The financiers who have backed Intarcia Therapeutics to the tune of $400m over the past couple of years are no doubt breathing a sigh of relief now that two of the four trials necessary to gain regulatory approval of its exenatide-secreting implant ITCA 650 have reported positive data.
With two phase III trials ongoing the group has about eight months of funding left – not enough to get it through regulatory filing in diabetes, says its chief executive, Kurt Graves; but this was in the plan all along. “We knew if we achieved success in phase III we would have multiple new avenues to capital on better terms,” he tells EP Vantage. “We turned over two really positive phase III cards. We now have a lot of other options.”
The intention is to secure a partner for ITCA 650 rather than seek a wider investor pool via an initial public offering – the latter option being a very popular one this year. “We’re IPO-ready if we wanted to. We’re not planning to do it in the near future,” Mr Graves says.
“We’ve always been planning on having at a minimum a major partnership outside the US and have always been planning at a minimum to keep full control of the product and our technology in the US.”
Diabetes is a space dominated by three names – Lilly, Novo Nordisk and Sanofi – so these would be natural partners, although Mr Graves did not discuss what companies he has been speaking with.
ITCA 650 is a small implant the size of the matchstick inserted under the skin of the abdomen. A pump driven by osmotic pressure slowly drives exenatide, the active ingredient of AstraZeneca’s Bydureon, into the bloodstream to help control blood sugar. Patients get a steady dose of the GLP-1 receptor agonist over up to 12 months, as opposed to the weekly injections of Bydureon or the daily ones of its big rival, Novo Nordisk’s Victoza.
The two phase III trials that reported this week are against placebo. In the 460-patient Freedom-1, patients unable to achieve glycaemic control on oral medications like metformin or sulfonylureas were treated with ITCA 650 for nine months, with change in blood sugar the primary endpoint. In the 100-patient Freedom-1 HBL study patients with high blood sugar at baseline, measuring between 10% and 12% on the HbA1C measure, received the same treatment.
Detailed data are being held back for next year’s ADA meeting in Boston, but Intarcia did report that Freedom-1 showed the implant to be significantly superior to placebo for two doses, 40mcg and 60mcg. The high-baseline study showed a mean HbA1C reduction of 3.4 points, from a mean baseline of 10.8%, and 25% of patients got their blood sugar down below the goal of 7%.
Significantly, nausea rates and discontinuation from nausea were reported to be in the low single digits. This has been the side effect that has caused the biggest problems for the GLP-1 class, with nausea rates in the mid-20% or higher for Bydureon and Victoza.
“Whenever you inject, we know that some of the nausea and GI side effects you can get are from the [pharmacokinetic] spikes. Obviously our delivery system avoids those spikes,” Mr Graves says.
The remaining efficacy trial is a 500-patient head-to-head test against Merck & Co’s Januvia, the biggest-selling oral diabetes drug, which is due to read out in August 2015. Finally, a 4,000-patient cardiovascular outcomes trial will continue through 2018; interim data is expected to be the last component of ITCA 650’s regulatory filing, which Mr Graves expects to submit in late 2015 or early 2016.
New sales strategy
Of course, selling an implant will be a different commercial proposition than selling an injection pen or a pill, something Mr Graves recognises. While it will be regulated as a drug rather than as a device, ITCA 650 will require specialised marketing that will need to apply the strategic approaches of device companies, and one that could potentially limit its appeal to the primary care doctors now prescribing oral antidiabetics, Bydureon and Victoza.
Selling those general practitioners on the implant will be essential to fulfilling ITCA 650’s promise. Mr Graves believes that GLP-1s are underused because they are injected and because of their well-known tolerability issues, creating a limited market to which pharma companies have responded by selling at a higher price.
“We have an opportunity to change that complete dynamic and move GLP-1s [to an early treatment line] because we’re not an injectable,” he says. “When we can go to a far bigger market we can price ourselves like an oral medicine and have access to a bigger volume of patients.”
The size and scope of any deal will show whether the diabetes players agree with Mr Graves' prognosis.