Iterum’s antibiotic is far from a Sure thing

Iterum should soon find out if it has an approvable asset in the antibiotic sulopenem, but even if the group succeeds it still has a hard road ahead.

It is a well-known fact that the world needs new antibiotics. But a lack of financial incentives means that companies in the space still have a hard time attracting investment and, ultimately, making a commercial success of their drugs.

This state of affairs has not put off Iterum Therapeutics, whose sole clinical asset, the antibiotic sulopenem, is in three pivotal trials which will soon yield data. But the company’s chief executive, Corey Fishman, admits that even if the results are positive cash could be a problem for the group.

Project Sulopenem
Company Iterum Therapeutics
Product NPV $439m
% of market cap 560%
Event Data from Sure 1, 2 and 3 trials
Due Q4 2019/Q1 2020

At the last count Iterum had $51m in the bank, which will only be enough to get it into 2020. Mr Fishman tells Vantage that, in the near term, the company will be looking for opportunities to raise more funds.

But he concedes that upcoming results from the Sure studies of sulopenem might not be a sufficient trigger for a public offering. “We hope positive data would lead to a reasonable reaction in the stock. But we don’t really count on that in this space – the market caps of all antibiotic companies have been beaten down.”

This is certainly true of Iterum, which has lost nearly two-thirds of its value since going public in May 2018. Mr Fishman says the group is prepared to be “creative” about funding, and is also considering debt and partnering sulopenem in “non-core” territories such as Asia or South America.

It’s complicated

Iterum believes it has a unique selling point: the company is gunning for the first approval for an oral penem, a class of antibiotic currently used for drug-resistant bacteria. Several penems are already on the market but all are given intravenously.

Sulopenem could have a couple of uses. Firstly it could be employed in a community setting like uncomplicated urinary tract infection (uUTI), where penems are not currently an option. Oral antibiotics of different classes are available but fluoroquinolones like ciprofloxacin are linked with resistance rates of up to 30%. In this setting, Iterum plans to focus its efforts on patients at a high risk of complications, such as the elderly or those with diabetes, if they have a bug that is resistant to therapy. 

Sulopenem’s second use could be as an IV-to-oral regimen in patients hospitalised for more serious infections who are currently treated with IV-only penem antibiotics. Currently, these patients have two options once the immediate crisis is over, neither of which is ideal: they can remain in hospital longer than strictly necessary to continue IV therapy, or can be discharged with an oral non-penem antibiotic, which again raises the issue of resistance.

Within these two markets, Iterum hopes to target around ten million patients in the US each year: around seven million in the community setting and the rest in hospital.

First, the company will have to show that its project is just as good as current antibiotic regimens, but without the problem of resistance. To this end, Iterum is running three pivotal trials of sulopenem in different settings, all designed to show non-inferiority to a relevant comparator on cure rates, defined as clinical response and the eradication of the pathogen in question.

Sure enough?

The first data, from the Sure 2 and 3 trials, both testing IV-to-oral sulopenem, are due in the fourth quarter of this year. Sure 2, in complicated urinary tract infections (cUTIs), pits the project against IV ertapenem followed by oral ciprofloxacin; while Sure 3, in complicated intra-abdominal infections (cIAIs) compares sulopenem with IV ertapenem followed by a combination of oral ciprofloxacin and metronidazole.

Sure 1 will be the last study to read out, in the first quarter of 2020. It is evaluating oral sulopenem versus oral ciprofloxacin in uUTIs. As well as aiming to show non-inferiority, the study also has a chance to show superiority in patients with resistance to ciprofloxacin.

Even if successful, Iterum might not have this niche to itself for long. Another oral penem, Spero Therapeutics’ SPR994, is currently in a phase III trial in cUTI, Adapt-PO, due to complete next year.

EvaluatePharma sellside consensus expects SPR994 to be the biggest-selling penem in 2024. The hope is that Spero’s project could help patients avoid hospitalisation completely, but Iterum’s Mr Fishman believes this might be a step too far for conservative doctors.

“If you’re sick enough to go into hospital, physicians might be uncomfortable about sending you straight home on an oral antibiotic,” he says. The chief exec adds that twice-daily oral sulopenem could have a convenience advantage over SPR994, which is given three times a day.

Still, in the already tough antibiotic space, Iterum could do without another reason for investors to be wary about its project’s chances on the market.

The penem antibiotic landscape
        Annual sales ($m)
Product Company Status Route of admin 2018 2024e
Orapenem/SPR994 Spero Therapeutics Phase III Oral - 371
Merrem (meropenem) Pfizer/Sumitomo Dainippon Pharma/Yuhan Approved in US in 1996 IV 329 341
Sulopenem Iterum Therapeutics Phase III IV and oral - 323*
Primaxin (imipenem) Merck & Co Approved in US in 1985 IV 265 181
Invanz (ertapenem) Merck & Co Approved in US in 2001 IV 496 97
*Includes both oral and IV sales forecasts. Source: EvaluatePharma.

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