Promising Phase III Data For Roche/Ipsen's Taspoglutide Heats Up GLP-1 Race

Once-weekly human GLP-1 analog taspoglutide shows superior HbA1c reduction to Byetta - and may soon catch Novo's liraglutide.

Roche and Ipsen's release of the first Phase III data for their human glucagon-like-peptide-1 analog taspoglutide may not have given more than a peek at top-line results, but it does showcase the changing dynamics of the GLP-1 development field - including the dosing and comparative data requirements that will be important to carving out a space in the market.

Roche and Ipsen announced the positive findings of the Phase III T-EMERGE 2 study Oct. 29, which showed the firms' once-weekly taspoglutide met the primary endpoint of non-inferiority to Eli Lilly/Amylin's marketed twice-daily GLP-1 analog exenatide ( Byetta ) and showed a superior reduction in HbA1c levels after 24 weeks of treatment.

Roche exercised its option to exclusive worldwide rights in 2006, after taspoglutide completed Phase II, for €56 million ($70 million) up front, in addition to a 2003 payment of €10 million and an agreement to fund the development costs.

Uncertainty In The Field Creates Opportunity

Taspoglutide has the potential to capture a significant share of the type 2 diabetes market, given delays to Novo Nordisk's competitor liraglutide. This once-daily drug, approved in the EU as Victoza in July 2009, was held up at FDA earlier this year following a split advisory committee vote in April over the relevance to humans of a pre-clinical thyroid cancer signal in rodents. Timing of the U.S. approval for liraglutide remains unclear; despite ongoing dialog with FDA, Novo has given no significant updates and re-iterated again during its third quarter results on Oct. 29 that formal FDA feedback is expected in the fourth quarter of this year (Also see "Novo Disappoints With No Liraglutide News, But Growth Is Strong" - Pink Sheet, 6 Aug, 2009.).

This uncertainty provides an opportunity for Roche and Ipsen. "It's like in a Formula One race, if the safety car comes on and holds everyone up, there's a chance for those behind to catch up," Roche's Investor Relations spokesman Karl Mahler said in an interview. A chance, but perhaps only a small one: Diabetic Investor's David Kliff cites sources as saying that FDA has basically approved Victoza and it's now down to label language.

Without specific data, it's difficult to assess the competitive prospects for taspoglutide as a later entrant in the GLP-1 class. Roche provided very little detail in the release on the Phase III T-EMERGE 2 study, and full data is unlikely to be made public before the next American Diabetes Association meeting in June 2010, according to Mahler.

The T-EMERGE 2 study is an open-label trial involving 1,189 patients, randomized into three active arms: taspoglutide 10 mg once weekly, taspoglutide 10 mg once-weekly titrated up to 20 mg once weekly after 4 weeks, and exenatide 10 mcg twice daily. The Roche/Ipsen drug was generally well-tolerated, although it shared the same nausea and vomiting-related side-effects as others in the class.

The study is the first of eight Phase III trials on taspoglutide, and the full program is designed to capture comparisons against a gamut of major brands in the type 2 market.

Roche's Mahler sounds bullish about the drug's prospects when describing the clinical trial program. "We're comparing the drug against a wider range of drugs than [those which] liraglutide" was compared against, he noted. Four of the eight studies within Roche's broader, 6,000-patient T-EMERGE program have active comparators, and these include Byetta, Sanofi Aventis' long-acting insulin glargine ( Lantus ), Merck's sitagliptin ( Januvia ) and Lilly/Takeda's pioglitazone ( Actos ). "In order to profile our drug as best-in-class, we have to compare it definitively against the standards-of-care," Mahler said. Those other trials should start reporting by the end of 2010.

Mahler also claims that Roche's filing will include not only full thyroid cancer data (tracked since Phase II) but also data to satisfy FDA's recently-amended cardiovascular risk-assessment guidelines for diabetes drugs (which were issued too late for Novo to fully adhere to). (See 'The Pink Sheet' DAILY, Jul 7, 2009).

Less Frequent Dosing - The Key To The GLP-1 Market?

Still, assuming equivalent or superior efficacy and safety (a big assumption at this point), a key differentiating factor for taspoglutide versus both Byetta and liraglutide is its less frequent dosing. Thanks to innovative formulation science developed by Ipsen, taspoglutide has intrinsic controlled-release properties which not only don't require a matrix, but also offer the potential for fortnightly administration.

In addition, taspoglutide's formulation allows the drug to be administered with a thinner gauge needle (and hence likely less painfully) than Lilly's next-in-line, once-weekly version of Byetta, Byetta LAR . This drug, another near the front of the race, will likely be a key player in the GLP-1 marketplace given Lilly's established franchise and presence with Byetta, LAR's advantageous dosing - and a PDUFA action date set for the first quarter of 2010. Lilly is heavily invested in the GLP-1 field, bringing another candidate up through the pipeline (Also see "Lilly Stands By Experimental Diabetes Drug, Despite Questions About Data" - Pink Sheet, 21 Oct, 2009.).

It's impossible to properly judge taspoglutide's prospects until full Phase III data are available. Meantime, Novo still has the advantage as far as GLP-1 newcomers go: its drug is already on the market and gaining share in the UK, Germany and Denmark. According to the figures presented by the Danish company in its Oct. 29 release, liraglutide has captured 40 percent of the GLP-1 market in Germany, at Byetta's expense. Analysts at Piper Jaffray aren't surprised; "this is in line with our view that there will be a rapid switch from Byetta to Victoza, driven by more patient-friendly dosing regime and lower nausea rates," they write in a same-day note.

Lazard's Terence Flynn also remarked on the Victoza share in European markets in his Oct. 29 note; Lazard anticipates either an outright approval or a "complete response" from FDA based on the advisory committee meeting and their conversations with companies and consultants. A Victoza approval could also be a sign of things to come for Byetta LAR, he suggested. "We continue to believe FDA approval of liraglutide bodes well for a future approval of LAR as it could partially remove the overhand created by the focus on thyroid cancer risk," he said. Lazard's forecast accounts for potential competition to LAR in the GLP-1 once-weekly landscape, and assumes Roche will file taspoglutide in 2010 with a launch in 2011.

For now, then, Novo is still firmly in the driving seat of Byetta-followers - but it's unclear how long it will remain there.

- Melanie Senior (m.senior @elsevier.com)