Category Archives: CAR-T

Roche and SQZ expand cell therapy deal to more than $1.3bn

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US biotech SQZ Biotechnologies has expanded a collaboration with Roche to develop cancer therapies based on antigen presenting cells, which may be able to target solid tumours and which are cheaper to make than the recently approved CAR-T drugs.

The deal announced late yesterday expands a collaboration that began in 2015 to a deal worth more than $1.375 billion if all development targets are met.

SQZ’s technology is based around antigen presenting cells (APCs), which occur naturally in the body and present antigen on their surface to stimulate a T-cell response against that particular antigen.

SQZ is able to genetically engineer APCs with tumour antigens, that when injected into the body can produce powerful responses from CD8 T-cells – also known as killer T-cells.

The hope is that these killer T-cells will produce a strong response against any tumour target of interest, across a wide range of cancers.

Roche already has a cancer immunotherapy on the market – its Tecentriq (atezolizumab) is already approved in certain kinds of bladder and lung cancer.

But unlike Novartis and Gilead it does not have cell therapy approved yet and is looking to develop cell therapies that could be used in solid tumours, instead of blood cancer like its rivals’ CAR-T therapies.

Under the collaboration, SQZ may receive up to $125 million in upfront payment and near-term milestones.

SQZ could earn up to $250 million in clinical, regulatory and sales milestones per product that emerges from the collaboration.

The Massachusetts-based biotech may receive development milestone payments of over $1 billion. Within the collaboration, SQZ and Roche could share commercial rights for certain approved products.

Howard Bernstein, chief scientific officer of SQZ, said: “This collaboration allows for a SQZ APC product engine that could potentially generate products with more potent immunologic responses through a simplified, more efficient manufacturing process.”

Chimeric antigen receptor T-cell (CAR-T) drugs are potentially curative in the patients that respond – but are very expensive to make as they involve harvesting a patient’s T-cells, genetically modifying them in a lab, and then re-injecting them to fight cancer.

SOURCE: www.pharmaphorum.com/news

Ahead of the curve

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Pharma often criticises the NHS for failing to adopt the latest therapies, arguing that NICE’s technology appraisals can drag on and that hospitals often fail to provide the recommended therapies anyway.

However in the case of CAR-T therapies, it seems that it has responded to the criticism – at least in part, anyway.

Chimeric antigen receptor T-cell (CAR-T) therapies from Novartis and Gilead were approved by the European regulators in August – and the NHS was quick to strike deals to make them available to patients in England.

At the end of August, the European Commission approved Kymriah in children and young adults aged up to 25 with refractory acute lymphoblastic leukaemia (ALL), in relapse post transplant or in second or later relapse.

Within days the NHS had announced a deal with Novartis giving paediatric patients access to its CAR-T, Kymriah (tisagenlecleucel).

And although Gilead’s CAR-T, approved for adults with relapsed or refractory large cell lymphoma, was initially rejected by NICE, the manufacturer has managed to strike a deal with the NHS to allow patients access with reimbursement from the Cancer Drugs Fund.

Novartis’ CAR-T has been rejected by NICE in its adult indication, but this could well change if the Swiss pharma strikes a similar deal.

Horizon scanning

What stands out about the CAR-T story is that NHS officials saw that these therapies were heading to market quickly, after regulators allowed them to be approved on the basis of smaller trials, something that was possible because the therapies can be very effective in the patients that respond.

NHS chief executive Simon Stevens publicly said that getting CAR-Ts to patients is a priority – even though they are costly to manufacture, and patients need intensive monitoring to ensure they do not develop the fearsome side-effects associated with the therapy.

At Kisaco Research’s Combined CAR-T conference in Berlin earlier this year, experts revealed how the NHS had already begun to develop specialist centres capable of providing the therapies.

And a mock assessment by cost-effectiveness experts prior to approval had already indicated that the therapies could be good use of NHS resources, despite their high costs.

The NHS has built on this and is working on further CAR-T centres at hospitals across the country.

Speaking after the latest deal with Gilead, Stevens said: “CAR T-cell therapy is one of the most promising new treatments in a generation for lymphoma and leukaemia, and NHS patients will now be among the first in the world to benefit.”

