|Conatus Announces Top-line Results From Multicenter Phase 2 Portal Hypertension Trial; Pulmatrix to Report Clinical Data on PUR0200|
|By Josh Gee|
|Wednesday, 23 September 2015 18:37|
Below is a look at some of the headlines for companies that made news in the healthcare sector on September 23, 2015.
Conatus Pharmaceuticals Inc. (NASDAQ:CNAT) announced the company's exploratory Phase 2 Portal Hypertension (PH) clinical trial of emricasan, a first-in-class, orally active pan-caspase inhibitor, met the following primary endpoints: a) a clinically meaningful and statistically significant change from baseline in hepatic venous pressure gradient (HVPG), a measurement of pressure in the portal vein, in patients with liver cirrhosis and severe portal hypertension (HVPG ≥12 mmHg); and b) a statistically significant change from baseline in cleaved Cytokeratin 18 (cCK18), a mechanism-specific biomarker of excessive cell death that contributes to chronic inflammation, in the total evaluable liver cirrhosis patient population.
The open-label PH trial was conducted at nine U.S. sites and enrolled 23 patients (22 evaluable) with portal hypertension and compensated liver cirrhosis that was predominantly due to nonalcoholic steatohepatitis (NASH) or hepatitis C virus (HCV), including patients with active HCV infection and patients who had a sustained viral response (SVR) to antiviral therapy. Portal hypertension, or elevated blood pressure in the major vein feeding into the liver, was confirmed by HVPG measurement >5 mmHg at baseline and measured again after treatment with 25 mg of emricasan orally twice daily for 28 days. Patients were divided according to the HVPG therapeutic threshold of 12 mmHg, which indicates more severe portal hypertension. Reducing the HVPG to below 12 mmHg or reducing HVPG by ≥10% or ≥20% has been strongly associated with clinical benefit in this patient population.
The HVPG endpoint was analyzed in: a) patients with baseline HVPG values ≥12 mmHg (N=12); b) patients with baseline HVPG values <12 mmHg (N=10); and c) all evaluable patients (N=22). HVPG measurement was standardized, and tracings were evaluated by a single expert reader not otherwise involved in the PH trial. HVPG decreased by a mean of 3.7 mmHg from the mean baseline of 20.6 mmHg in the higher baseline HVPG group (p<0.003), with 8 of 12 achieving a ≥10% decrease, 4 of 12 achieving a ≥20% decrease, and 2 of 12 achieving reductions below 12 mmHg. The changes from baseline HVPG were not statistically significant in the lower baseline HVPG group (+1.9 mmHg mean increase from mean baseline of 8.1 mmHg; p=0.12) or the total evaluable patient population (–1.1 mmHg from mean baseline of 15.2 mmHg; p=0.26). The cCK18 endpoint, analyzed in the total evaluable patient population, showed a statistically significant reduction (p<0.03) from baseline. Consistent with results from prior trials, emricasan was safe and well tolerated in the PH trial, with no dose-limiting toxicities and no drug-related serious adverse events. Detailed results are expected to be presented in a future scientific forum.
As liver cirrhosis progresses, portal pressure increases and hepatic function is eventually lost. Importantly, portal hypertension is largely responsible for events of hepatic decompensation including variceal bleeding, ascites, and encephalopathy, which contribute substantially to morbidity and mortality in these patients. By lowering elevated portal pressures, emricasan has the potential to decrease the risk of hepatic decompensation in liver cirrhosis patients over the short term, and may improve both liver function and structure over the long term through anti-inflammatory and anti-fibrotic effects.
David T. Hagerty, M.D., Executive Vice President of Clinical Development at Conatus, said, "We were excited to demonstrate that a drug candidate with the potential to achieve long-term resolution of fibrosis and cirrhosis also has the ability to induce a rapid and clinically meaningful reduction of severe portal hypertension. The reduction of portal pressure over a relatively short time frame in the patients with therapeutically relevant portal hypertension may reflect the initial impact of emricasan on the hyperdynamic circulation that is the predominant contributor to portal hypertension as cirrhosis progresses and/or a direct effect upon intrahepatic vasculature resistance. Future studies will be needed to assess the relative contribution of these mechanisms to the observed clinical effect. Decreasing HVPG has been identified by the FDA (U.S. Food and Drug Administration) as a validated, objective measure that may be acceptable as a surrogate endpoint for clinical trials of patients with liver cirrhosis. These results set the stage for future Phase 2b clinical trials in patients with cirrhosis and therapeutically relevant portal hypertension."
