AM-Pharma still on track with sepsis drug despite mixed phase 2 readout

The pharma industry doesn’t have a strong record when it comes to trying to find treatments for sepsis, but AM-Pharma has today reported what looks like a rare win.

The Dutch biotech has just reported a greater than 40% reduction in mortality for its recombinant form of the enzyme alkaline phosphatase (recAP) compared to placebo in sepsis-related acute kidney injury (AKI). Kidney damage is a common early consequence of the havoc that results from the overblown immune response to infection that occurs in sepsis patients.

AM-Pharma’s CEO Erik van den Berg told FierceBiotech that the intention now is to move the program into a phase 3 study in consultation with clinical investigators, regulators and, of course, Pfizer, which took out an option on the company back in 2015.

In the trial, recAP—which has a fast-track designation from the FDA—was compared to placebo on top of standard therapy with antibiotics—still the primary treatment option for sepsis patients along with supportive care.

The data isn’t a home run. The study in 301 patients—called STOP-AKI—missed its primary endpoint of showing an improvement in kidney function in the first week. However, it did show a “significant, progressive and sustained improvement” in renal function over the 28-day study period, without any major toxicity issues.

Nevertheless, the mortality reduction coupled with renal function data suggests that the program remains on track in an indication that analysts have suggested could deliver blockbuster sales for a safe and effective product.

Van den Berg said that the study “missed its primary endpoint … it met the primary objective of showing recAP could ameliorate kidney damage,” adding that it is actually more important to have demonstrated an impact of the drug on a hard clinical endpoint such as survival.

“The data is directive of the way we should go with recAP” in pivotal testing, he said, and the company will now spend a few months discussing a phase 3 protocol in sepsis-related AKI, as well as its plans in AKI resulting from other causes and inflammatory bowel disease, another key target for the drug.

The positive phase 2 data put sepsis-related AKI at the top of the priority list, he suggested. If confirmed in further trials, the drug could be a big step forward in hospital-acquired AKI, which affects around three million patients in Europe, the U.S. and Japan every year and kills roughly 700,000 patients.

Past efforts to develop a drug for sepsis or related conditions have almost entirely ended in failure. Way back in the 1990s, Centocor’s Centoxin and Xoma’s E5 were the first high-profile casualties, while more recent failed programs include Eisai’s eritoran, Agennix’s talactoferrin and AstraZeneca/BTG’s CytoFab, which all failed in late-stage testing.

Meanwhile, the only drug approved for sepsis to date—Eli Lilly’s Xigris (drotrecogin alfa)—was withdrawn after postmarketing studies showed it actually had little benefit. Xigris never achieved the sales projected on its approval in 2001 with sales of around $1.5 billion over its 10-year spell on the market.

“We are delighted with the outcomes of our STOP-AKI Phase 2 study,” said van den Berg. “This is a major advance in the development of recAP, which could have a significant impact on patients with AKI, for whom there is currently no treatment available.”

The results of the study are being presented today by principle investigator Peter Pickkers, M.D., Ph.D., of Radboud University Medical Center at the AKI & CRRT 2018 conference in San Diego.