CAR-T cell therapy raising hopes for cancer patients, medical tourism

CAR-T therapy is seen to be on the verge of a breakthrough, raising hopes for both cancer patients as well as medical tourism. But can it become the first line of treatment?

At least 50 patients go for CAR-T treatment to China, which has more than 200 outfits working in this area, say industry insiders. In comparison, India has three players, and only one of them — ImmunoACT — has a CAR-T product available commercially.

But things could change.

Rahul Purwar, founder and chairman of ImmunoACT, says not many would have gone to China for treatment since the IIT Bombay spin-off, backed by Hyderabad-based Laurus Labs, started commercially offering CAR-T therapy (NexCAR19) in India last November.

“We are offering the treatment at $50,000 and their cost is around $200,000. So, India obviously has a major edge here,” he says.

In the US, this costs $800,000-$900,000 per patient, including pre- and post-infusion care.

The immune system is the body’s natural defence against infections and old or abnormal cells, including those that make up cancer. In CAR-T treatment, chimeric antigen receptor T cells (CAR-T) are genetically engineered to produce an artificial T cell receptor for use in immunotherapy.

Traditionally, CAR-T is delivered through the autologous route, which involves extracting the patient’s blood, genetically re-engineering the cells, and infusing it back into the patient. The process takes three weeks or so – vein to vein.

ImmunoACT’s CAR-T product was approved by the Indian drug regulator last October for B-cell malignancies.

“If any country can bring the cost of this therapy down, it is India, as we have talented manpower,” says Esha Kaul, Director, Haemato-Oncology, Bone Marrow Transplant, Max Super Speciality Hospital, Vaishali, on the outskirts of Delhi.

Purwar says around 2,500 patients are in the queue for receiving CAR-T treatment at ImmunoACT, which is increasing its capacity. In 2024-25, it will be able to process 300-500 patients, and by March 2025 it would have a capacity to process 2,000 patients a year.

Next frontier           

The next frontier for CAR-T cell therapy for cancer is having allogeneic, or off-the-shelf, therapies for patients, bringing down the cost as well as the time to administer.

Costs can potentially come down by 75 per cent, if this therapy is made off-the-shelf. In the off-the-shelf route, a single donor’s cells are modified, preserved in minus 180 degrees, and can be infused in many patients.

Autologous versus allogeneic is a million-dollar question in CAR-T cell therapy, but the verdict seems to be unanimous – it is indeed the future of CAR-T cell therapy.

“Several people are working on this, and sooner or later a breakthrough is ought to happen,” Purwar says.

Aurigene Oncology Ltd, a Dr Reddy’s Laboratories subsidiary, is working on developing CAR-T through the allogenic route. It is also working on an autologous product at the same time.

“Many people are working on allogeneic CAR-T, but no one has yet reached the finish-line. We believe someone will crack it and that will surely disrupt this market. We do believe it (allogeneic) is the future and we are already working on it,” Murali Ramachandra, CEO of Aurigene Oncology, tells Business Standard.

DRL’s autologous CAR-T product is now in clinical trials, which are expected to take a year or so. Ramachandra says almost every day an oncologist calls to join the trials.

Immuneel Therapeutics, backed by Biocon’s Kiran Mazumdar Shaw, US-based oncologist Siddhartha Mukherjee, and 5AM Ventures’ co-founder Kush Parmar, is getting ready to bring its product to the Indian market in the next few months.

“We have finished our CD19 CAR-T (Var-cel), Indian trial (IMAGINE) for B-cell malignancies in children and adults and that has demonstrated very good outcomes — more than 83 per cent overall response rates, according to international reporting standards,” says Arun Anand, Director and Chief Operating Officer, Immuneel Therapeutics.

Twenty-four patients were treated successfully in the trial and Immuneel’s six-month survival after infusion in the trial was 92 per cent. “The regulator has granted us approval and in the next few months we hope to reach the Indian market with our product,” says Anand.

Doctors are waiting for an under-15-years age group approval.

Kaul of Max says that while both ImmunoACT and Immuneel have done trials on children, the regulator is yet to approve it for paediatric use. “Once these companies are able to submit more mature data, maybe the approval will come through,” she says, adding that CAR-T responses are often better in children.

Rahul Bhargava, Principal Director and Chief BMT, Fortis Memorial Research Institute, Gurugram, says 60 per cent patients get better with conventional chemotherapy and the current line of therapy, but 40 per cent patients with diffused large B cell lymphoma, acute lymphoblastic leukemia do not get better. “Out of these 40 per cent people, around 60 per cent patients can get better or disease-free by using CAR-T cell therapy.”

At present, CAR-T is directed towards blood cancer, but companies are working towards developing treatments for solid tumours as well. For solid cancers, now surgery helps if the tumour has not metastasized (or spread to other organs), or else one goes for a combination of chemotherapy, radiation therapy, and oral drugs.

However, clinicians do not think CAR-T will become the first line of treatment for cancers.

Supply chain

Developers of CAR-T therapy are speaking with insurance companies to substantially increase the patient coverage. But there is another way to bring the costs down — by localising the supply chain.

A virus vector called lentivirus, or a protein called IL-2, are often in short supply in the global supply chain with the rising demand for CAR-T cell therapy worldwide. It is estimated that more than 1,200 CAR-T projects are ongoing across the world. The horizons are broadened beyond cancer; for example, Reliance Life Sciences has tied up with IIT Kanpur for using CAR-T for genetic eye disorders.

“Most of the raw materials needed are imported now, but recently a few Indian companies have shown promise. They are meeting all quality standards and have also started supplying overseas. Let’s say even if 40-50 percent of the supply chain gets localized, costs can come down significantly,” says Ramachandra of Aurigene.

Anand Immuneel highlights that these are expensive technologies and one has to emphasise on ensuring quality standards: “So, the best therapy at global standards at the right value should be our focus – and not achieving lower costs alone.”

Moreover, he says, allogeneic therapy is still early in its journey. “Autologous therapies given over a short course of seven to 10 days have some advantages versus allogeneic, particularly in lack of graft versus host disease and ability to create better memory. In our experience, within weeks we see the tumour regress,” he adds.

Does CAR-T free patients from cancer in the long run?

Experts say physicians should be careful when saying “free of cancer”. “Patients are typically in remission for a few years before they can be declared free of cancer. “We can always say at this point that we are not detecting cancer cells,” Anand says.

Kaul adds: “In the lifetime of a leukaemia or lymphoma patient, two years is a major timeline. As one crosses that benchmark, the chances of a relapse go down, and after crossing the five-year benchmark of being disease-free the chances of relapse are really down.”

CAR-T, she says, is not going to suddenly change everything about cancer therapy; it is one more tool.

HOW DOES IT WORK

--- Chimeric antigen receptor T cells, or CAR-T cells, are cells genetically engineered to produce an artificial T cell receptor for use in immunotherapy

--- Traditionally, CAR-T is delivered through the autologous route, extracting the patient’s blood, genetically re-engineering the cells, and infusing it back into the patient

--- This process takes three weeks or so – vein to vein

--- Allogeneic CAR-T is off the shelf: Single donor’s cells are modified and can be infused in many patients as an off-the-shelf product

--- These are preserved in minus 180 degrees and can be given to multiple patients

--- Cost of CAR-T can come down by 75% if a breakthrough happens in allogeneic delivery route

--- At present, ImmunoACT offers CAR-T therapy for blood cancers at Rs 40 lakh ($48,000) per patient 

--- In the US, the costs are much higher: $800,000-$900,000 per patient, including pre- and post-infusion care