Microbiome therapies are now one step closer to the clinic following the initiation of Seres Therapeutics’ Phase 3 clinical trial in patients with C. difficile infections.
According to a company statement, this will be the first pivotal trial for a microbiome-based therapy. It also triggers a $20 million milestone payment from its commercial partner Nestlé Health Science.
Seres has long been a leader in the high-buzz microbiome field. In June 2015, it executed the industry’s first-ever initial public offering (IPO), raising an impressive $134 million. It also claimed the ticker symbol MCRB.
But it’s not all fun and games being a biotech pioneer. MCRB shares fell off a cliff a year later, dropping from $36 apiece to just over $10. It came in response to a Phase 2 failure involving SER-109, the investigational drug candidate now being advanced into a Phase 3 trial.
Reiterating a statement released in January of this year, Seres’ Head of Investor Relations and Corporate Communications Carlo Tanzi said the issue with the 2016 study was two-fold; dosage and diagnostic criteria. This will be corrected in the Phase 3 trial by increasing the dose and using the C. difficile cytotoxin assay rather than PCR-based methods, which he said can be inaccurate.
Seres is optimistic that those hard-earned lessons and battle scars could ultimately help it succeed.
A Deep-dive Into Specialty Pharma
A specialty drug is a class of prescription medications used to treat complex, chronic or rare medical conditions. Although this classification was originally intended to define the treatment of rare, also termed “orphan” diseases, affecting fewer than 200,000 people in the US, more recently, specialty drugs have emerged as the cornerstone of treatment for chronic and complex diseases such as cancer, autoimmune conditions, diabetes, hepatitis C, and HIV/AIDS.
“Seres has the distinct and unique advantage of having completed several clinical microbiome studies (we are the only group to have these clinical data), and we have been able to learn a great deal from these efforts,” Tanzi wrote via email.
FDA has also stayed on board, helping Seres design the new Phase 3 study. Dubbed ECOSPOR III, it aims to enroll approximately 320 patients with recurrent C. difficile infections. Participants will be randomized 1:1 into either a control arm or an active arm that will be treated with SER-109. To best capture this population, the Cambridge, Massachusetts-based company expects to use more than 100 clinical trial sites throughout the U.S. and Canada.
Depending on the study results, Seres said the agency has indicated that ECOSPOR III could be enough to win a marketing approval. SER-109 has also scooped up breakthrough therapy and orphan drug designations.
In the United States, around half a million people are afflicted with Clostridium difficile each year. According to the CDC, people who have other illnesses or conditions requiring prolonged use of antibiotics, and the elderly, are at greater risk of acquiring this disease. The theory is that the antibiotics destroy the good bacteria in the gut, which would normally prevent C. difficile from taking hold. Different antibiotics can often beat back the infection. However, in around 20 percent of cases, C. difficile returns.
The good versus bad bacteria battle has made C. difficile one of the hottest targets for microbiome companies. While Seres is the most advanced, companies such University of Chicago spin-out Gusto Global, Finch Therapeutics, Immuron, Synthetic Biologics, and Rebiotix are also targeting the infection with various microbiota approaches. Next in line appears to be irritable bowel diseases (IBDs), such as ulcerative colitis and Crohn’s disease. As Tanzi noted, these conditions also have the most academic literature supporting them.
“As a company, we have prioritized clinical development efforts in diseases, including in C. diff infection and in ulcerative colitis, where the medical literature has demonstrated strong causative evidence showing that modification of the microbiome has resulted in improved clinical outcomes,” he said. “To date, this has been done primarily with fecal microbiota transplantation, an unapproved, burdensome and potentially unsafe procedure.”
It’s now up to Seres to provide an alternative.
Photo: spawns, Getty Images
