The diabetes battle: Will Novo’s oral GLP-1 knock Trulicity off its perch?

December 11, 2018 | Company

Melanie senior

Timing is of the essence for Novo Nordisk. The Danish company may use its priority review voucher to accelerate oral GLP-1 agonist candidate, semaglutide, past the regulators – though a decision is not confirmed. Buying a few more weeks – or months – to eat into sales of Lilly’s fast-growing once-weekly injectable GLP-1, Trulicity, would make sense. That drug is already head-to-head in market share terms with Novo’s pioneer once-daily injectable GLP-1, Victoza. And in November 2018, Lilly played a new trump card: superior cardiovascular outcomes data, versus placebo, for Trulicity in the 9,900-patient REWIND trial. Uniquely, according to Lilly, two thirds of the patients included in the trial did not have heart disease to begin with. The 5-year median follow up period is also the longest in any GLP-1 study, the company claims.

Novo has already launched its own once-weekly contender to rival Trulicity. Ozempic (injectable semaglutide) was approved in late 2017 in the US, with trial evidence suggesting it may lower blood sugar and promote weight loss to a greater extent than Trulicity. The Danish company has been working hard to try to claw back some of Lilly’s gains, but Trulicity’s $2 billion 2017 sales still dwarf young Ozempic’s (though Victoza is still category leader, selling $3.5 billion in 2017).

Novo’s once-daily pill version of Ozempic won’t be available before the end of 2019 – even with the priority review. But if approved, it could help Novo shore up its leadership of the GLP-1 space. And that is the most important battlefield in diabetes right now. These biological drugs lower blood sugar by stimulating insulin release and inducing satiety. They can help delay patients’ progression onto injected insulin, and, crucially, they are much easier to use than insulin. They are taken as a standard dose, without the requirement to measure blood sugar levels. That matters a lot, since adherence is the key challenge in diabetes: the drugs work perfectly well in controlled trials, but have proven far harder to use effectively in the real world. GLP-1s are more valuable commercially, too, as insulin prices continue to be eroded by competitive pressures, including from biosimilars. GLP-1 drugs will account for the largest chunk of diabetes drugs’ sales by 2024, according to analysts.

GLP-1 agonists have already evolved from twice- and once-daily to once-weekly injections, ramping up billions in sales in the process. By creating an oral version – one of the first oral

formulations of a biologic drug – Novo could hit another jackpot, if patients find it easier to take than a weekly injection.

There is an ‘if’. Most people would prefer to avoid needles. But swallowing oral semaglutide does require some fore-thought. The drug must be taken on an empty stomach, with water (but not too much), and at least 30 minutes prior to a meal. Otherwise, it may not work properly. As David Kliff, publisher of Diabetic Investor, notes, these constraints “add an element of uncertainty” to a drug that most analysts believe will be a sure win.

There will be a pricing battle, too. If Novo prices oral semaglutide like a pill, it might gain market share but risks accelerating price declines for injectable GLP-1s, including its own Ozempic. Either way, Lilly will push Trulicity’s cardiovascular data hard. (Oral semaglutide narrowly missed showing a statistically significant reduction in major adverse cardiovascular events versus placebo, in the last of ten trials supporting its efficacy and safety. It did show a statistically significant reduction in all-cause mortality among the approximately 3000 patients with high CV risk, however.)

Kliff reckons there may, by late 2019, be another game in town: Intarcia Therapeutics’ GLP-1-releasing implant. No pills, no injections, just a match-stick-sized device inserted under the skin of the abdomen, changed every six months. But FDA rebuffed the exenatide micropump in late 2017, prompting staff cuts and a long silence from the company.

If and when Novo’s oral GLP-1 is approved, it may bump up against another highly competitive class of oral diabetes drugs: SGLT-2 inhibitors. These are locked in their own battle for market share as sponsors push data showing the treatments may help reduce the risk of cardiovascular and kidney disease.

The diabetes drug market will remain dynamic, as incumbents battle it out using pricing and convenience to secure optimal market access.