Cutting-edge drug pioneer goes to new battlefield

Hepeng Jia/Beijing, China

Gene therapy pioneer Hu Fang is launching a new venture - a company using an miRNA-based approach to develop anti-influenza medicine.

’I believe the new venture will give the chance of a new beginning, both for me and for innovative gene therapy in China,’ Hu told Chemistry World.

As the developer of the world’s first commercialised oncolytic virus-based gene therapy medication, H101, which uses a genetically modified virus to selectively kill tumour cells believed to have a dysfunctional P53 gene, Hu’s life has been closely tied to the up-and-downs of China’s biotech industry. It has been a long, hard struggle; although successfully overcoming Western competition, there were often less than successful returns from the market. 

Starting from scratch

Hu started his medical career as a barefoot doctor working in the countrywide in the remote northwestern Chinese province of Heilongjiang. After postdoctoral work at the University of California in San Francisco (UCSF), US, Hu returned to China in 1995.

In 1997, San Francisco-based Onyx Pharmaceutical began to develop a gene therapy based on the oncolytic virus, called Onyx-015. Hu found that Onyx had not obtained a patent for its Onyx-015 project in China and immediately applied for such a patent.

Hu’s team started almost from scratch, before being granted funding from the State-owned, Hong Kong-listed Shanghai Industrial Holding Company. He restructured the company of which he was then president, Sunway Biotech, to support the ongoing oncolytic project, and closely followed developments at Onyx as it quickly completed early trials of the gene therapy. 

Just as the second phase of Sunway’s H101 clinical trials achieved satisfactory results, Onyx announced that it would not be launching Phase III clinical trials of Onyx-015 due to a lack of money. 

’I knew Onyx must be less confident about subsequent trials of its medicine, because if a promising drug has satisfactory enough results in the first two phases of clinical trials, it should be easy to obtain funding,’ Hu says. 
Hu knew his research also ran the risk of failure, but remained confident because of the good clinical results his team had obtained. 

Sunway Biotech launched Phase III clinical trials of H101 in late 2002. By November 2005, the treatment had been granted a license under the brand name Oncorine, after showing good efficacy in eliminating or reducing tumour cells in patients suffering from nasopharyngeal cancer (NPC), a head and neck cancer prevalent in China.

New challenges

Despite opposition from some of his colleagues, Hu insisted on buying the patent for the failed Onyx-015. In doing so, Sunway became one of the few Chinese firms to hold the global patent of a totally new drug.

Although Hu insists that the drug should be launched to an international market, the path is not easy.

In China, Oncorine’s sales are not satisfactory at just several millions yuan - far less than a potential blockbuster should achieve.

Hu attributes this to the intra-tumour injection used to administer Oncorine. The technical challenges associated with this mode of treatment have made Chinese doctors and nurses reluctant to use the new therapy.

Another challenge lies in the limited number of NPC patients. There are about 30,000 to 40,000 new NPC patients in China each year, but most opt for surgery plus chemotherapy instead of using the expensive Oncorine.

’But there is hope for Oncorine because of sound scientific evidence,’ says Hu. ’The key is to launch new clinical trials for new cancers to expand its indications."

But Hu’s investor - Shanghai Industrial Holding - ran out of patience, and late last year, Hu left Sunway Biotech. 

Looking into future

’China’s biomedical entrepreneurs face the biggest challenge worldwide. They have to conduct research, commercialise their research, seek funding from scratch, manage the company, learn to persuade cautious regulators, and eventually conquer a market which they are not familiar with,’ Hu says.

But he is confident, saying his new venture, an miRNA approach to develop anti-influenza treatments (funded by the Ministry of Health and Suzhou Life Science Park), has been inspired by his long experience in developing gene therapy drugs. 

According to Hu, most efforts to develop miRNA-based treatments are focused on a tumour, but this can be a tricky target to hit. 

On the other hand, the biggest challenge for flu medicine is the virus’ continued mutation.

’Before a new drug can be used, safety concerns much delay its development, so that we are always one step behind the viral mutation,’ Hu told Chemistry World.

But the toxicological effects of miRNA mainly lie in whether it can match with human genome. If a section of miRNA is found to have curative effects against new flu virus, people can analyse its toxicological effect beforehand by using computer-based methods. 

’In this way, the time-consuming toxicological experiments could be reduced in emergency situations such as a pandemic flu outbreak,’ Hu says. ’In this way, the development stage can be largely reduced.’

Hu’s new company is expected to finish the pre-clinical work on the new miRNA approach next year.

’With my expected success, I will achieve my dream of taking innovative Chinese medicine to lead the world,’ he says.