Arsanis said today it has ended a Phase II trial for its sole clinical-phase candidate, ASN100, concluding that the monoclonal antibody combination would fail to prove its effectiveness in high-risk, mechanically ventilated patients with Staphylococcus aureus pneumonia.
The decision touched off a stock selloff that sent shares of Arsanis losing nearly three quarters of their value this morning in premarket trading. The share price plunged about 73%, from $18.19 at yesterday’s close of trading, to $4.95 as of 9:20 a.m.
Arsanis said its decision followed the recommendation of the trial’s independent data review committee, which determined that the study was not likely to meet its primary endpoint upon completion. The committee recommended that trial enrollment be discontinued.
The Phase II trial (NCT02940626) was a double-blind, placebo-controlled, superiority global study conducted at approximately 65 sites, and was designed to assess the efficacy and safety of ASN100 for the prevention of S. aureus pneumonia in high-risk, mechanically ventilated patients, an indication for which there are no approved therapies.
The trial had an estimated enrollment of 354 patients and an estimated primary completion date of October 8. The primary efficacy endpoint was the proportion of patients who develop S. aureus pneumonia through 21 days after dosing. The trial was designed to detect a 50% reduction in the occurrence of S. aureus pneumonia in the ASN100 arm when compared to placebo, Arsanis said.
Arsanis did not disclose trial data in its announcement.
“We intend to evaluate the complete dataset from the patients that were enrolled in the ASN100 study to better understand the basis for this result and expect to provide an update on the program following this review,” Arsanis president and CEO René Russo, PharmD, BCPS, said in a statement.
Arsanis said it intends to conduct follow-up visits on all patients dosed with ASN100 per the study protocol.
“We are disappointed that this clinical study was futile despite the survival benefit of ASN100 as compared to placebo observed in preclinical models of pneumonia,” Dr. Russo said. “However, Arsanis remains confident in the potential of monoclonal antibodies to prevent and treat serious infections, while also reducing the threat of antibiotic resistance.”
Monoclonal Antibody Combination
ASN100 is a combination of two co-administered fully human monoclonal antibodies, ASN-1 and ASN-2, which together neutralize the six cytotoxins critical to S. aureus pneumonia pathogenesis. ASN-1 neutralizes alpha-hemolysin (Hla), a cytotoxin that damages lung epithelial cells, and four leukocidins, cytotoxins that destroy human immune cells: gamma-hemolysin AB (HlgAB), gamma-hemolysin CB (HlgCB), Panton-Valentine leukocidin (PVL), and leukocidin ED (LukED). ASN-2 neutralizes the fifth leukocidin, LukGH, a particularly potent human cytotoxin also responsible for the destruction of human immune cells.
In December 2016, ASN100 was granted FDA Fast Track Designation for the S. aureus pneumonia indication.
Arsanis funded the development program for ASN100, ASN-1, and ASN-2—as well as a third monoclonal antibody, ASN-3—through proceeds from an $8 million purchase of company stock by the Bill and Melinda Gates Foundation in April 2017.
“At the request of the Gates Foundation, we will grant the Gates Foundation a nonexclusive, sublicensable license to any candidates or products developed under any of these programs, and all related technology necessary for the development, production and/or distribution or sale of the relevant product(s), for use in the prevention of neonatal sepsis caused by S. aureus and/or other bacterial pathogens,” Arsanis disclosed in its Form 10-K Annual Report for 2017, filed March 9.
The Gates Foundation investment came two months after Arsanis won a $9.3 million grant from the foundation in return for the company advancing through to Investigational New Drug (IND) filing an initial candidate from a panel of respiratory syncytial virus (RSV)-targeting antibodies for which Arsanis gave the foundation an exclusive global license.
Dr. Russo said Arsanis will shift its focus and resources to other development programs, including the development of ASN500 for the prevention of RSV infection. The company cited positive preclinical data for ASN500 showing the monoclonal antibody offered high potency and the potential to better serve new and existing target patient populations than existing therapies through its dosing strategy, manufacturing and route of administration.
Arsanis expects to advance ASN500 into Phase I clinical trials in 2019, Dr. Russo added.
The company has two additional preclinical candidates, both monoclonal antibodies—ASN300, indicated for prevention and treatment of Klebsiella pneumoniae bacterial infections; and ASN200, indicated for prevention and treatment of Escherichia coli bacterial infections.