AzurRx BioPharma Inc. (NASDAQ: AZRX)
Since first covering AzurRx in December of 2016, many investors have asked me to further expand on the technology and methods that the company is developing to treat both chronic pancreatitis and cystic fibrosis. Because the company's pipeline is actually far deeper than just developing treatments for those two indications, I reached out to AZRX management to allow them to provide a specific overview of the progress and technological differences being developed at the company.
In the first of a three part, C-Suite exclusive, AZRX's management and medical team responded, in specific detail, to investor interest and questions.
Q. First off, thank you for taking the time to both respond to and explain the AZRX pipeline and technology.
As a primary clinical focus, AzurRx has said that the company is aiming to reduce the daily pill burden for patients that have either chronic pancreatitis or cystic fibrosis. What exactly do you mean?
Thank you for reaching out. Yes, AzurRx, with its MS1819 compound, aims to improve adherence to therapy and potentially treatment outcomes in patients with chronic pancreatitis and cystic fibrosis. The plan is to materially decrease the pancreatic enzyme replacement pill burden to 5 to 8 capsules per day with MS1819, down from over 25 capsules daily with existing porcine agents.
Q. What is the significance of pill burden reduction? Will the decrease have a material benefit other than just convenience and patient dosing compliance?
Pill burden has historically been an issue for patients and clinicians. Experience and data show that large pill requirements generally lead to poor compliance and are associated with poor treatment outcomes. Notable examples of where pill burden has been reduced, resulting in improved outcomes include HIV, hypertension, chronic kidney disease and diabetes.
In the early days of the HIV epidemic, patients took upwards of 40-50 pills a day with generally poor outcomes, compliance and polypharmacy related adverse events. Due to drug development advances, including novel co-formulations, the current standard of care broadly consists of treatment with a single pill once daily.
While the convenience benefit of once daily administration appears obvious, it is also clinically important. In one study, published in the Journal of Pharmacotherapy, patients with single tablet regimens (STR) had better outcomes than patients with multiple tablet regimens (MTR).
Q. So, single tablet measurements, or even a significantly reduced bill burden, may actually have more therapeutic affect?
In studies, STR patients were more adherent, had a lower risk of hospitalization and higher proportion of patients with viral suppression. Similarly, in another HIV study published in the journal Clinical Infectious Disease, the authors concluded “higher pill burden was associated with both lower adherence and worse virologic suppression.”Subsequently, in a meta-analysis of 19 studies of 6,312 people, higher pill burden was associated with lower rates of adherence (p=0.0004).There was also a significant association between higher pill burden and reduced chances of achieving virologic suppression (p<0.0001).Notable HIV products that offer reduced pill burden include Gilead’s set of once daily products; Atripla, Complera, Genvoya, Odefsey and Stribild. Also,ViiV’s (a partnership between GlaxoSmithKline and Pfizer) Triumeq is a once daily product.
Q. Some studies show that higher pill burdens may contribute to even worse clinical outcomes. Are the reports accurate?
In the treatment of hypertension, higher pill burden has also been linked with worse outcomes. Notably, a study of 17,000 adults, published at ASH 2014, showed that adherence among patients treated with single-pill therapy was 55.3%, compared with rates of 40.4% for patents with double-pill therapy and 32.6% for those on triple-pill therapy. The clear conclusion from these data is lower pill burden in the antihypertensive setting leads to improved adherence.
Q. There was a study of pill burden, in relation to kidney disease. Is AZRX tracking that study?
Absolutely. In chronic kidney disease, lower pill burden has been shown to be beneficial. In a study of 5,262 hemodialysis patients participating in the Dialysis Outcomes and Practice Patterns Study (DOPPS), it was demonstrated that patients prescribed a higher number of phosphate binder pills were more likely to have worse serum phosphorus levels. This supported the concept that non-adherence to large pill burdens can result in poor patient outcomes. Additionally, this study showed a clear pattern of rising non-adherence with increased pill burden in hemodialysis patients. Marketed phosphate binders that allow reduced pill burden include Fresenius’ Velphoro and Sanofi’s Renvela.
