Lilly’s Lantus Rival Sidelined By Safety Concerns
This article was originally published in Pharmaceutical Approvals Monthly
Executive Summary
Lilly will delay regulatory filing plans for its novel long-acting basal insulin peglispro (BIL) until at least after 2016 as it generates additional clinical data to better understand the effect on the liver.
Eli Lilly & Co. has lost out on its ambition to have a long-acting insulin on the market next year to go head-to-head against Sanofi’s blockbuster basal insulin Lantus (insulin glargine), now that the company is delaying regulatory filings for its long-acting basal insulin peglispro (BIL) in the U.S. and Europe due to safety concerns.
The company had been planning to file BIL in the first quarter of 2015 after announcing positive Phase III efficacy data last year. But Lilly has changed its tune, announcing Feb. 23 that the submission would be delayed indefinitely – and at least until after 2016 – while the company tries to better understand and characterize the drug’s effect on the liver. Additional clinical trial data are required, the firm said.
The latest announcement could signal the eventual demise of the program, given not only the regulatory issues it faces around safety, but the high commercial barriers a new novel insulin would have to overcome competing against a gold standard like Lantus with a solid safety track record.
Further impacting the market dynamics, biosimilar versions of insulin glargine are expected to reach the market in 2016 – with Lilly being one of the frontrunners to bring a biosimilar to market. Lilly and its partner Boehringer Ingelheim GMBH received tentative approval of their insulin glargine formula Basaglar from FDA in August, though an ongoing patent dispute has to be resolved before the product can launch (Also see "Time Ticks For Lantus With Tentative Approval Of Lilly/BI’s Basaglar" - Pink Sheet, 19 Aug, 2014.).
In Phase III trials testing BIL, the insulin showed superior reductions in blood sugar lowering compared to Lantus, but it also increased triglycerides and liver enzymes in some patients. Following the release of that data in May, investors and analysts have had a cautious view of the product, though Lilly defended the safety of the product.
“Lilly believes in the potential of BIL and its novel mechanism of action,” the company said in a statement. “The development of BIL remains important to us and we are committed to further evaluating the safety and efficacy of this investigational treatment for people with diabetes.”
The length of the delay hasn’t been determined and will depend on the clinical trial plans that are developed. The company is consulting with regulators to determine next steps.
Lantus is the top-selling insulin in the world, generating €6.34 billion ($7.19 billion) in 2014. Capturing even a small segment of the market would thus still represent a significant commercial opportunity. And Lilly has invested heavily in BIL to bring it through Phase III. The program enrolled more than 6,000 patients and included seven IMAGINE trials in patients with type 1 and type 2 diabetes.
Novo Nordisk AS’ once-daily basal insulin Tresiba (insulin degludec) was also delayed several years in 2013 after FDA requested the company run a cardiovascular outcomes trial (Also see "Novo Nordisk Dismayed By “Complete Response” Letter For Insulin Degludec" - Pink Sheet, 11 Feb, 2013.).
A Silver Lining For Basaglar?
With BIL tabled for now, the silver lining for Lilly could be the opportunity to focus on what may very well be the better commercial opportunity – Basaglar.
“With BIL essentially out of the picture, Lilly now has more pricing freedom with biosimilar Lantus as it will not have to worry about cannibalizing BIL sales,” Sanford Bernstein analyst Tim Anderson said in a same-day research note.
Lilly’s partner on Basaglar, Boehringer Ingelheim, might also appreciate the turn of events, given that Lilly wholly owns rights to BIL.
The most obvious commercial opportunity for a biosimilar is to price the drug below the originator product, but Lilly has not publicly talked about how it plans to price Basaglar. Many investors have believed Lilly has been unclear about its strategy around Basaglar for fear of undermining sales of BIL, Anderson said.
“We have generally thought that, of the two programs Lilly has in the long-acting basal insulin space, biosimilar Lantus is the more interesting opportunity,” he added. He forecasts 2020 sales of Lantus of $1.3 billion, which Lilly will share equally with Boehringer Ingelheim, versus BIL sales of $496 million.
A launch of the drug in U.S. before mid-2016 would require a court ruling opening the door up to earlier entry, however. Sanofi filed a patent infringement suit against Lilly in January 2014, triggering a 30-month stay of action, which would keep Basaglar off the market until mid-2016. The active ingredient patent protecting Lantus expires in February 2015, however. A trial in the case has been scheduled for September 2015.
Basaglar is generally considered a biosimilar of Lantus, but it was tentatively approved in the U.S. through the 505(b)(2) regulatory pathway, which allows drug makers to reference older small molecule drugs, rather than through the new pathway for biosimilars. Insulin products have been approved as NDAs, not BLAs for biologics, despite being considered a complex drug, thus leaving the 505(b)(2) pathway as an option for follow ons. In Europe, Basalgar was filed as a biosimilar.
Novartis AG’s Sandoz unit recently had the first approval under the dedicated 351(k) pathway, with the March 6 approval of Zarxio, its biosimilar of Amgen Inc.’s Neupogen (filgrastim) (Also see "Now Comes The Hard Part: Sandoz Must Sell Its Biosimilar" - Pink Sheet, 9 Mar, 2015.).