Albiglutide Needs Greater Accuracy from Remaining Shots on Goal

November 18, 2011 Albiglutide needs greater accuracy from remaining shots on goal

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Victoza is looking increasingly bullet-proof. Novo Nordisk’s once-daily GLP-1 agonist proved superior to GlaxoSmithKline’s once-weekly version, albiglutide, in reducing blood glucose while also showing significant weight loss advantages in type II diabetics. This follows a similar win for Victoza against Amylin Pharmaceuticals’ once-weekly challenger in Bydureon (Amylin scores own goal in Bydureon vs Victoza head-to- head study, March 3, 2011).

Albiglutide still has a number of shots on goal – data this week from the Harmony 7 trial was the first from eight phase III studies all nearing completion – with a head-to-head against Merck & Co’s DPP-IV inhibitor Januvia probably the most significant in terms of determining albiglutide’s future role and potential in the diabetes market. Although expectations have never been that high, Glaxo’s product had an opportunity to capitalise on the setbacks to Byetta, Bydureon and Roche’s once-weekly taspoglutide – this first trial read out suggests that opportunity will be limited at best or missed altogether.

Playing catch up

Glaxo’s decision almost three years ago to embark on an extensive phase III programme for albiglutide, branded Syncria at the time, was seen as a bit of a gamble (Glaxo makes brave decision with phase III trials for Syncria, February 17, 2009).

Safety concerns about Amylin’s twice-daily Byetta, the only approved GLP-1 agonist at the time, and the fact albiglutide had a lot of ground to make up on Bydureon and taspoglutide, suggested an uphill struggle for Glaxo’s product which was licensed from Human Genome Sciences in 2004.

Although Bydureon has struggled to gain FDA approval – the regulator is due to make its latest ruling on the drug in January – and Roche has scrapped taspoglutide, Novo’s Victoza has stepped in and after a cautious start is rapidly gobbling up the GLP-1 market. Global sales of Victoza are expected to exceed $1bn this year compared to $657m for Byetta, despite Byetta’s four-year head start.

Meanwhile Sanofi and Zealand Pharma’s once-daily Lyxumia (lixisenatide) has made decent clinical progress. It was recently submitted to the European authorities and should be filed shortly with the FDA.

Come up short

As such, albiglutide could have done with a positive result in the ‘Harmony 7’ trial, the primary endpoint of which was to show non-inferiority to Victoza.

Unfortunately for Glaxo the 0.78% reduction in HbA1c – a marker of the amount of glucose in the blood – in patients receiving albiglutide failed to match the 0.99% reduction with Victoza.

Furthermore, on an increasingly important secondary measure of weight loss, albiglutide again came up short, its 0.62kg average reduction in weight significantly lower than the 2.21kg weight loss using Victoza. The case for Novo’s drug to eventually be used as an obesity treatment, in both diabetic and non-diabetic patients, appears to get stronger all the time.

The one positive to emerge from the trial was the safety data, with nausea and vomiting rates much lower in patients receiving albiglutide compared to those on Victoza (9.9% vs. 29.2% for nausea; 5% vs. 9.3% for vomiting).

Albiglutide’s miss on non-inferiority for efficacy but cleaner safety data is very similar to the outcome of Bydureon’s Duration-6 study against Victoza. What both these agents seem to gain in tolerability they give up in efficacy.

Further shots With nausea and vomiting side effects still a major barrier to using GLP-1 agonists for many patients and doctors, albiglutide’s once-weekly dosing and encouraging safety profile suggests a role may yet be found, most likely as a second-line therapy in this class.

As such, data from the ensuing seven pivotal trials, details of which are displayed in the table below, need to show albiglutide in a more favourable light.

Results from a trial using albiglutide in combination with Sanofi’s market-leading insulin product, Lantus, should be next, followed by the important head-to-head with Januvia. An open-label study directly comparing Glaxo’s product to Lantus should also be interesting, while the remainder of the trials mostly test albiglutide in combination with a range of standard diabetes treatments.

With around 4,900 patients involved in the Harmony programme, at an estimated cost of $75m, Glaxo is certainly giving albiglutide plenty of opportunity to prove itself. With initial results from most of these trials due over the next six months, the company will not have long to wait to see if the investment was worth it.

GlaxoSmithKline's 'Harmony' Phase III programme for albiglutide

Patient Start Completion NCT ID Notes Enrollment Date Date

May- NCT01128894 841 Compared to liraglutide (Victoza) - 'Harmony 7' Sep-11 10

Sep- NCT00976391 500 Combination with insulin glargine (Lantus) Oct-11 09

Compared to sitagliptin (Januvia) - in patients with May- NCT01098539 500 Aug-12 renal impairment 10

Jan- NCT00849017 309 Two doses compared to placebo Oct-12 09

Combination with pioglitazone (Actos), with or without Jan- NCT00849056 310 Oct-12 metformin 09

Combination with metformin, compared to sitagliptin Feb- NCT00838903 1000 (Januvia) + metformin / glimepiride + metformin / Dec-12 09 metformin alone

Feb- NCT00838916 779 Compared to insulin glargine (Lantus) Dec-12 09

Combination with metformin and glimepiride, Feb- NCT00839527 685 compared to metformin + glimepiride / metformin + Dec-12 09 glimepiride + pioglitazone

Total 4,924