Q. Have there been any supporting studies to support the beneifts from a lower bill burden?
Yes, there is supporting research. From the Journal of General Internal Medicine, a study evaluated 9,170 people with diabetes treated with a fixed-dose combination product or two medications. Adherence to the treatment regimen was 12.8% higher the single-component arm versus the two medication arm. Combination Type II diabetes products include Merck’s Janumet, GlaxoSmithKline’s Avandamet, Takeda’s ACTOplus met and AztraZeneca’s Xigduo XR, which all provide reduced pill burden.
Q. Several investors were interested in getting more information about the lipase market and the potential for MS1819 to have a material impact in treating targeted indications. Can you elaborate on the market and benefits?
With the US pancreatic enzyme replacement market currently generating about $900 million in sales, MS1819 stands to have a sizable commercial presence. The reduction in pill burden associated with MS1819 is likely to confer a material adherence advantage to patients. This in turn should result in robust market uptake.
Q. Since we mentioned MS1819, AZRX's lead candidate, can you provide some insight into that compound?
MS1819-SD is our lead therapeutic candidate. It's a yeast based recombinant lipase intended to treat diseases in the pancreas, specifically exocrine pancreatic insufficiency (EPI) that is related to chronic pancreatitis (CP) and cystic fibrosis. We currently have an on-going phase II trial of MS1819-SD and are currently recruiting and treating patients in Australia and New Zealand, and we expect to publish initial efficacy results in the first half of 2017.
The phase I trial, like most, was geared to demonstrate positive safety and tolerability data, which we did. In addition to just showing safety, though, MS1819-SD also demonstrated the potential to provide a materially improved efficacy profile and dramatically reduced pill burden. In current treatment applications, it is not uncommon for patients to be prescribed up to 25- 40 pills per day to treat EPI, an issue that AZRX is intently focused upon changing. Current data suggests that an approved AZRX therapy may potentially offer patients the ability to ingest just 1-2 capsules per meal, and at the same time may benefit from an equal, or potentially greater therapeutic affect.
Q. Suggesting that the overall data from the on-going trial's for MS1819-SD remains positive, how significant is the market potential for AZRX?
First, we expect that the trials will continue to demonstrate positive patient results. Assuming approval, AZRX will advance the product into a market that has the potential to treat over 100,000 patients in the U.S., and an additional 30,000 patients with EPI caused by cystic fibrosis. As we noted in prior releases, we are targeting the replacement of standard care, which is treatment with porcine replacement pills. In 2015, data estimated the market at $820 million in the U.S. alone, and roughly $1.5 billion dollars globally, this is according to market data provided by the National Pancreas Foundation.
Q. Finally, investors asked for detail about AZRX's pipeline, specifically near term initiatives. Can you provide some color on that front?
Beyond MS1819-SD, AZRX's next leading developmental stage agent is AZX1101, which also has broad market potential. AZX1101 is a complex biologic being developed to target and prevent hospital acquired bacterial infections. It's mechanism works by inhibiting the activity of a broad range of antibiotics from acting within the GI tract. Data is showing that AZX1101 may prevent toxicity of intravenous antibiotics to gut bacteria, which may deliver a commercial market that holds enormous potential. Data published by the CDC estimates that over 1.7 million hospital associated infections are reported each year, and the results of these infections contribute to the death of almost 100,000 patients a year, and has an estimated annual cost burden to the health care system of roughly $11 billion per year.
It's our goal to file an Investigational New Drug (IND) application for AZX1101 prior to the end of 2017, with a primary indication toward treating or preventing clostridium difficile infection. Beyond that indication, though, we expect that AZX1101 may also demonstrate broad and potentially lucrative applications for AZX1101 to treat a substantially higher number of bacterial infections.
As previously noted, AZRX is well positioned to advance clinical initiatives on multiple fronts, taking advantage of potential drug approvals outside of the United States, which may offer a more streamlined process toward drug approval. With AZRX having a clinical presence, with on-going trials in countries such as Australia and New Zealand, the potential for expedited approval is in place, a decision that can allow AZRX to become a revenue generating company much sooner than expected.
Special thanks to the AZRX medical and management team for providing responses to investor questions, and ask investors to stay posted to CNA Finance for the second installment of this three part series.
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