MicuRx Taps China Links To Progress Improved Oxazolidinone
This article was originally published in PharmAsia News
Executive Summary
Multidrug-resistant bacteria have been identified as a major public health threat by the WHO. MicuRx, a Sino-US drug developer, is discovering and developing novel potential first-in-class antibiotics to combat such infections, and is taking an oxazolidinone with expected benefits over same class drugs into Phase III China trials.
SHANGHAI - After announcing positive top-line results from the first Phase II clinical trial with its next generation antibiotic MRX-I, Hayward, California-based MicuRx Pharmaceuticals Inc. plans to move forward by initiating Phase III trials this year in China.
The company’s lead drug candidate, MRX-I is an oral oxazolidinone antibiotic designed to treat infections caused by Gram-positive, multidrug-resistant bacteria such as methicillin-resistant staphylococcus aureus (MRSA) and vancomycin-resistant enterococcus (VRE), with better tolerability and safety profile compared to current oxazolidinone agents.
MicuRx received a composition of matter patent covering MRX-I from the US Patent and Trademark Office in 2012.
Backed by MicuRx’s joint venture with Shanghai Zhangjiang Biomedical Industry Venture Capital, the Phase II trial was designed to evaluate the safety and efficacy of MRX-I for a broad range of infections, including those that are multidrug-resistant.
“We expect to start a Phase III study in China later in the fourth quarter of 2015,” Zhengyu Yuan, president and CEO of MicuRx, told PharmAsia News.
“We are targeting multidrug-resistant Gram-positive bacterial infections,” Yuan said. “Because MRX-I addressed the key concern of the existing products, such as Zyvox and Sivextro, patients will have the choice of both oral and IV [intravenous] administration, short and long term therapy.”
Pfizer Inc.’s Zyvox (linezolid) is currently available for treatment-resistant bacteria but side-effects such as bone marrow suppression can occur after the two-week treatment period. Patients have to be monitored for leukocyte and platelet counts during therapy, which are difficulties with its use.
Zyvox, the lead oxazolidinone product, had worldwide annual sale of $1.3bn, Yuan noted.
Merck & Co. Inc.‘s Sivextro (tedizolid) is approved for acute bacterial skin and skin structure infections.
Clinical Data, Plans
According to MicuRx, data from two Phase I studies in China and Australia have confirmed that MRX-I was safe and well tolerated in healthy volunteers at all dose regimens, including a 28-day repeated dosing regimen alongside Zyvox as a comparator, with no evidence of myelosuppression that is typical for this class.
In the double-blind Phase II study conducted at 29 sites in China, patients with complicated skin and soft tissue infections received either 600mg or 800mg of MRX-I, or 600mg of linezolid, twice daily for a period of up to 14 days. For 178 clinically evaluable patients, both doses of MRX-I demonstrated a favorable safety and tolerability profile.
The clinical cure rates at the test-of-cure visit were 96.5% for the MRX-I 800mg group and 95.5% for the linezolid group.
“We believe MRX-I is the next generation of oxazolidinone antibiotic. Specifically, MRX-I addresses the key concerns of this class, namely myelosuppression and monoamine oxidase inhibition, while maintaining its antibacterial activity,” Yuan explained.
“We are exploring all possibilities to maximize shareholder value and the optimal pathway to bring our novel drugs to patients,” Yuan said when asked if the company plans to seek partnering opportunities for future trials and development.
It is difficult to recruit patients for antibiotic trials in China, as Chinese patients are generally reluctant to participate in clinical trials unless it is for a fatal disease. Given China’s slow regulatory process for clinical trials, several Chinese small to mid-size pharmaceutical companies have taken to conducting trials in Australia, such as BeiGene and Generon.
“We conducted the first trial for MRX-I in China, but later we also conducted a trial in Australia,” said Yuan. “Each geography has positives and challenges. We are pursuing a commercialization plan to address all geographies and are pleased to have completed our first Phase II clinical trial in China, with our second Phase II study ongoing in the United States.”
MicuRx received approval from the US Food and Drug Administration to initiate Phase II clinical trials in the US for MRX-I in March 2015.
Corporate Plans
With research and development facilities outside San Francisco and in Shanghai, MicuRx and Shanghai Zhangjiang Biomedical Industry Venture Capital announced to establish a joint venture in October 2012, namely Shanghai MengKe Pharmaceuticals, with the aim to advancing the development of MRX-I for the Chinese market.
Under the agreement, MicuRx will license all rights for development and commercialization of MRX-I to Shanghai Mengke in China. The joint venture expects to complete clinical trials and apply for marketing MRX-I in China by 2017.
MicuRx raised $25m in a Series B financing in 2013, led by BVCF, a private equity and growth fund specializing in the life sciences industry, the round also includes existing investors Morningside Group and Devon Park Bioventures. The financing will be used to fund the development of MRX-I in the US.
MicuRx has another antibiotic candidate, MRX-V, against Gram-negative bacteria, which is currently in the preclinical stage. MRX-V has a novel structure and mechanism with the potential to be a first-in-class drug, and shows better efficacy in treating resistant Gram-negative bacterial infections compared to aminoglycosides.