"These results demonstrate that emricasan can cause a clinically meaningful improvement in portal hypertension in the liver cirrhosis patients who need it most," said Conatus co-founder, President and Chief Executive Officer Steven J. Mento, Ph.D. "Specifically, patients with therapeutically relevant baseline portal hypertension showed meaningful decreases in HVPG. We believe the results from this trial establish the near-term effects of emricasan on portal hypertension. We are evaluating emricasan's potential longer-term effects on liver function and liver structure in our other two ongoing clinical trials: the Phase 2 Liver Cirrhosis (LC) trial and the Phase 2b post-transplant trial."
"Even though the number of patients in this trial was small," added Dr. Hagerty, "Conatus was encouraged by the consistency of responses in patients with portal hypertension and cirrhosis due primarily to NASH or HCV. These results further support our view that apoptosis and inflammation are important common mechanisms for progressive liver disease across multiple etiologies, and that treatment with emricasan is likely to provide both short- and long-term clinical benefits."
Conference Call/Webcast/Presentation --- Conatus will host a conference call and webcast at 8:30 a.m. Eastern Time on Thursday, September 24, to discuss the top-line results and provide a mechanism-focused overview of liver cirrhosis and portal hypertension. To access the conference call, please dial 877-312-5857 (domestic) or 970-315-0455 (international) at least five minutes prior to the start time and refer to conference ID 45793794. An associated presentation and live and archived audio webcast of the call will be available in the Investor Center of the company's website at http://ir.conatuspharma.com/events.cfm.
About Emricasan Clinical Development --- To date, emricasan has been studied in over 600 subjects in fifteen clinical trials across a broad range of liver disease etiologies and stages of progression. In multiple clinical trials, emricasan has demonstrated statistically significant, rapid and sustained reductions in elevated levels of key biomarkers of inflammation and apoptosis that are implicated in the severity and progression of liver disease. Importantly, these key biomarkers are known to be elevated and to have prognostic value in multiple hepatic indications that Conatus is currently pursuing. The company's ongoing Phase 2 LC trial is evaluating emricasan's potential medium-term effect on liver function using two other potential surrogate clinical endpoints – Model for End-Stage Liver Disease (MELD) score and Child-Pugh-Turcotte (CPT) status. The company also is evaluating emricasan's potential longer-term effects on liver structure in its ongoing Phase 2b clinical trial in post-orthotopic liver transplant (POLT) recipients who have reestablished liver fibrosis or cirrhosis post-transplant as a result of recurrent HCV infection and have successfully achieved a SVR following HCV antiviral therapy (POLT-HCV-SVR). The company currently is developing a strategy for initial registration of emricasan as a potential treatment for patients with liver cirrhosis.
Pulmatrix, Inc. (NASDAQ: PULM) will report data from a Phase 1B study evaluating PUR0200, an iSPERSE formulation of a long acting muscarinic antagonist (LAMA) bronchodilator, on September 29th at the 2015 European Respiratory Society Congress. PUR0200 is being developed under the PK bio-equivalence pathway in Europe.
The two-part, single dose, placebo controlled dose-ranging clinical study in 38 patients was designed to evaluate the pharmacokinetics (PK), pharmacodynamics (PD) and safety and tolerability of PUR0200 compared to the reference product, a once daily LAMA bronchodilator. The main phase of the study was a 5-period crossover design with each patient receiving 3, 6, and 9 micrograms of PUR0200, 18 micrograms of the reference product, and an inhalation of placebo. PK results demonstrated that administration of PUR0200 resulted in dose proportional increases in plasma drug levels and all doses of PUR0200 improved pulmonary function compared to the placebo. Further, inhalation of PUR0200 3 micrograms resulted in similar PK and PD as the reference at a nominal dose that is 80% less than the reference product, demonstrating the delivery advantages of the iSPERSE™ technology. All doses of PUR0200 were safe and well tolerated.
Aduro Biotech, Inc. (Nasdaq:ADRO) today announced that Stephen T. Isaacs, chairman, president and chief executive officer of Aduro, will participate in an analyst led fireside chat at the Leerink Partners Immuno-Oncology Roundtable on Thursday, October 1, 2015, at 10:55 am Eastern Time. To access the live webcasts and subsequent archived recordings of the company's presentations, please visit Aduro's website at www.aduro.com.
Amyris, Inc. (Nasdaq:AMRS), the industrial bioscience company, today announced a multi-year, Technology Investment Agreement (TIA) worth up to $35 million with the Defense Advanced Research Projects Agency's (DARPA) Biological Technologies Office to create new research and development tools and technologies that will significantly reduce the time and cost of bringing new molecules to market. Amyris has chosen five specialized subcontractors to assist in achieving these innovations. "This agreement will foster the development of new bio-based manufacturing solutions that should position the U.S. as a leader in the development and deployment of biotechnology-based products. We're excited to be part of this transformation and are thankful for DARPA's support to pursue it," said John Melo, President & CEO of Amyris.