Dr Alasdair Rankin, director of research and patient experience at the blood cancer charity Bloodwise, said: “CAR-T therapies have shown huge promise in treating patients with lymphoma who have no other chance of cure. It’s admirable that the NHS and the pharmaceutical company have worked hard to make this pioneering treatment available so quickly, giving hope to current patients and their families.”

But as Bloodwise’s Rankin points out, getting reimbursement in place is just a first step – the experience in the US shows that despite all the prep work by hospitals, getting the therapies to patients is still a logistical challenge.

The manufacturing process involves taking a patient’s own T-cells, sending them to a lab where they are genetically modifies, before sending them back to the patient where they are re-injected to fight the cancer.

Financial results from Novartis and Gilead, and anecdotal evidence, suggests that only a few patients have received the therapies outside of clinical trials as hospitals struggled through a backlog of eligible patients.

Rankin said in a statement: “The next big challenge for the NHS will be to deliver this new and complex treatment on a scale that ensures access for the hundreds of patients with these lymphomas who could benefit from CAR-T therapy each year.

Off-the shelf

The challenges posed by CAR-T therapies are immense – but the good news is that scientists are working on ‘off-the-shelf’ drugs that are made from banks of cells and can be administered to many different patients.

These therapies promise to have similar efficacy to CAR-T, but at a fraction of the price and without the costly and time consuming electrophoresis process used to harvest the T-cells.

At the CAR-T Congress earlier this year, researchers at MD Anderson Cancer Center at the University of Texas estimated that ‘off-the-shelf’ therapies derived from natural killer (NK) cells could be made available at 1% of the cost of CAR-T cells.

CAR-NK cells would be derived from cord blood, allowing them to be stored in banks and used on several patients, vastly reducing manufacturing expenses.

There is also the possibility that future cell therapies could target solid tumours, something that is not possible with Kymriah or Yescarta.

These therapies are not able to target the antigens present on solid tumours, and the CAR-T cells are not tough enough to infiltrate tumours.

Kymriah and Yescarta are just the start – whether the NHS is agile enough to keep pace with cell therapies for cancer and other diseases as they are developed remains to be seen.

Bloodwise’s Ranking concluded: “It is likely that we are only beginning to see the benefits that CAR-T therapy can bring. Treatments will continue to improve and become more effective over the coming decade and will benefit patients with other types of cancer.”

SOURCE: www.pharmaphorum.com/views-analysis-oncology

Novartis’ CAR T therapy Kymriah to become available on the NHS

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Novartis’ Kymriah is set to become the first CAR T therapy to become available on the NHS after it was revealed that the cancer treatment will be offered to children and young adults up to the age of 25 years old with B-cell acute lymphoblastic leukaemia (ALL) that is refractory, in relapse post-transplant or in second or later relapse.

While both Gilead and Novartis’ CAR T therapy were awarded marketing authorisation in the European Union just last week, NICE were quick to reject Gilead’s CAR T therapy Yescarta on the grounds that it was too expensive.

However Novartis’ one time cancer treatment is now set to become available through the UK’s national healthcare system.

Mari Scheiffele, Novartis Oncology General Manager, UK & Ireland, said: “This decision to make our revolutionary CAR-T therapy, Kymriah (tisagenlecleucel) available so soon after being licensed is the result of our close collaboration with NHS England and NICE, with flexibility shown by all parties to ensure young patients can access this life-saving treatment as quickly as possible.”

The custom made treatment, which uses an individual’s own immune cells to combat cancer, has the potential to extend survival and significantly improve quality of life for children and young adults whose prognosis is poor.

However the cancer therapy comes with a high price tag, costing $475,000 in the United States. Meanwhile the list price for Gilead’s alternative Yescarta is just $373,000 in the US. Nevertheless the price that has been negotiated between Novartis and NICE will be kept confidential.

SOURCE: www.pharmafile.com/news/518554

NICE rejects Gilead’s CAR-T, immediately after EU approval

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Novartis and Gilead’s CAR-T therapies have been approved in Europe – and the UK’s NICE immediately slapped down the latter, saying it is too expensive for regular NHS use in England and Wales.

Novartis’ CAR-T, Kymriah (tisagenlecleucel) has not yet been reviewed by NICE’s committees, as the cost-effectiveness body received the manufacturer’s dossier much later.

