China’s Gene Therapy Cancer Drugs: Slow Acceptance of Great Science

In a recent article, Bloomberg profiled Shanghai Sunway Biotech Co., detailing the career path of its founder, Dr. Hu Fang. The article uses the highly picturesque image of Hu’s career beginnings as a “barefoot doctor,” ordered at age 19 to the provinces to tend the rural population during the Great Leap Forward of the 1960s, sent without the benefit of medicines or instruments.

Now, his career having advanced greatly, Hu heads a leading edge biotech company, one that has brought gene therapy to cancer drugs. In between, Hu received his MD from Herbing Medical University and a PhD from Shanghai Second Medical University, and then studied liver disease at the University of California San Francisco. Hu’s remarkable story serves as an apt illustration of the astonishing Great Leap Forward of China biotech in the last 15-20 years. The history of gene therapy, meanwhile, has been told often: once considered the next big thing in the West, hope for gene therapy quickly dissipated when an 18-year-old patient in Pennsylvania unexpectedly died during the first clinical trial in 1999. Seeing huge clinical roadblocks, biotech moved on to more promising, less dangerous areas of research.

Meanwhile, in China, scientists continued working on proving the effectiveness of gene therapy drugs. Clinical trials using gene therapy for such diseases as multiple dystrophy and Parkinson’s disease are now getting underway in the US. Part of the reason China kept investigating the technology for cancer was its need for an effective treatment of head-and-neck cancer, which is much more prevalent there, comprising 10% of the 2.5 million new cases of cancer that are diagnosed each year.

In China (and in Chinese from the Southern area who now live in the US), nitrites in the salt used on fish seem to be the cause of the cancer. In US Caucasians, smoking is the usually cited culprit for the relatively small number of head-and-neck cancer cases. The clinical success of China’s cancer gene therapies, however, has not translated into an equally impressive commercial triumph.

At the moment, there are exactly two approved gene therapy drugs in China, both indicated for head and neck cancer: Gendicine from SiBiono, which is in turn majority owned by US listed Benda Pharma (BPMA.OB), and Oncorine from Shanghai Sunway Biotech, which is not publicly listed, but is 73% owned by Mergen Biotech, a maker of DNA microarrays located in the San Francisco area.

In its pivotal clinical trial, Sunway’s drug Oncorine, known also as H101, was given as an adjunct to chemotherapy. Oncorine increased the percentage of patients who experienced a clinical response (either partial or full tumor shrinkage) from 57% with chemotherapy alone to 76% for patients who received both. A significant increase, though not a magic bullet. However, for approval in the West, there were problems in the design of the trial, starting with the small number of patients enrolled in the trial. The pivotal test included just 123 patients, too few for Western standards.

Moreovoer, shrinking a tumor does not necessarily translate into greater survival. Plus, China allowed interaction between Oncorine patients and Sunway officials, something that would not be countenanced in Western trials. Dr. Hu visited patients and suggested modifications to patients’ regiment, depending on how the response was proceeding. Any one of these three factors would be enough to disqualify the results for FDA approval.

Sunway has not published results on long-term survival for Oncorine, though this summer SiBiono/Benda did release five-year data on Gendicine. Out of 26 patients who received Gendicine and radiotherapy, 17 have survived for 5 years, 16 of them without any recurrence of their cancer. In the control group of an almost equal 27 patients, 14 survived to the five-year mark, but only 10 remain cancer-free. These data are positive for Gendicine, but like the Oncorine results, they fail to reach the level of statistical significance because they suffer from a too-small sample size.

Earlier this fall, SiBiono/Benda reported a big sale of Gendicine after the company held a seminar for doctors showing its effectiveness and teaching doctors how to administer the drug. On behalf of their hospitals, the doctors ordered $3.8 million worth of the drug, forcing SiBiono/Benda to increase production to meet the demand. The company said it expected to fill the order before the end of the year. While the order is significant, it is equally significant that Benda reported an under-$4 million sale as an important event in its corporate history. Benda reported $16 million in revenue for the first nine months of 2007, much of it from products other than Gendicine.

As a private company, Sunway does not release data about revenue, but it has admitted that it, too, has been disappointed in the initial sales of its cancer gene therapy (Gendicine was approved in 2004; Oncodine in 2005). To help raise income, Sunway also has a genetically engineered protein drug, rhG-CSF (recombinant human granulate-colony stimulating factor) on the market. In addition, Sunway is continuing to investigate two other gene therapy drugs: H102 for liver cancer and H103 for solid-tumor cancers. It also is seeking treatments for non-small cell lung cancer.

In addition, Sunway recently signed a collaboration with Genzyme (GENZ) to win approval and distribute in China the experimental gene therapy drug Ad2/HIF-1a, a drug that seeks to grow new blood vessels in patients with peripheral arterial disease. Sunway will manufacture the drug in China and undertake the trials necessary to win marketing approval in China from the SFDA. As another gene therapy biotech drug, Ad2/HIF-1a fits nicely into Sunway’s portfolio. The China advances in gene therapy against cancer may have not rewarded their companies with financial success, and unfortunately, lingering doubts about the objectivity of the clinical trials have not quieted skeptics of the technology in the West. Nevertheless, the ability of China to succeed in finding drugs that use gene therapy to fight cancer is a strong symbol of China’s technical prowess in biotech.

Disclosure: none.