Innovation

Ardelyx’s business innovation is a medication marketed under the name IBSRELA

(Tenapanor). IBSRELA is available in the U.S. and Canada to treat adults with Irritable Bowel Syndrome with Constipation (IBS-C). IBSRELA is a sodium/hydrogen exchanger 3 (NHE3) inhibitor. It works by inhibiting NHE3 in the intestine. IBSRELA was approved by the FDA in September 2019 and launched by Ardelyx in April 2022.

IBSRELA is the first-in-class medication, meaning that it is the first and only NHE3 inhibitor that is FDA approved for the treatment of IBS-C. No generic version of IBSRELA is currently available in America. IBSRELA emerged from Ardelyx’s discovery model and is the result of their scientists’ extensive study and understanding of the sodium transport in the intestine. Through the use of the discovery model, which recreates environments within certain areas of the gastrointestinal tract, scientists at Ardelyx have been able to explain new and previously unexploited ion transport mechanisms.

The discovery of the compound started 14 years ago. There have been a multitude of people involved in the development of IBSRELA, ranging from the original founders of the company, Dominique Charmot, Ph.D., Jean Frechet, Ph.D. and Pete Schultz, Ph.D., to the dedicated research team and the more than 1200 patients who volunteered to participate in the two successful Phase 3 clinical trials. The two trials lasted 12 weeks and 26 weeks, respectively, with a controlled placebo. Both trials met their primary endpoints.

Ardelyx’s mission is “to discover, develop and commercialize innovative, first-in-class medicines that meet significant unmet medical needs.” IBSRELA is the first product to fulfill the company’s mission. It was identified and developed by Ardelyx’s scientists, and now the company is delivering this first-in-class drug to patients whose treatment needs were not previously being met. IBSRELA is “an incredible testimony to our mission.”

Inspiration

“Patients are the center of what we do, and they are the motivation to do what we do.” The patients inspire Ardelyx to develop first-in-class treatments in areas of high unmet need where there can be a significant impact. The first-in-class aspect is huge for Ardelyx. They are not looking to manufacture drugs that are simply a variation of an existing medication. They are looking for innovations and discoveries that are meaningfully different, and that is why their focus on the “unmet need” is so important.

The idea for IBSRELA came about through Ardelyx’s understanding of sodium transport by the antiporter known as NHE3. The compound was designed to selectively inhibit NHE3 in the intestine and to remain non-absorbed in order to avoid exposure in the kidney. Upon discovering the capabilities of the molecule, Ardelyx was inspired to fulfill the sizable, unmet need of patients by developing and commercializing a product that would help treat IBS-C, using a novel mechanism of action compared to other medications on the market.

Ardelyx looked at treatments that would be minimally absorbed within the gut. They wanted “a novel mechanism for unmet needs.” The company explained, “Patients are the number one motivator, where there’s a high unmet need.” They stated, “Hearing the stories of people who have benefitted from this treatment is the most rewarding part, being able to go to work and feel like you are helping people.” Although Ardelyx considers itself a small company with just over 100 employees, they describe it as “fearless, dedicated, and passionate.”

Overall impact

Ardelyx is working with the specific molecule used in IBSRELA to apply it to other indications. This molecule is quite versatile, and Ardelyx is working to develop Tenapanor for other indications, including for the control of serum phosphorus in adult patients with Chronic Kidney Disease on Dialysis under the brand name XPHOZAH®. XPHOZAH is currently awaiting guidance from the Food and Drug Administration’s Office of New Drugs in response to its second-level appeal to XPHOZAH’s New Drug Application. The company recently announced that an FDA Advisory Committee voted that the benefits of XPHOZAH outweigh its risks.

In addition, Ardelyx is currently researching and working with other molecules to develop first-in-class treatments for hyperkalemia and metabolic acidosis, two chronic kidney disease-related health issues. Ardelyx has development underway and several pipeline programs. Ardelyx generates product sales from IBSRELA, which totaled $6.9 million from launch in April through the end of the company’s with each additional product that is approved, which can be reinvested to fuel further growth and to advance their research and development efforts to support the growing pipeline and their mission.

