Seres And Ferring Go Head-To-Head In Recurrent C. Difficile Market
Two New Microbiome Medicines Launched In 2023
Executive Summary
After the historic approvals of Seres’ and Ferring’s microbiome-based treatments for recurrent Clostridioides difficile infection, the two companies are waiting to see who dominates the $1bn market. Physicians say patients will steer the choice of treatments.
For patients in the US with recurrent Clostridioides difficile infection (rCDI), the recent approval of two safe and effective treatments is a win. Now the question for Seres Therapeutics, Inc. and Ferring Pharmaceuticals is whether either will be able to dominate the market.
Rebyota (fecal microbiota, live – jslm) was approved by the US Food and Drug Administration in November 2022 and Vowst (fecal microbiota spores, live-brpk) received the regulator's nod just a few months later, in April 2023. Both are indicated for the prevention of rCDI in adults after antibiotic treatment for an initial recurrence. Arguably the greatest differentiator between the two is their mode of administration: Rebyota is instilled as a one-time enema, while Vowst is taken as four capsules daily for three days.
“You would think 100 out of 100 patients would pick capsules, but that's not the case,” Jessica Allegretti, associate professor of medicine, Harvard Medical School, told In Vivo. “Some people don't like taking pills. Some people want you to do the work for them. And depending on the age of the patient, how sick they are and whether they have any swallowing issues, for example, rectal administration may be more attractive.”
Roughly 500,000 people in the US develop CDI every year, approximately 30,000 die from the infection, and the illness exacts an annual economic toll ranging from $796m to $6.3bn. (Also see "CDI Market Snapshot: Microbiome Therapies Begin Descent On Landscape" - In Vivo, 19 Dec, 2022.) Antibiotics remain the only treatment for initial CDI and fecal microbiota transplantation (FMT) has proven highly effective for recurrent cases of CDI, but it carries risks of pathogen transmission, is only available under FDA enforcement discretion, and requires that a donor be screened, or that a clinician purchase stool from a stool bank.
“The key to both of these products being approved is that providers who wouldn't have gone through the rigmarole of doing FMT previously, wouldn't have screened donors, wouldn't have bought stool from a stool bank now have something that they can prescribe that is safe and effective,” Paul Feuerstadt, assistant clinical professor of medicine, Yale University School of Medicine, told In Vivo. “That, to me, opens up opportunities for patients and providers in a huge way.”
The estimated $1bn CDI market has drawn interest and investment from a number of companies targeting the microbial dysbiosis at the heart of the illness. Rebyota and Vowst are the only approved microbiome-based treatments for rCDI, but several others are in the pipeline. Finch Therapeutics Group, Inc.’s single pill microbiome treatment, CP101, was next in line for approval until the company recently and abruptly discontinued that program as it shuttered its business. (Also see "Finch To Wind Down, Seek Value For Pipeline Assets And IP" - Scrip, 24 Jan, 2023.) That gives Seres and Ferring several years before the arrival of the next potential entrant, Vedanta Biosciences, Inc.'s VE303.
Both treatments have strong efficacy and safety, but there are some differences in their supporting bodies of evidence. For example, according to subpopulation analyses presented at Digestive Disease Week 2023, Rebyota is safe and effective in inflammatory bowel disease (IBD) and immunocompromised patients, two populations at increased risk of rCDI and of more severe outcomes. Those findings are “a big deal,” said Feuerstadt, noting that he is not aware of similar data for Vowst.
Conversely, the Phase III Vowst study included difficult-to-treat patients with at least two recurrences of CDI, while the Rebyota pivotal Phase III trial enrolled those with one or more recurrences, an arguably less refractory population.
Despite the differences in supporting evidence and mode of administration, “I think the best product is the one that patients gain access to,” said Feuerstadt, who has been involved in research on both Vowst and Rebyota.
Like Allegretti, he said patients will guide the choice of treatment, after a thorough explanation of the risks and benefits and the supporting data, and a consideration of the modes of administration.
“I don't practice in a paternalistic way. We decide together what they're most comfortable with,” Feuerstadt emphasized.
