the risk.”

However, most analysts seem to be of the opinion that Roche is more likely to throw in the towel at this point, rather than pushing on with a new formulation.

Regain rights

Clearly that will be disappointing for the Swiss pharma giant, which is trying to prove that it has blockbuster capabilities beyond its oncology stronghold. It is even more disappointing for Ipsen, the French drug developer that signed full rights to taspoglutide over to Roche back in 2006. The income from royalties, forecast at $122m by 2016, were viewed as crucially important for the company over the next few years.

Unfortunately, it seems highly possible that Ipsen may now regain rights to the project. Shares in the company have lost a quarter of their value since an inkling of the troubles ahead were glimpsed in abstracts released earlier in June; the stock fell a further 3% Tuesday, to a 14-month low of €25.45.

For the other players in the GLP-1 space, the market is starting to look a lot less crowded. Although the taspo news has already pushed back the launch date and hit sales forecasts for this product, in all likelihood the numbers in the table below are likely to shift further south in the coming months, to reflect this changing landscape.

GLP-1 agonists WW Annual Sales ($m)
Product Generic Name Company 2008 2010 2012 2014 2016 Status
Bydureon exenatide Amylin Pharmaceuticals (AMLN)/Eli Lilly (LLY) - 40 1,042 1,843 2,552 Filed
Victoza liraglutide Novo Nordisk (NVO) - 203 698 979 1,077 Marketed
RG1583 * taspoglutide Roche - - - 66 748 Phase III
Syncria albiglutide GlaxoSmithKline (GSK) - - 13 143 318 Phase III
Byetta exenatide Amylin Pharmaceuticals/Eli Lilly 775 749 317 214 175 Marketed

* forecast sales for taspoglutide have been moved back two years, from a launch in 2011 to 2013, and do not yet reflect new consensus to reflect the recent setbacks.

Source: EvaluatePharma

Source: Roche's Diabetes Dreams Fade as Taspo Data Deteriorates