While Ardelyx is committed as an organization to managing its environmental impact, due to the company’s small size, its impact third fiscal quarter ended September 30, 2022, as well as collaboration revenue from its partners in Canada and Japan. Ardelyx will be able to help more people and see increased product sales.

on the environment is not significant. The biggest impact of IBSRELA is the social impact that this innovation has on the patients it helps. Current medications aren’t fully effective for many patients who live with IBS-C. This strongly impacts patients’ daily lives. It’s harder for people suffering from IBS-C to enjoy social activities due to their symptoms. Ardelyx finds the testimonials from individuals who have been helped by IBSRELA to be the most rewarding aspect of their efforts. As demonstrated in Ardelyx’s clinical trials, early results from the launch appear to indicate that patients are benefiting from IBSRELA.

Diarrhea is the most common side effect of IBSRELA; however, it is generally mild to moderate and usually doesn’t last more than one week with continued treatment. For those who do experience severe diarrhea, it is advised to stop taking the medication and to call the doctor. The other most common side effects include swelling, or a feeling of fullness or pressure in the abdomen (distension), gas, and dizziness.

Since their medicine came to market in April, patients have had a new treatment option where other medications were not fully effective. IBSRELA provides new hope for patients with IBS-C to be able to live more normal lives. Paul explained how it's terrific “to hear that someone used our medicine after not having success with others. One lady, whose husband was in the same situation and came with her to her doctor’s appointment, asked to try this treatment. This is a testament that [IBSRELA is] working well for some patients.”

Ardelyx has conducted and published data from two successful Phase 3 clinical trials supporting IBSRELA, both of which met their primary endpoint. In the company’s first clinical trial, T3MP0-2, improvements from baseline in average weekly bowel movements, abdominal pain, bloating, and other abdominal symptoms were observed as early as Week 1, with improvement sustained through the end of the 26-week trial. Additionally in the Phase 3 trial T3MP0-2, patients treated with IBSRELA reported a 41% improvement in quality-of-life score from baseline to end of treatment, and the vast majority of patients reported satisfaction with treatment. The most common side effect in clinical trials was diarrhea, occurring in 16% of patients (4% placebo), and was most commonly mild-to-moderate and transient, resolving in ≤1 week with continued treatment.

Business benefit

With this innovative medicine only coming to market 7 months ago, we can look at the most recent earnings and financial reports to determine the impact. Product sales for IBSRELA were $6.9 million during the first three quarters of 2022, beating many investor expectations. For the first three months of 2022, Ardelyx reported a net loss of $0.53 per share, compared to a net loss of $1.21 during the first three months of the fiscal year 2021.

Social and environmental benefit

IBSRELA benefits society by positively impacting patients’ lives who haven’t had success with previously existing medications but are now experiencing success with IBSRELA. From a patient perspective, IBS-C is a debilitating disorder that causes people to miss work and family events. Many social activities revolve around food in our society, and being able to participate with others in these kinds of activities can have a profound impact on one’s overall health and well-being, physically and mentally. It is life-changing and life-altering for the patients whose lives have been impacted in a very positive way with IBSRELA.

“In a survey of more than 1300 people with IBS‑C, half reported their symptoms as very/extremely bothersome, and as having a negative impact on their productivity and personal activities. Despite treatment, more than three-quarters of those people continued to experience belly pain and/or constipation”

In an effort to help ensure all patients have access to IBSRELA, Ardelyx offers ArdelyxAssist, a Copay Assistance program for patients who meet certain criteria.

Interviews

Sindy Wan, Director of Facilities and Operations

Michelle Limaj, Vice President of Legal

Paul Pereira, Vice President, Head of Global Patient Advocacy

Caitlin Lowie, Vice President of Corporate Communications and Investor Relations.