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[posting]48373736[/posting] ZS Pharma - LifeSci Advisors Update, ZS-9 is 'Poised to Change the Treatment of Hyperkalemia'; Summary of KOL Event - Nov 21, 2014 - Jerry Isaacson, Ph.D.(AC) - - On November 19th, ZS Pharma (NasdaqGM: ZSPH) hosted a Research and Development day that featured three Key Opinion Leaders (KOLs) from the specialties expected to prescribe ZS-9, an Emergency Medicine physician, a Cardiologist, and a Nephrologist. ZS-9 is being developed to treat hyperkalemia, or excess potassium, with NDA and MAA filings expected in the first half of 2015. Based on their compelling presentations, we came away from the event especially impressed with ZS-9’s rapid onset of action, tolerability profile, and potential for ZS-9 to manage both acute and chronic cases of hyperkalemia, without the safety issues related to current treatments. There are approximately 4 million patients in the US with hyperkalemia, and we estimate that the market opportunity significantly exceeds $1 billion annually in the US alone. Strong Clinical Data Package Supports Acute and Chronic Hyperkalemia Treatment. ZS Pharma has completed 4 clinical trials with potassium (K+) binder ZS-9, meeting the primary endpoints in all studies. The data consistently demonstrate ZS-9’s ability to safely and rapidly lower serum K+ levels and maintain normokalemia (potassium of 3.5-5 mEq/L). In the most recent trial, the median time to serum K+ normalization was 2.17 hours with greater than 90% of patients receiving 10 or 15 grams of ZS-9 maintained normokalemia for 3 weeks. A 1-year safety study (ZS005) is ongoing. Company management noted that based on extensive discussions with US and European regulators, if ZS Pharma continues to meet trial endpoints, the data would support a label that includes acute and chronic hyperkalemia. ZS-9 "will" be Revolutionary for the Acute Treatment of Hyperkalemia. Dr. Frank Peacock, an emergency room physician at the largest ER in Houston, TX, discussed the treatment path for an average patient with acute hyperkalemia. His emergency department has extensive experience treating hyperkalemia and sees 30 hyperkalemic patients on a typical day. Most methods for managing serum potassium are temporary and patients ultimately require emergency dialysis. However, the availability of a safe and effective solution to reduce serum potassium rapidly could not only replace existing therapies, but also potentially eliminate the need for emergency dialysis. As the agent with the fastest onset of action, ZS-9 would be very likely be the exclusive agent on his hospital formulary. Importantly, 50% of hyperkalemia patients are first diagnosed in the ER. This represents an entry point for ZS-9 where patients receive initial treatment to normalize K+ levels and then remain on long-term therapy to prevent future acute events. Expected Upcoming Milestones H1 2015 –Expected NDA & MAA submission for ZS-9 for the treatment of hyperkalemia. H1 2016 –Potential approval and commercial launch of ZS-9. Huge, Readily Accessible Market Opportunity. Based on 2011 IMS data for the US, 200 million grams of Kayexalate, the current standard of care, are sold annually in the non-retail setting. Using an average 15 gram dose, this represents over 13 million doses of Kayexalate administered in the hospital setting. Given ZS-9’s clinical profile, we expect it to be used as an alternative to Kayexalate, and even using conservative pricing and the capture of only Kayexalate used in hospitals, we believe sales for acute hyperkalemia could reach $300 million annually. Should these acute patients remain on ZS-9 for only a fraction of a year, the product could reach >$1 billion annually. ZS-9 Data Published in JAMA Shows Significant Benefit for Heart Failure and Chronic Kidney Disease Patients. Cardiologist Dr. Mikhail Kosiborod presented full results from ZS Pharma’s Phase III (ZS004) study at the R&D/KOL event and at the American Heart Association Scientific Meeting last weekend.1 The results were also published in the Journal of the American Medical Association.2 Dr. Kosiborod highlighted the diversity of patients included in the study. The trial enrolled 258 patients with hyperkalemia who were treated with 10 grams of ZS-9 three times per day during a 48 hour acute phase. Patients who achieved normokalemia were randomized to once daily ZS-9 (5, 10, or 15 grams) or placebo for 28 days as part of a