By Ruchi Jhonsa, Ph.D.
On 22nd October, Pfizer’s Hospital Business announced the acquisition of Arixa Pharmaceuticals, a company dedicated to developing next-generation antibiotics for drug-resistant gram-negative infections. This news comes just months after twenty of the world’s largest pharmaceutical companies, including Pfizer, announced creating a $1 billion fund to acquire or invest in small antibiotic companies and their nascent products that have been struggling to keep up amid a collapsing antibiotics industry.
Although the pact recently came into being, Pfizer was always keen on expanding in this direction, addressing the unmet need in the field. In 2016, the company acquired the US rights of AstraZeneca’s late-stage small molecule business of antibiotics that included EU approved drug Zavicefta (Avycaz in the US).
According to John Young, President, Pfizer Essential Health, “Pfizer is focusing on areas that further address global public health needs and that complement its core capabilities and experience in therapeutic areas, including anti-infectives. The company is committed to looking for ways to enhance its portfolio around the world where it offers patients and healthcare professionals access to more than 60 anti-infective and anti-fungal medicines.” The details of the new deal are still under wraps.
Arixa’s lead compound, ARX-1796, is an oral prodrug of Avibactam, which in combination with ceftazidime, got the USFDA approval in 2011. The combo drug is sold under the brand name Avycaz in the US. One might wonder why Pfizer would make a deal for the prodrug of a compound that it is already selling. Well, the reason is, Avycaz has poor bioavailability and hence works best when infused intravenously. This is an invasive method of drug delivery, which can also be inconvenient for patients and heavy on their pockets. ARX-1796, on the other hand, can be taken orally and is metabolized within the body to produce avibactam. According to the Arixa’s Co-Founder and CSO Dr. Eric M. Gordon, “The prodrug of avibactam was 60-80% absorbed when administered orally to humans.”
“Combined with an antibiotic such as ceftibuten, Arixa’s ARX-1796, if approved, opens the way for orally-available avibactam to be part of a next-generation, oral antibiotic combination for resistant urinary tract and other infections,” said Gordon.
“Through this acquisition, Pfizer will advance the development program for Arixa’s leading asset, ARX-1796. We are excited by the potential benefits ARX-1796 may provide to patients and the healthcare system overall, potentially allowing patients to leave the hospital earlier or avoid the need for hospital admission altogether,” said Annaliesa Anderson, Vice President, and Chief Scientific Officer Bacterial Vaccines and Hospital, Pfizer.
Why Do We Need Beta-Lactamase Inhibitors?
Common Gram-negative infections such as complicated urinary tract infections are becoming a major treatment challenge because of increasing rates of multidrug resistance.” However, since the first FDA approval granted to clavulanate, an oral treatment of gram-negative infections, in 1984, no new oral drugs have come into the market. Topping that, many bacteria have become resistant to clavulanate.
To solve this problem, Arixa Pharmaceuticals started developing antibacterials by modifying a class of beta-lactamase inhibitors called diazabicyclooctanes. This class of antibiotics suffers from poor absorption across the gut. However, if converted to the prodrug, noted Arixa’s co-founder, they can clear the gut barrier and get absorbed in the blood without problems. Following absorption, the prodrug structure self-cleaves itself, leaving the active compound behind. The active compound then blocks the enzymes made by the gram-negative bacteria that degrade beta-lactam antibiotics like ceftazidime.
“Common Gram-negative infections such as complicated urinary tract infections are becoming a major treatment challenge because of increasing rates of multidrug resistance,” said Jose Vazquez, M.D., Professor, Department of Medicine and Chief of Infectious Diseases at Medical College of Georgia at Augusta University. “There are a progressively larger number of patients who cannot be treated with oral antibiotics, and we are forced to treat them with intravenous agents. The option to administer an oral antibiotic containing avibactam to my patients with infections due to pathogens resistant to other oral agents, and thus avoiding intravenous administration and a hospital stay, would always be considered an important advance.”
“We are proud to have created and developed an important new drug candidate in a highly capital-efficient manner and believe Pfizer is the perfect company to take ARX-1796 into subsequent clinical trials and if approved, eventually to patients in need,” said John G. Freund MD MBA, Co-Founder, and CEO, Arixa.
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