Argos Therapeutics Inc. (Nasdaq:ARGS), an immuno-oncology company focused on the development and commercialization of fully individualized immunotherapies based on the Arcelis® technology platform, today announced the appointment of Robert F. Carey to the company's board of directors. Mr. Carey will replace Mr. Jean Lamarre, who has served on the board since 2013, as a director and as chairman of the company's audit committee. Currently serving as executive vice president and chief business officer for Horizon Pharma plc, Mr. Carey has more than three decades of experience in healthcare investment banking, business development and investor relations. He has served as an advisor on greater than $15 billion in financings, as well as numerous mergers and acquisitions. He was also responsible for starting and managing JMP Securities' healthcare group. Mr. Carey holds a BBA in accounting from the University of Notre Dame.
The Association of periOperative Registered Nurses (AORN) will team with the Hill-Rom Surgical Division to present a national seminar series to help OR nurses better implement recently updated guidelines from the association. Attendees will include operating room directors, OR educators, OR staff nurses, and other health care professionals. The multi-city series kicks off in late September in New York City then moves to LA, Houston, Philadelphia and Chicago before wrapping up in Atlanta. AORN publishes and updates AORN Guidelines for Perioperative Practice to keep perioperative nurses informed and educated on evidence-based, best practices in the perioperative process. According to a recent survey of AORN member nurses, there was a need to have more tools to help implement those guidelines which include best practices in patient positioning.
Avinger, Inc., (NASDAQ:AVGR) a developer and manufacturer of image-guided, catheter-based systems for the treatment of peripheral arterial disease (PAD) and pioneer of the lumivascular approach to treating vascular disease, announced today that it has entered into a term loan agreement and a securities purchase agreement with CRG (formerly Capital Royalty L.P.). The agreements provide Avinger with new financing of up to $55.0 million. Under the terms of the term loan agreement, Avinger initially borrowed $30.0 million, which requires only interest payments for four years. Concurrent with this first tranche, CRG purchased $5.0 million in shares of the Company's common stock at a price of $14.357 per share. Avinger has the option under the term loan agreement to borrow an additional $20.0 million, in two tranches of $10.0 million each, at its discretion upon achieving certain milestones.
Hemispherx Biopharma (NYSE MKT:HEB) announced today a new peer reviewed article, with senior authors from the Italian Ministry of Health and other related agencies published in Clinical and Cellular Immunology: J. Clin Cell Immunol, 2015, vol 6:4 entitled, "A Toll-Like Receptor 3 – Agonist as Promising Candidate in Multiple Sclerosis Treatment." As stated in the Abstract of the article by the Italian authors: "The aim of this paper is to provide a brief overview of Ampligen® historical development, clinical pharmacology, clinical trials, and safety data and to discuss about its potential role in MS treatment in the context of existing treatment options." In the article, the authors observe that Ampligen®, an experimental therapeutic, unlike all other toll-like receptors (TLRs) studied to date, has a unique immune mechanism making it potentially adaptable as a treatment for many different disorders including multiple sclerosis (MS). They further state: "another winning point of TLR-targeting drugs is that they have fewer side effects and lower or no toxicity compared to other drugs used in MS treatment."
IPC Healthcare, Inc. (Nasdaq:IPCM), a leading national acute hospitalist and post-acute provider organization, announced today that it has acquired the psychiatry practice of Ashit K. Vijapura, M.D. The Tampa, Florida-based practice focuses on providing psychiatry services in both acute and post-acute settings. "We are pleased to welcome Dr. Vijapura and his team to the IPC family, as both acute and post-acute settings are increasingly seeing a need for quality behavioral health clinical programs. Dr. Vijapura's practice will expand our intellectual capital and capabilities in this important subspecialty area to another IPC market," said R. Jeffrey Taylor, president and COO of IPC Healthcare.
KemPharm, Inc. (NASDAQ:KMPH), a clinical-stage specialty pharmaceutical company engaged in the discovery and development of proprietary prodrugs, announced today that Sven Guenther, Ph.D., Executive Vice President of Research & Development, will be a featured presenter at the 9th Annual Pain & Migraine Therapeutics Summit being held September 23-24, 2015, in Washington D.C. In a presentation titled, "The Search for New Pain Therapeutics with Low Inherent Abuse Potential—A Case for Prodrugs," Dr. Guenther will discuss different approaches for finding new pain drugs with improved side effect and abuse profiles. Specifically, Dr. Guenther will highlight advances in the development of prodrugs and the progress of KemPharm's most advanced pain product candidates, KP201/APAP, a prodrug of hydrocodone in combination with acetaminophen, as well as KP511, a prodrug of hydromorphone. Dr. Guenther's presentation is scheduled for September 23, 2015, at 2:15 p.m., ET.
