Legend Biotech's CAR-T Therapy Cilta-cel Gains FDA Approval, Marking a New Milestone for Chinese Innovative Drug Globalization

Domestically producedHalf a month after the PD-1 inhibitor’s initial setback in its bid to enter the U.S. market, cell therapy achieved a breakthrough in global expansion: cilta-cel, the CAR-T product co-developed by Legend Biotech and Janssen, received FDA approval in the United States.

Industry insiders quickly drew parallels between Cilta-cel and BeiGene’s anticancer drug, zanubrutinib. This marks a “new milestone” following zanubrutinib’s historic achievement in November 2019, when it became the first Chinese-developed new drug to gain approval overseas, breaking the “zero breakthrough” barrier for Chinese innovative drugs going global.

Following Innovent’s overseas expansion case, this positive news carries particular significance.

Of course, the most critical question is: Why did the PD-1 collaboration between Innovent and Eli Lilly fail, while Legend Biotech and Janssen’s CAR-T therapy successfully expanded overseas?

As recently as last November, Cilta-cel’s global expansion hit a snag when the FDA extended its review timeline by three months.

Although the official reasons have not been disclosed, industry insiders speculate that it is likely related to the need for further improvements in the product's manufacturing process, requiring the submission of additional documentation.

In retrospect, this was merely a minor setback on the path to approval. Industry insiders largely believe that the U.S. approval of Cilta-cel is only a matter of time. This success once again underscores that clinical data are the most critical factor in the global expansion of pharmaceutical products.

Following the Innovent case, subsequent analyses have frequently drawn comparisons with the global expansion of zanubrutinib. Much of the discussion has centered on shifts in the FDA’s review and approval paradigm, particularly whether these changes were influenced by political factors.

For now, these skeptics can rest assured. “The FDA’s review is still fundamentally based on scientific evidence. While there may be some radical or conservative viewpoints, a mainstream consensus tends to emerge internally over time,” a senior executive at a well-known Chinese CRO told VCBeat New Medicine. “Political factors may also play a role, but they will not overturn the most basic principle of scientific rigor.”

In terms of clinical data, Cilta-cel has demonstrated remarkable efficacy, capturing significant attention at the 2017 ASCO Annual Meeting. At that time, Legend Biotech’s R&D team reported an impressive 100% overall response rate in patients with multiple myeloma.

The release of these impressive figures directly led to Janssen paying Legend Biotech an upfront cash payment of $350 million in December 2017, as the two parties entered into a collaboration to jointly develop this anticancer drug. Five months later, they obtained Investigational New Drug (IND) approval from the U.S. FDA and successfully commenced Phase Ib/II clinical trials.

In trials conducted in the United States, the efficacy of Cilta-cel was confirmed. Long-term results from the Phase Ib/II CARTITUDE-1 study, released last December, showed an overall response rate of 98%.

Currently, the United States has only one approved BCMA-targeted CAR-T product, Abecma, which was approved approximately one year earlier than Cilta-cel. However, Legend Biotech and Janssen believe that long-term clinical data demonstrate their competitive advantage.

“Its clinical value has been demonstrated, and to some extent, it has addressed unmet medical needs in the U.S. market,” Dr. Guo Xiaoning, Vice President, Head of R&D, and Chief Medical Officer at SciClone Pharmaceuticals, told VCBeat New Medicine. Dr. Guo has many years of experience working at multinational pharmaceutical companies such as Johnson & Johnson and AstraZeneca, where he led multiple global drug development programs.

Furthermore, industry analysts note that although Innovent and Legend Biotech have respectively partnered with two multinational pharmaceutical companies, Eli Lilly and Janssen, their collaboration models differ significantly. “Legend’s strategy is to first seek marketing approval in the United States, and then reintroduce the product into the Chinese market.”

An industry insider observed that in the Cilta-cel project, a collaboration between Legend Biotech and Janssen, Janssen took the lead while Legend Biotech primarily assumed supportive and execution roles, focusing its main efforts on the subsequent R&D of its CAR-T pipeline. “Janssen boasts strong capabilities in both clinical resources and its understanding of FDA regulations.”

Yesterday morning, news of the approval broke. In a group chat of industry professionals, discussions were lively, with over 90% of insiders expressing highly positive sentiments.

It can be said that the news of Legend Biotech’s successful overseas expansion has, to some extent, boosted the sagging morale of China’s biopharmaceutical sector.

Cell and gene therapies, represented by CAR-T, have emerged as a new frontier in cancer treatment following PD-1 inhibitors, bispecific antibodies, and antibody-drug conjugates (ADCs), attracting significant capital inflow into the industry. However, momentum in this sector has cooled over the past two years. Legend Biotech’s successful international expansion is likely to reinvigorate interest in this field.

“As the first domestically developed CAR-T cell therapy to receive FDA approval, it at least demonstrates that a CAR-T product developed by a Chinese enterprise can achieve commercial success in the market,” said the senior executive of the aforementioned well-known CRO company. “The capital markets may interpret it this way. Therefore, investment and financing activities in the CAR-T sector could become even more vigorous than before.”

Currently, the two CAR-T products approved in China have both been introduced through Sino-foreign joint ventures. Given the regulatory specifics of cell therapies, the Center for Drug Evaluation (CDE) places significant emphasis on the FDA’s approval history.

It is not difficult to predict that many cell therapy developers will choose to seek regulatory approval abroad first, before pursuing approval in China. Going global may become an essential strategic option they must consider.

Not long ago, Innovent Biologics and Gracell Biotechnologies jointly announced that the U.S. FDA had officially granted Orphan Drug Designation to their co-developed fully human autologous B-cell maturation antigen (BCMA) chimeric antigen receptor T-cell (CAR-T) injection for the treatment of relapsed/refractory multiple myeloma.

Thus, the collaboration between Legend Biotech and Janssen has also charted a clear course for subsequent companies seeking to expand overseas.

Going global is only the first step; the next moves by Legend Biotech and Janssen, particularly their commercialization strategy in the U.S. and the timing for seeking domestic approval in China, are equally drawing significant attention.

Legend Biotech and Janssen are preparing to launch Cilta-cel “immediately.” “We are ready,” Legend Biotech CEO Ying Huang told the media on Monday, noting that the company has already hired a sales and marketing team. Notably, the drug will be priced at $465,000, slightly higher than the $419,500 price tag for Abecma.

Beyond the U.S. market, industry insiders largely believe that Legend Biotech will also actively seek domestic approval in China, thereby exporting first and then selling back into the Chinese market.

Under the agreement, Legend Biotech and Janssen will share profits and costs on a 50/50 basis in regions outside Greater China, and on a 70/30 basis within Greater China.

An industry insider, who recently communicated with personnel from Legend Biotech, sensed that the other party exhibited a determined attitude to secure success.

“Although there have been no updates on domestic R&D progress, no BCMA-targeted CAR-T products have been approved for marketing in China so far. Products in the BCMA pipeline are all at very early stages, with most having only obtained approval for registration-based clinical trials and remaining in Phase I clinical trials. Therefore, Legend Biotech holds a significant advantage.”

And a successful overseas launch will undoubtedly accelerate the domestic approval of Cilta-cel.