SHANGHAI – JW Biotechnology (Shanghai) Co. Ltd., a recently formed joint venture (JV) between Juno Therapeutics Inc. and Wuxi Apptec, will continue to develop CAR T treatments for Chinese patients, taking into account the learnings from the halted trials in the U.S. that resulted after three patient deaths.

"From my perspective, JW continues business as usual," James Li, CEO of JW, told BioWorld Today. "We will continue to build our internal capabilities, continue to work toward producing CAR T-cell therapy in China and look forward to getting to the clinic in Chinese patients."

Last week, JW's U.S. parent, Seattle-based Juno, faced a significant setback when the FDA halted a phase II trial for JCAR015, a CD19-targeting chimeric antigen receptor T-cell therapy that was being studied in patients with relapsed refractory B-cell acute lymphoblastic leukemia (ALL). The clinical hold was initiated when three patients died. The deaths occurred after fludarabine was added to the pre-conditioning regimen. (See BioWorld Today, July 11, 2016.)

Fludarabine, a chemotherapy drug on the WHO list of essential medicines, is considered highly effective at treating chronic lymphocytic leukemia. A purine analogue that interferes with DNA synthesis, fludarabine is used in conditioning regimens prior to allogeneic stem cell transplant because of its immunosuppressive effects.

Juno's core CAR T technology is not thought to have caused the deaths, and Juno has proposed to continue the JCAR015 trial (known as ROCKET) using only cyclophosphamide for pre-conditioning. Juno wasted no time making revisions to the protocol and resubmitting to the FDA. The agency lifted the clinical hold late Tuesday afternoon. ROCKET will continue using cyclophosphamide pre-conditioning only.

Juno said plans for other CD19-directed CAR T-cell treatments are not affected.

For JW, a new company in China's nascent immuno-oncology field, the disappointing news is the cost of exploring new areas of therapeutic treatment.

"Setbacks are very common in drug development; I am not surprised," said Li. "There is a readiness that anything could happen in the therapeutic area like this. From my side, I feel confident, same as Juno, that they will get their product development back on track."

JW has yet to announce what products it will be developing for the China market, but Li said more information will be forthcoming early next year. Meanwhile, the JV has open communication with Juno and is working on how to best strengthen its own program. JW is also working on the CD19-related target for China, Li said.

"I don't think that the setback will affect us in the long term. In the short term, we need to figure out what is the learning and how to move forward. We will take the learnings from Juno in order to have a better clinical program when we are ready to move to the clinic."

A PATH TO PATIENTS

In another incident two months ago, a Chinese university student died after receiving DC-CIK, a dubious form of immuno-oncology treatment administered at a private clinic. A national debate ensued and the government banned the use of immunotherapies for anything other than hospital IRB-approved clinical study. Paid treatments were ordered to halt. (See BioWorld Today, May 11, 2016.)

For science-driven immunotherapy companies, the negative publicity has not been considered a bane but rather taken as a boon to the industry.

Many insiders said it has pushed the authorities to take a much closer look at what regulations are needed for the industry to grow, and removing clinically unproven treatments from the market is a good first step.

But the demand for a better path forward certainly exists; China is home to the second largest number of CAR T trials in the world, after the U.S., as listed on the U.S. clinical trials registry. Many of those trials aim to follow a rigorous data-driven approach, but as of today, it is unclear how they would find a commercially viable path to patients.

Domestic companies such as Innovative Cellular Therapeutics Co. Ltd., of Shanghai, and others are hopeful that Juno's presence here will help to set the tone for a regulatory discussion that will nudge China closer to rules for commercial development of cellular immunotherapy that more closely resemble the EU or U.S. Li said he also thinks "CAR T companies should work together with the regulators in China to set a high standard so good quality CAR T products can benefit Chinese patients."

But as a foreign-invested JV, Juno has another regulatory hurdle to navigate as well. China sets out specific industries where foreign investment is encouraged as well as other industries where foreign investment is prohibited. On the prohibited list, the first entry under the science and technology category is "the development and application of human stem cells and gene diagnosis therapy technology," according to a translation by Covington & Burling LLP. Accordingly, Juno's business license states it cannot engage in stem cells or gene therapy.

But Li does not see that as an immediate problem, especially if patients' lives can be saved.

"Firstly, CAR T is not stem cell, at this point, and CAR T is not gene therapy, at this point," said Li. "It is more important as a partially foreign-owned joint venture, we import technology that becomes home-grown technology. We will find a way to serve Chinese patients, but at this point, because the regulation is unclear, we will be working with the relevant regulators to come up with a solution so our products will be the best CAR T therapy in China to serve Chinese patients."

"If there is a lifesaving drug that can demonstrate effectiveness and a good safety profile, I think the government will reconsider how it should be regulated," Li added.