As the U.S. territories and Caribbean Islands wait for medical marijuana to make its debut, Medical Marijuana, Inc. (OTC Pink:MJNA) is proud to immediately offer residents an alternative: Real Scientific Hemp Oil [RSHO]™.
ProQR Therapeutics N.V. (Nasdaq:PRQR), a company dedicated to changing lives through the creation of transformative RNA medicines for the treatment of severe diseases such as cystic fibrosis and Leber's congenital amaurosis, today announced that Daniel de Boer, Chief Executive Officer, will take part in an analyst-led fireside chat at the Leerink Partners 4th Annual Rare Disease Roundtable on Wednesday, September 30, 2015 at 1:20pm ET. The conference is being held at Le Parker Meridien in New York, NY, USA. The live and archived webcast of the fireside chat will be accessible from the 'Investor Relations' section of ProQR's website (www.proqr.com) under 'Events and Presentations'. The archived webcast will be available for 30 days following the presentation date.
Rexahn Pharmaceuticals, Inc. (NYSE MKT:RNN), a clinical stage biopharmaceutical company developing best-in-class therapeutics for the treatment of cancer, today announced that Vikas Sharma, PhD, Director of Business Development, will present at the upcoming 15th Annual Biotech in Europe Forum for Global Partnering and Investment in Basel, Switzerland on Tuesday, September 29, 2015 at 9:20 a.m. (Central European Time). The 15th Annual Biotech in Europe Investor Forum for Global Partnering and Investment is recognized as a leading international forum for investing and partnering in the biotech and life science industry. The Forum draws together a cross-section of early-stage/pre-IPO, late-stage and public companies with leading investors, analysts, money managers and pharma licensing executives. Over 700 delegates and more than 120 presenting companies are expected to participate in this year’s Forum.
SAGE Therapeutics (NASDAQ:SAGE), a clinical-stage biopharmaceutical company developing novel medicines to treat life-altering central nervous system (CNS) disorders, today announced that Jeff Jonas, M.D., Chief Executive Officer, and Kimi Iguchi, Chief Financial Officer, will participate in an analyst-led fireside chat at the 4th Annual Leerink Partners Rare Disease Roundtable from 12:30 to 12:50 p.m. ET on Wednesday, Sept. 30 in New York City. The live webcast can be accessed on the investor page of SAGE's website at investor.sagerx.com. A replay of the webcast will also be archived for up to 30 days on SAGE's website following the conference.
Signal Genetics, Inc. (NASDAQ:SGNL), a commercial stage, molecular genetics diagnostic company focused on providing innovative diagnostic services that help physicians make better-informed decisions concerning the care of their patients suffering from cancer, today announced the signing of a Master Service Agreement (MSA) with a leading biopharmaceutical company. The first two projects under this MSA will deploy Signal's proprietary MyPRS® test to inform the clinical stage development program of a novel treatment – including potential combination therapies with current drugs – for patients with multiple myeloma. This is the second MSA Signal has entered into in 2015, and represents further validation of Signal's value proposition for the pharmaceutical and biotechnology industries. Signal and its newest biopharmaceutical partner will commence both projects prior to year-end 2015.
Stereotaxis, Inc. (NASDAQ:STXS), a global leader in innovative technologies for the treatment of cardiac arrhythmias, today announced the first procedures performed in the U.S. with its Vmotion suite of automation features. Cleared by the FDA this past June, Vmotion enables automatic orientation of a magnetically compatible Intracardiac Echocardiography (ICE) catheter in conjunction with the V-Sono™ ICE catheter manipulator. Widely used in the U.S., particularly with atrial fibrillation cases, the ICE catheter provides ultrasound imaging of the heart during electrophysiology (EP) procedures. The Vdrive™ with V-Sono system, released in the U.S. in 2013, remotely controls an ICE catheter in a Niobe® ES remote magnetic navigation enabled procedure. The V-Sono system can improve patient outcomes through more precise, stable ultrasound imaging and reduces radiation exposure to the EP team by eliminating the need for manual ICE manipulation within the radiation field. Vmotion supports the V-Sono manipulator functionality through three unique automation features: Spotlight, which continually keeps the ablation catheter tip within the ICE viewing plane automatically; Stored Positions, which allows for positions of the ICE catheter to be recalled and returned to throughout the procedure; and Sweep, which enables the ultrasound field of view to continuously sweep across an area of interest defined by the user.