While Allegretti indicated oral administration would not always be the first choice for patients, a June 5 note by analysts at TD Cowen placed a strong emphasis on the value of Vowst's pill form, saying there was a clear patient preference for this approach. They also noted concerns about a lack of dose response seen in the Rebyota clinical program.
With patients ultimately expected to decide between Rebyota and Vowst, Seres and Ferring executives are thinking how they can influence end-users' decisions. In Vivo contacted both companies to hear more about their respective strategies.
Eric Shaff
President And CEO
Seres
Vowst was approved on April 26 and became available to patients on June 5. Seres entered into an agreement with Nestlé Health Science in July 2021 to jointly commercialize Vowst in the US and Canada. Under the terms of the agreement, Nestlé Health Science will leverage its existing infrastructure, including a gastrointestinal sales force and payer access team, to commercialize Vowst and will profit share 50/50. The Nestlé sales teams have been educating healthcare practitioners and seeking insurance coverage for Vowst over the past two months to ensure broad patient access to this important new therapy.
In connection with the 2021 License Agreement with Nestlé, Seres received an upfront payment of $175m and an additional $125m following the FDA approval. There are also additional potential milestones that Seres could earn based on Vowst sales.
Seres is driven by our mission of improving patients’ lives through revolutionary microbiome treatments. We recognize that these treatments only matter if they are accessible, which is why we price our therapies based on the value they deliver and with the goal of broad access.
Vowst is the first and only FDA-approved microbiota-based therapeutic with an oral modality, which is important for patients suffering from recurrent CDI (rCDI), an incredibly difficult-to-treat infection.
We, along with our collaborators at Nestlé, have priced Vowst at the wholesale acquisition cost of $17,500 per course of therapy. This price reflects the substantial value that Vowst offers to patients and society, and of course, is the price before any mandated or discretionary discounts and rebates to payers.
We considered the following factors on the value Vowst provides to people with rCDI, their families, insurers, hospital systems and physicians: established efficacy in preventing recurrence; potential cost offsets to the healthcare system; Vowst’s innovation as a first-of-its-kind orally administered microbiota-based therapeutic designed to address the root cause of CDI recurrence; and oral dosing and the ability of patients to administer Vowst without the need for additional medical procedures.
Both Seres Therapeutics and Nestlé Health Science are committed to broad patient access with minimal out-of-pocket costs, and our patient support program—the Vowst Voyage program—offers financial assistance to qualified patients and provides help to start treatment without hassle or delay.
We believe that Vowst could transform how rCDI is managed. In our market research and discussions with the CDI community, preventing recurrence is the number one unmet need cited by physicians and patients, and we are pleased to be able to address this critical issue.
We are also well-aware that all launches take time and substantial effort. Some items we are working to address include education of the medical community about this new treatment approach, streamlining Vowst administration following antibiotic treatment, and obtaining broad patient access for Vowst from payers.
The data from the Vowst Phase III studies provided a very clear demonstration of a favorable efficacy and safety profile. Based on our discussions with the medical community, there is already a strong appreciation for the value Vowst can bring to them and the patients they treat. However, as with all new medicines, physicians obtaining personal experience with their own patients over time will be important.
The Vowst Phase III development program evaluated numerous rCDI patient subgroups (e.g. first recurrence vs. multiple recurrent), and we were pleased to obtain compelling data across a broad swath of patient groups. We continue to evaluate whether to initiate any new studies with Vowst in rCDI subgroups.
Our company focus is on the successful commercialization of Vowst and enabling broad access across eligible patients. We also look forward to continuing to present scientific and clinical data at upcoming medical meetings.
With a strong clinical profile and an oral modality, we believe Vowst will continue to be an effective option for patients suffering from this debilitating disease. Also, given the compelling Vowst profile, this will be a challenging bar for other prospective therapies to meet.
Supported by Vowst clinical data, Seres continues to advance its research with a focus on the development programs targeting infection protection in medically compromised patients.
