By Shannon Ellis, Staff Writer

SHANGHAI – Neuralstem Inc. has dosed its first patient with NSI- 566 stem cells, commencing the Phase I/II trial in China for ischemic stroke.

“We are excited to begin the first trial where the route of administration for our cells is injection into the brain,” said Karl Johe, chairman and chief scientific officer of Neuralstem, of Rockville, Md. “It is a crucial step forward for the company and the field at large, since optimizing cell therapy treatment for CNS indications will require delivering cells to the brain, as well as to the spinal cord.”

The trial is sponsored by Neuralstem’s wholly owned subsidiary, Suzhou Sun-Now Biopharmaceutical Co. Ltd., near Shanghai. All surgeries for the trial will be conducted in Bayi Brain Hospital, a Chinese military affiliated hospital in Beijing.

The patient was treated Dec. 27 and has returned home. Neuralstem’s CEO Richard Garr told Bioworld Asia, “Patient No. 1 is doing fine.”

This is the first time that Neuralstem’s stem cells, derived from the spinal cord, are being transplanted directly into the brain. The procedure makes use of a fairly routine stereotactic injection to place the stem cells near the stroke lesion.

The Chinese partners see this international collaboration as a step in pushing capabilities here to the forefront of new neurological paradigm.

“We are glad to be part of this world-leading clinical research project,” said Ruxiang Xu, chief physician at Bayi Brain Hospital.

The Phase I trial will seek to find the maximum safe-tolerated dose for NSI-566 testing six cohorts of three patients each. With each cohort the dosing will increase. Trial subjects displaying chronic residual motor disorders will be enrolled between four and 24 months from when strokes occur. After the results are in from the first 18 patients, Phase II will recruit and test another 100 patients.

Neuralstem’s NSI-566 stem cells are expected to repair damaged neural circuitry and promote repair and recovery. The need for such a treatment is great. China has the largest number of stroke victims in the world. It’s estimated that 1,1750,000 survive a stroke annually.

Ischemic stroke occurs when the blood supply to the brain is interrupted by an obstructed blood vessel.

It is the second most frequent type of stroke in China, after intracerebral hemorrhage. Strokes are a major cause of death and disability in the U.S. and China.

Phase II will be a multi-site, randomized and blinded study with a control group. Half the patients will receive the one time NSI-566 stem cell treatment with physical therapy. The other half will receive physical therapy only. Follow-up measurements will also be blinded. The trial is expected to take two years.

China and Stem Cells – A Potent Mix

China is known for its questionable medical tourism in stem cell treatments. Dozens of hospitals advertise stem cell treatments for cerebral palsy, Alzheimer’s and brain injuries to name just a few.

Although constantly reforming, the country has fewer regulations and looser enforcement than many Western countries.

With so many hospitals providing treatments, China also has been criticized for not consistently meeting international standards of clinical trial documentation in this area.

“They have a different mindset about stem cell medicine,” said Garr, when asked to explain China’s forward stance towards the experimental therapy.

“China has long been very aggressive in allowing different stem cell technologies to be used in trials and treatments. Becoming a leader is not only about allowing programs to move forward in humans, but it is an important factor. There are regulatory hurdles to be sure, but no cultural bias against stem cell science that will slow down progress,” said Garr.

Neuralstem is confident in its choice of partner, Bayi Brain Hospital, to conduct the Phase I/II trial for ischemic stroke for the first time. It says it has been able to maintain the standards of their existing U.S. trials to “create equivalent quality.”

The trial kicks off a relationship between the Chinese hospital and Neuralstem that has been nurtured since their MOU in 2011.

“Certainly there is always skepticism about many clinical trials conducted out of the usual U.S./European axis,” said Garr. “We are using a protocol we developed to use in the U.S. next, and of course the 566 cells are currently being used in FDA approved trials in the U.S. We use the same quality controls and protocols for expansion.”

Neuralstem established the Suzhou facility in 2010 to grow the cells for the trials in a Chinese approved cGMP manufacturing facility. It is following the same transplantation methods used in the U.S., which require thawing of the cells and quality control before overnight shipping to the surgery site.

“We are using the same protocols in China, so having local manufacturing and distribution is necessary,” explained Garr. “We actually send our own U.S. scientists over to do the manufacturing steps, but also have a local/on site team, fully trained by us, for final fill and QC for individual surgeries.”

The NSI-566 stem cells are fetal-derived neural precursor cells derived from one single tissue source donated in 2000. Neuralstem cell expansion technology will allow it to have adequate supply from the one cell line for all the spinal cord indications it is exploring: ALS, spinal cord injury as well as stroke motor deficits.

NSI-566 are the same cells that Neuralstem has had approved for ALS trials in the U.S. for which it has been awarded orphan status designation by the FDA. (See BioWorld Today, Jan. 6, 2014.)

China Approval First?

The time Neuralstem has taken in China to set up manufacturing and the clinical partnership with Bayi appears to have given the company crucial insights into what it takes to navigate the Chinese approval process.

In a statement Neuralstem pointed out that China has different regulatory paths to commercialization, which it plans to pursue simultaneously, “to harmonize a Western style of discipline and care with existing traditions and the commercialization culture” of China.

Garr expanded, saying, “the centralized Chinese FDA system is evolving and maturing. There are many provincial entities that still retain various abilities to approve and deliver medical products to their citizens. The military and police hospitals also retain some autonomy in various areas. The continuing balance between these different authorities is a subject of continual change, a work in progress so-to-speak.”

Neuralstem is not in the game of using China as a cheap place for trials with an eye to global markets, but sees China as the big prize itself.

Garr recognizes each regulatory agency will look at the data from the trials from their own unique perspectives.

“What is critical to understand, is that while we do expect to be able to use this data around the world, that is not why we are in China,” Garr said.

“There is a myopia in the Western world about Asian markets, despite their obvious size, and growing population of patients with an expectation of world-class, cutting-edge medical care. But we look at it differently. We don’t ask, ‘How can you operate your business in China?’ We ask, ‘How can you not?’”

©2014. REPRINTED WITH PERMISSION FROM THOMSON REUTERS.