randomized withdrawal period. There was no upper limit for baseline serum K+, no lower limit for estimated glomerular filtration rate (eGFR), and the study enrolled patients with many different co-morbidities such as heart failure (HF), chronic kidney disease (CKD), and existing RAAS inhibitor use. - This trial gives an accurate view of the patients that will be treated in the clinic. ZS-9 displayed similar activity in all subpopulations, confirming its real-world potential as a hyperkalemia treatment. In support of this notion, Dr. Bruce Spinowitz, a Nephrologist, discussed how medications such as RAAS inhibitors can disrupt the body’s K+ balance and trigger hyperkalemia. - We estimate that 1.4 million CKD and HF patients would benefit from a K+ control agent to enable therapeutic doses of cardio-protective RAAS inhibitor therapy. This represents a staggering multi-billion dollar opportunity. Excellent Safety Profile Supports Approval. Dr. Kosiborod also presented safety data from trial ZS004, reporting a tolerability profile similar to placebo and no treatment-related serious adverse events. Out of 258 patients, there were 14 cases of edema, 13 were peripheral (foot and ankle) edema, and 7 cases did not require treatment modification. Dr. Kosiborod gave an excellent review of the overall edema cases in all patients treated with ZS-9. Based on his analysis, he believes the single case of generalized edema was likely related to underlying co-morbidities and the fact that the patient recently discontinued their diuretic, and was therefore a false signal. Consistent with the strong safety and tolerability observed in ZS004, ZS Pharma CEO Robert Alexander announced new toxicology data clearly showing that ZS-9 is not systemically absorbed. Dogs treated for 9 months had no detectable ZS-9 in their urine, corresponding to levels at or below parts per billion. This confirms the human data collected in ZS004. Overall the data show that ZS-9 has an excellent safety and tolerability profile. ZS-9 "will" become the Standard of Care, Despite a Head Start for Patiromer. Relypsa (NasdaqGS: RLYP) is developing a competing product for hyperkalemia, patiromer, which is an organic polymer that exchanges calcium ions (Ca2+) for K+. Relypsa recently filed an NDA for patiromer. There are several features of ZS-9 that set it apart from patiromer and will make it the standard of care: - Rapid onset of action: Statistically significant reduction in serum potassium by 1 hour for ZS-9 compared to 7 hours for patiromer. - Convenient dosing: ZS-9 is a once daily treatment for maintenance of hyperkalemia compared to twice daily for patiromer. - Strong tolerability profile: The rate of GI side effects from ZS-9 is similar to placebo compared to higher rates of diarrhea, constipation, and nausea for patiromer. - High ion selectivity: ZS-9 is highly selective for potassium whereas patiromer can non-specifically bind other ions including magnesium. Ion Selectivity/Release Deserves Scrutiny. The ion selectivity/release of each compound in particular may have profound implications for extended use. Hypomagnesemia occurred in 24% of patients taking 15 grams of patiromer twice daily in a trial with heart failure patients,3 and there were 8 cases (3%) in the induction phase of Relypsa’s Phase III study. Patiromer’s mechanism of action is to exchange Ca2+ for K+. Calcium is found in vascular deposits that are more likely to occur in CKD patients due to imbalances in bone metabolism. The deposits can contribute to the development of heart disease. For these reasons, CKD patients are often prescribed non-calcium based phosphate binders to manage hyperphosphatemia and minimize new calcium deposition in the arteries.4 Although Relypsa has not reported elevations in serum Ca2+from its clinical studies, patiromer approximately contains 3,200 mg of Ca2+ in a daily dose. The Cleveland Clinic recommends Ca2+ intake of 1,400-1,600 mg/day, not to exceed 2,000 mg/day, for patients with CKD. Most Ca2+ comes from dietary intake, and the long-term exposure to additional Ca2+ via patiromer may represent an issue for CKD patients, which make up the majority of hyperkalemia cases. ...- jisaacson@lifescicapital.com (646) 597-6991 https://lifesci.bluematrix.com/sellside/EmailDocViewer?encry… |
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| Autor (Datum des Eintrages): | Popeye82 (21.11.14 18:58:52) |
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