SER-155, an investigational microbiome therapeutic, is being evaluated in a Phase Ib study in patients receiving allogeneic hematopoietic stem cell transplantation to reduce incidences of gastrointestinal infections, bloodstream infections and graft-versus-host disease, and we are also conducting research to inform further development of microbiome therapeutics for ulcerative colitis.
Lionel Fajolle
Vice President Of Specialty Care
Ferring Pharmaceuticals US
Our main mission has always been and continues to be centered on the patient. In the many months leading up to the approval and launch of Rebyota, we were relentless in our preparation and focus on the patient. At Ferring, we strongly believe that ensuring broad patient access as well as an optimal patient experience with only one dose are keys to addressing the significant burden placed on patients and the healthcare system from rCDI.
A first mover advantage is first and foremost a demonstration of leadership in action. Being first to market concretely translated into being first to help patients, and that sense of pride is what drives us forward. We never took our first mover advantage for granted as it is the fruit of the outstanding work of our R&D and regulatory teams, and that effort led to a positive outcome at the FDA advisory committee meeting and ultimately in product approval.
To further demonstrate Ferring’s leadership in action and well before our FDA approval, we identified and made a deliberate decision to address a significant microbiome knowledge gap that existed with both patients and practitioners. I am proud to say that our disease state educational content has been equally praised by many healthcare providers and C. difficile patient associations.
We believe Rebyota offers a compelling value proposition to all stakeholders, including physicians, patients, and healthcare systems, with one dose delivered by a healthcare provider in minutes during one visit. Since product launch in January, we have received very positive feedback from both healthcare providers and payers. Over the past few months, we have already achieved many formulary acceptances from national and regional payers, reinforcing the value proposition we offer to both patients and healthcare systems.
In addition, a growing number of early trialists are already reordering Rebyota, further demonstrating that the product delivers on the expected value proposition.
We are establishing a new standard of care, changing the practice of medicine for rCDI patients, and that requires a significant cross functional effort. The commercial team is just one piece of that puzzle. Any time you embark on a journey to disrupt medical practice, it takes a significant coordinated effort amongst multiple functions, multiple stakeholders across multiple settings to challenge the status quo.
Despite the potential challenges that surface along the way, we are determined to accomplish our goal – breaking the vicious cycle of rCDI and delivering on our core mission at Ferring, to help people live better lives. This is what being a leader in action must do to establish a new standard of care for the prevention of recurrent C. diff infection.
Real-world data will further reinforce the true power of the microbiome and the role that live biotherapeutic products like Rebyota play not only in the prevention of rCDI but also other potential diseases to be further explored.
With Rebyota, in an effort to advance patient care, we continue to look at patient populations seen in clinical practice. At DDW, we presented two analyses of data, one for patients with underlying inflammatory bowel disease and one for immunocompromised patients. Both of these patient groups are at an elevated risk for rCDI but are often excluded from prospective clinical trials.
Launching a new product is always an exhilarating journey filled with challenges and rewards. We have a series of milestones and achievements that we are well on our way to accomplishing in terms of payer acceptance, hospital usage and medical community adoption. Our differentiated value proposition with all of these stakeholders confers a unique position on Rebyota in the prevention of rCDI. We remain focused on changing the standard of care for rCDI patients and ensuring those who need Rebyota have access to it.
Finally, the main catalyst from day one has been the patient. Their stories and all of the testimonials we have collected fuel our unwavering commitment to our mission every day.
There are approximately 125,000 patients in the US suffering from recurrent C. diff infection every year for whom the therapeutic approach to care has remained fairly unchanged for a long time. Being able to contribute toward challenging that status quo and establishing a new standard of care is truly inspiring. We believe that offering multiple therapeutic options for these patients will ensure a more individualized treatment approach and in turn, help people live better lives.
Ferring has embarked on a bold course, pioneering a new category of microbiome-based therapeutics to help people live better lives. We are a company of firsts and in our 70+ year history, we have employed our scientific leadership to innovate and develop groundbreaking medicines. Harnessing the power of the microbiome and developing new microbiome-based medicines is part of our legacy and future.