Intra-abdominal infections (IAIs) are commonly occurring surgical and clinical emergencies that are major contributors to non-trauma deaths in the emergency room. Complicated intra-abdominal infections (cIAIs) are those that extend into the peritoneal space in the abdominal cavity as a result of perforation or other damage to the gastrointestinal tract. Infections categorized as complicated include intra-abdominal abscess, stomach or intestinal perforation, peritonitis, appendicitis, cholecystitis or diverticulitis. These cIAIs are a major cause of morbidity and mortality, particularly if poorly managed. In a worldwide observational study conducted in 4,553 patients with cIAIs in 132 medical institutions during a 4-month period from October 2014 to February 2015, the mortality rate was 9.2%, or 416 patients.
Different bacteria are responsible for cIAIs, including Gram-negative aerobic bacteria, Gram-positive bacteria and anaerobic bacteria. Early detection, containment and appropriate antimicrobial treatment are essential to successful treatment, made even more critical with increasing rates of infections caused by drug-resistant bacteria, which limit the effectiveness of currently available antibiotics.
We are thrilled to have received FDA approval, and a positive opinion from the Committee for Medicinal Products for Human Use (CHMP) in Europe all within the same quarter. Each milestone is a significant accomplishment on its own and achieving both underscores the potential for Tetraphase and the medical need for XERAVA. We will now turn our efforts towards delivering XERAVA to patients suffering from cIAI in the United States, an important goal we expect to begin executing on in the fourth quarter of this year. We look forward to a successful launch and commercialization moving forward.
– Guy Macdonald, President and CEO, Tetraphase Pharmaceuticals
Tetraphase’s antibiotics platform is based on the core chemical structure of tetracycline, to which the company has applied its fully synthetic chemistry technology to drive discovery and development of innovative and potent antibiotics with unique profiles. This technological approach, which was pioneered at Harvard, has been used by Tetraphase to synthesize and test more than 3,000 new tetracycline derivatives, resulting in a pipeline of novel tetracycline antibiotics.
Source: Tetraphase Pharmaceuticals
Validation for Tetraphase
Investors in Tetraphase have had a volatile run since the company went public in 2013 at $7.00 per share. The stock had a dramatic rally beginning in mid 2014 and peaking in July 2015 at $52.53 on the promise of eravacycline, but the bubble burst in September 2015, however, in the wake of poor results from a Phase 3 trial in complicated urinary tract infections. The stock lost 79% of its value that day, and, after a modest recovery in early 2017, got hit again in February 2018 when the drug candidate failed to meet primary endpoints in a separate Phase 3 trial.
The approval yesterday by the FDA of Tetraphase’s drug in cIAI represents a validation of the science and is further notable given that Big Pharma, as Saumya Joseph and Tamara Mathias wrote for Reuters, has been “shying away from developing antibiotics, as combating resistant ‘superbugs’ become increasingly challenging. AstraZeneca Plc and Novartis AG have exited the space, and earlier this year Allergan Plc said it was planning to sell its infectious disease unit, which includes antibiotic treatments.”
Today’s FDA approval of XERAVA provides a new weapon in the battle against antibiotic resistance and addresses an unmet medical need for patients suffering from multi-drug resistant infections and other serious infections. We are pleased to have provided support to Tetraphase since 2012, through its collaboration with CUBRC [Calspan-University at Buffalo Research Center], to develop this new antibiotic treatment. The drug’s approval underscores the value of public-private partnerships in addressing global health threats and the challenge of antibiotic resistance.
– Rick A. Bright PhD, Director of the Biomedical Advanced Research and Development Authority (BARDA).
A new option for physicians
Tetraphase Chief Medical Officer Larry Edwards, on the conference call yesterday discussing the approval, said that the target price for XERAVA would be “$175 to $250” per day for XERAVA. Mr. Edwards also shared some feedback from physicians: “This is a drug that gives us the broad spectrum coverage that we need and potentially doesn’t put my patient at risk of having C. diff.” Clostridium difficile, or C. diff, is a bacterium that can cause severe symptoms ranging from diarrhea to life-threatening colon inflammation. XERAVA is “highly potent in vitro against C. diff,” according to Mr. Edwards.
Reuters noted that “other recently-approved antibiotics used as a last line of treatment are priced at nearly $1,000 per day,” and CEO Guy Macdonald said, “We’re trying to price XERAVA at the lower end, so that patients can get access to the product when they need it in first or second line therapy.” Reuters cited H.C. Wainwright analyst Ed Arce’s estimates that XERAVA will generate peak sales of $340 million in the US and EU in 2027.
Complicated intra-abdominal infections are the second-most prevalent infection site in intensive care units (ICUs), as well as the second leading cause of infection-related mortality in ICUs. With the growing crisis of antibiotic resistance, treatment options for these polymicrobial infections are limited following surgery or percutaneous drainage, and the causative pathogens may be multi-drug resistant. Current empiric treatments for cIAI have limitations, and there is a need for new and novel treatments. Eravacycline has a broad spectrum of antibacterial activity and a clinical profile that addresses this unmet medical need.
Eravacycline also has a favorable safety profile as observed in clinical trials, and no dose adjustment is required when given to patients with renal impairment, which is advantageous for seriously ill patients who may have impaired kidney function. Additionally, the drug may be given safely to patients who are allergic to penicillin. This new and novel treatment may be of great benefit to patients with complicated intra-abdominal infections.
– Philip S. Barie, MD, Professor of Surgery and Professor of Public Health in Medicine at Weill Cornell Medicine, and an attending surgeon at New York-Presbyterian/Weill Cornell Medical Center.
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