Universal CAR-T Movement in Full Swing in China

Universal CAR-T Movement in Full Swing in China

China’s immune-oncology sector is not only catching up to the West (U.S. & Europe) but perhaps even surpassing it when it comes to cranking out powerful immunotherapy faster at more economical prices. This offers more access to those battling deadly cancers.  Gracell Biotechnology Ltd. represents a case in point—the startup has developed a CAR-T therapy that saved a working-class teenage boy’s life. The Universal CAR-T movement is in full swing in China.

The Healing of Zhang Haitao

A teen from a working class family in the rural, southwest Sichuan province, dreamed of a specialized basketball school. A pain in his right arm changed his life—it led the teen down a path familiar to most cancer patients—many hospital visits, tests and multiple chemotherapy rounds. 

Ultimately, his doctor suggested an experimental gene therapy offered in clinical trials by a Chinese startup known as Gracell biotechnology Ltd. Zhang spent a few weeks in the hospital where the research team removed white blood cells from his body, genetically engineered them and infused them back into his body. A month later, Zhang’s bone marrow revealed his body was clear of cancer. He visited the Chinese city of Chongqing several months later for a series of tests: he remained cancer-free. In response to his situation now, Zhang noted to local Chinese press, “It seems like a new solution that will give people hope.”

Is China becoming the CAR-T Therapy Research Capital?

Although CAR-T therapy was first developed by Zelig Eshha, an Israeli scientist back in the 1980s, it has been significantly advanced by U.S. and European research centers and biopharmaceutical companies, reports Business Mirror. But China will seek to take the science and commerce to the next level—and this makes sense as it has the largest population and perhaps the fastest and largest-growing cancer patient population. It is no secret that central planners in China seek to make China a technology and life sciences super power—this is evidenced everywhere nowadays. Nowhere is the science of biotech—from CRIPSR-based gene editing to cell and gene therapy development—pushed as hard to its limits, and perhaps dangerously so. After all, China is home to the world’s largest cancer population and some of the most advanced experiments. It has a population to take care of, and income distribution and health access unfolds in such a way that perhaps it has no choice but to become the nexus of CAR-T research.

Chinese Innovation could Beat the Competition

Although Novartis and Gilead Sciences have been commercial leaders in marketing CAR-T therapy since 2017, the treatments are extremely expensive. Also, the process of engineering CAR-T therapies (e.g. working with the patient’s white cells, replacing them and infusing them back into the patient) can take time, and in China, many patients with more aggressive cancers could die waiting for treatment.

Hence, Gracell’s approach is revolutionary. Instead of the weeks for treatments to be engineered—such as is the case with American and European drug makers—the Shanghai-based venture is churning out cancer-killing immune cells overnight!

Moreover, their price points for cancer patients are far cheaper. After all, the Chinese market is large and many won’t be able to afford western prices. Hence, Gracell has come up with a genetic engineering process that accelerates the cell production stage, reports William Cao Wei, founder of Gracell. In fact, Gracell will sell its CAR-T treatment for about 500,000 yuan or about $71,000—a deep cut from the $475,000 Novartis charges for its comparable treatment Kymriah. Gilead’s similar treatment costs $373,000.

Chinese CAR-T Ventures well Positioned to Capitalize on Exploding Market

With China’s already massive population (largest in the world) and rapidly aging demographic—not to mention lifestyle changes as the population has become richer, an explosion of cancer diagnoses is expected—more new cancer patients emerge in China than anywhere else worldwide. The central government has made it policy for the country to become a scientific superpower and to dominate the field of genetics, for example. Hence, Gracell and other Chinese startups are moving full throttle toward commercialization and widespread use by next year. According to IQVIA Institute, the stakes are big—the present market for cancer treatments approaches $133 billion per annum. Gracell’s founder Cao reports, “there will definitely be competition.”

Loosening Regulatory Framework in Quest to be Scientific Superpower

In a bid to leave the competitive pack behind (and help its people), China central government authorities now consider the “loosening up” of its regulatory framework for advanced classes of therapy, such as CAR-T therapy. In a move to infuse decentralized dynamism in the clinical research and drug development paradigm, authorities seek to empower regional academic ethics committees within health providers (e.g. hospitals) to approve new CAR-T treatments. And after they approve them, they will be afforded the authority, potentially, to market and administer these services to patients for a fee. Today, the Chinese regulatory regime is comparable to the U.S. and Europe, and this approach would be a somewhat radical departure. This has scary potential for abuse and conflict of interest.

In fact, these changes are part of a President Xi Jinping’s broader, ambitious campaign for world scientific domination. The contemplated regulatory changes represent danger for many experts. For example, Tao Xin, a Washington D.C.-based lawyer at Hogan Lovells LLC, specializes in healthcare regulatory law in both America and China. He notes that it would be difficult to assure that localized hospital committees in China possess the qualifications to evaluate and approve such complicated therapies.

Some Disturbing Cases

After all, if providers—whether in China or America—have the power to approve drugs and then sell them at a profit, ethical considerations could ensue. From patient safety to conflict of interest, the red flags are waving.  For example, back in 2016, a 22-year-old college student died when being treated for synovial sarcoma with a failed experimental cell therapy at a Beijing hospital. In seeking to point out a real wrong, the hospital had falsely advertised the treatment’s effectiveness on a boy via a Baidu ad that made it look like a legitimate and truthful statement. There is sufficient evidence to conclude that false advertising could have been associated with the young man’s death.

In another incident last year at a hospital in the eastern city of Xuzhou, the provider was sued after a patient with lymphoma died from a CAR T therapy treatment.

Venture Capital Floods into Chinese Biotech

Money is flooding into Chinese biotech, reports Business Mirror. Venture capital investment has quadrupled in growth from 2015 till now—where $17.6 billion poured into Chinese biotech just last year, reports consultancy ChinaBio LLC

The money comes from everywhere—just take Gracell, where it has raised funds from Singapore’s sovereign wealth fund Temasek, Lilly Asia Ventures and others. Gracell reports that of the 35 patients that have enrolled in its China-based clinical trials, 32 have gone into complete remission—an incredible record if true. These data points stimulate the frenzy for even more investment.

Other ventures that are developing similar treatments include Nanjing Legend (part of Hong Kong listed Genscript Biotech Corp., and U.S.-listed Cellular Biomedicine Group Inc.). Novartis invested $40 million for a 9% piece of Cellular Biomedicine. Novartis will use their cell therapy to make its Kymriah therapy, currently under review for approval in China. Biotech ventures such as Cellular Biomedicine are digitizing and automating processes to condense cell engineering time from four weeks to less than 10 days.

The Next Frontier: CAR-T for the Masses

China is on a mission to make CAR-T as accessible as any other drug, and Chinese startup ventures appear to be taking a lead position in pursuing this cause. In fact, the “universal CAR-T” movement is in full swing in China. What does this mean? Finding a way to take T-cells from healthy people and engineering them so that they can be infused into any cancer patient.