Novartis' CAR-T Therapy Kymriah Approved in Japan: How Close Is China?

In late last month, the news that Japan was about to approve Novartis’ CAR-T therapy Kymriah for market launch sparked widespread discussion among industry professionals and the general public. Recently, Japan’s Ministry of Health, Labour and Welfare (MHLW) officially approved Kymriah for the treatment of CD19-positive relapsed or refractory (r/r) B-cell acute lymphoblastic leukemia (ALL) and CD19-positive r/r diffuse large B-cell lymphoma (DLBCL).

Undoubtedly, this approval will further expand the global reach of the CAR-T therapy Kymriah. Kymriah is the first CAR-T therapy to date to receive regulatory approval in Asia for the aforementioned two B-cell malignancies. The approval of Kymriah in Japan also marks a milestone for Kobe BioMedicineAfter the Foundation for Biomedical Research and Innovation (FBRI) successfully completed the technology transfer for the clinical production of Kymriah.

Kymriah is a living drug product manufactured individually for each patient by reprogramming their own immune cells. Its approval for marketing in Japan aligns with authorizations granted by regulatory authorities in the United States and Europe. The Ministry of Health, Labour and Welfare (MHLW) reviewed data from the global registrational CAR-T clinical trials JULIET and ELIANA, which also included studies conducted in Japan. In these trials, Kymriah demonstrated robust and durable response rates along with a consistent safety profile in the two aforementioned difficult-to-treat patient populations.

How Far Has the CAR-T Therapy Kymriah Come?

To date, Kymriah has been approved by regulatory authorities in the United States, the European Union, and Canada.

In 2018, the sales of both marketed CAR-T products failed to meet expectations; however, compared to Yescarta's full-year sales of $264 million in 2018, Kymriah's full-year sales amounted to only $76 million.

This is largely due to manufacturing issues at Novartis. Novartis is making every effort to bolster its manufacturing capabilities, including the acquisition of Cell for Cure, Europe’s largest cell and gene therapy manufacturer, and entering into a manufacturing agreement with Cytopeutics regarding potential approval in the Chinese market. Susanne Schaffert, CEO of Novartis Oncology, stated that manufacturing capacity is now planned to increase fourfold.

01

United States

In August 2017, the U.S. FDA approved Kymriah for marketing, for use in patients aged 25 years and younger with B-cell acute lymphoblastic leukemia (B-ALL). This was a historic milestone.

Subsequently, in October 2017, the FDA approved another CAR-T product—Yescarta (Gilead/Kite Pharma)—for the treatment of adult patients with relapsed or refractory large B-cell lymphoma.

In May 2018, the FDA approved a second indication for Kymriah, the world’s first CAR-T therapy—relapsed or refractory large B-cell lymphoma.

Pricing and Medical Insurance Aspects

Undoubtedly, high pricing is a significant aspect reflecting the transformative nature of these innovative therapies. In the United States, Kymriah is priced at $475,000 for B-cell acute lymphoblastic leukemia (B-ALL) and $373,000 for large B-cell lymphoma, while Yescarta is priced at $373,000.

On August 2, 2018, the Centers for Medicare & Medicaid Services (CMS) released the final rule for the Inpatient Prospective Payment System (IPPS) for fiscal year 2019, which included reimbursement for CAR-T therapy. Effective October 1, 2018, CAR-T therapy was classified under Autologous Bone Marrow Transplant with CC/MCC or T-cell Immunotherapy (MS-DRG 016). Patients are required to pay a base amount of $36,000, plus a New Technology Add-on Payment (NTAP) of up to $186,500.

Finally, on February 15, 2019, the CMS officially released the Proposed Decision Memorandum: approving the inclusion of CAR-T cell therapy in Medicare coverage!

02

European Union

Last August, the European Commission approved two CAR-T therapies on the same day: Novartis’ Kymriah and Gilead’s Yescarta.

United Kingdom

Less than ten days after the EMA approved its market launch (on September 5, 2018), the NHS had already reached a reimbursement agreement with Novartis for Kymriah, marking the first time a European country agreed to fund CAR-T therapy. Two months later (on November 16, 2018), NICE recommended Novartis’s Kymriah for young patients with relapsed or refractory B-cell acute lymphoblastic leukemia (B-ALL), enabling these patients to access Kymriah treatment through applications to Novartis via the Cancer Drugs Fund (CDF).

On December 7, 2018, NICE issued its final draft guidance, recommending Gilead/Kite Pharma’s Yescarta to the CDF.

On February 1, 2019, NICE announced that adult patients with relapsed or refractory DLBCL could access Kymriah through the Cancer Drugs Fund (CDF).

In mid-February, the Scottish Medicines Consortium (SMC) approved Kymriah for inclusion in the Scottish NHS for patients aged under 25 with relapsed or refractory B-cell acute lymphoblastic leukemia (B-ALL), stating that a confidential discount made it “an acceptable use of the limited resources of the Scottish NHS.” Furthermore, the agency will make decisions on other approved indications for Kymriah in March this year.

Recommended Reading:

Finally! The UK’s NHS officially covers Novartis’ CAR-T cell therapy drug Kymriah; individuals under 25 can apply for treatment through the CDF | MedTrend Exclusive

03

Canada

In September 2018, Health Canada approved the country’s first CAR-T therapy, Kymriah, for the treatment of pediatric and young adult patients aged 3 to 25 years with relapsed or refractory B-cell acute lymphoblastic leukemia (B-ALL), as well as adult patients with relapsed or refractory large B-cell lymphoma.

In January 2019, an expert panel convened by the Canadian Agency for Drugs and Technologies in Health (CADTH) reported that Kymriah should be publicly funded if the manufacturer reduces its price, a move that could cost the Canadian healthcare system more than $400 million over three years.

In China, as early as April 2017, Shanghai FosunPharmaceuticalsThe Group established a joint venture with U.S.-based Kite Pharma in Shanghai, China — Fosun Kite.

On September 3, 2018, the Investigational New Drug (IND) application for FKC876 (U.S. trade name Yescarta) was officially approved for clinical trials by the National Medical Products Administration. Fosun Kite has obtained full technology licensing from Kite for this product and holds commercialization rights in China, including Hong Kong and Macau.

Novartis has entered into a strategic partnership with Cytopeutics, whereby Cytopeutics will be responsible for the production and supply of Kymriah in China, while Novartis retains the exclusive marketing rights for Kymriah.

Furthermore, CAR-T immunotherapies from Legend Biotech, JW Therapeutics, Galaxy Biopharma, Hengrui Dasheng, Carsgen Therapeutics, and Chongqing Precision Biotechnology have received clinical trial approval in China, with multiple companies having submitted Investigational New Drug (IND) applications for their CAR-T candidates to the National Medical Products Administration. According to ClinicalTrials.gov, more than 200 CAR-T clinical trials (including investigator-initiated trials) are currently underway in China, underscoring the intense momentum in research and development.

How Far Is China from the Market Launch of CAR-T Therapy?

Reference:

https://www.globenewswire.com/news-release/2019/03/26/1767526/0/en/Oxford-Biomedica-notes-the-Japanese-approval-of-Kymriah-tisagenlecleucel-the-first-CAR-T-cell-therapy-authorised-in-Asia.html

Source: E-Drug   Author: Jing Yuanyuan