But if NICE’s decision on Gilead’s CAR-T (chimeric antigen receptor T-cell) therapy, Yescarta (axicabtagene ciloleucel) is anything to go by, Novartis may also have difficulties securing market access on England’s NHS.

In its document summarising its assessment of Gilead’s drug, NICE noted the good response rates, overall survival and progression-free survival data from clinical trials of Yescarta in diffuse large B-cell lymphoma and primary mediastinal B-cell lymphoma in people who have had two or more systemic therapies.

But NICE said there was a lack of comparator data with standard care of salvage chemotherapy, so it was unable to quantify the exact size of the drug’s benefit.

Gilead has kept the list price a secret, and NICE merely said that the cost per Quality Adjusted Life Year was in excess of £50,000, its upper limit for medicines given to patients at the end of their lives.

However the medicine does not come cheaply – in the US Gilead set a list price of $373,000, for the therapy, a single shot of a patient’s own T-cells, harvested and genetically modified to destroy certain blood cancer.

NICE’s independent assessment committee also considered whether Yescarta could be reimbursed on an interim basis by the Cancer Drugs Fund until new clinical data comes to light.

But the committee said Yescarta does not have plausible potential to be cost-effective.

Meindert Boysen, director of the centre for health technology evaluation at NICE, said: “CAR-T is an exciting innovation in very difficult to treat cancers, with a promise of cure for some patients.”

“We have been working with the companies involved, and with NHS England, with the aim of ensuring that patients in England are among the first to have access to these new treatments in Europe.”

“Although promising, there is still much more we need to know about CAR-T, and unfortunately, in this case, we are not able to recommend axicabtagene ciloleucel for use in the NHS in England at the cost per patient set by (Gilead’s subsidiary) Kite Pharma.”

However in the long term, it looks likely that CAR-T therapies will be available for NHS patients: as revealed by pharmaphorum earlier this year, the NHS has been doing extensive groundwork ahead of their approval, including setting up specialist centres.

The approved indications for Yescarta are adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) and primary mediastinal large B-cell lymphoma (PMBCL), after two or more lines of systemic therapy.

Kymriah has been approved for the treatment of paediatric and young adult patients up to 25 years of age with B-cell acute lymphoblastic leukaemia (ALL) that is refractory, in relapse post-transplant or in second or later relapse; and for the treatment of adult patients with relapsed or refractory (r/r) diffuse large B-cell lymphoma (DLBCL) after two or more lines of systemic therapy.

SOURCE: www.pharmaphorum.com/news

Veteran analyst Eric Schmidt moves over to biotech as Allogene’s new CFO

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Longtime Cowen analyst Eric Schmidt is joining Arie Belldegrun’s latest CAR-T startup, Allogene, as its chief financial officer.

The announcement comes six weeks after Schmidt confirmed that he was considering a job offer from the company, which is working on off-the-shelf CAR-T therapies.

“Eric is an enormously talented individual with a rare blend of insight into multiple facets of the industry and deep relationships within the financial community. We are very fortunate to have him join the Allogene executive team and look forward to him applying his expertise to our vision for allogeneic cell therapy,” said Allogene CEO and President, David Chang, M.D., Ph.D, in a statement.

Schmidt joined Cowen in 1998, where he served as managing director and senior biotechnology analyst. Though he’s leaving his post at Cowen, he will stay on as a senior advisor to the company.

After creating the first CAR-T for non-Hodgkin lymphoma and selling their company off to Gilead, the former Kite Pharma executives Belldegrun and Chang returned for chapter two—allogeneic, or off-the-shelf CAR-T. They launched the startup in April, with $300 million in series A capital and a suite ofe early-stage allogeneic CAR-T assets, licensed from Cellectis, by way of Pfizer.

Pfizer licensed 16 CAR-T assets from Cellectis in 2014 for $80 million up front and another $185 million per product up for grabs, making the deal potentially worth as much as $2.9 billion. A year later, Pfizer and Servier gained the rights to another CAR-T candidate, UCART19, which has now become Allogene’s lead asset, with phase 2 trials slated to start in 2019.

While Kite and Novartis earned the first approvals for CAR-T treatments in 2017, there remains much room for improvement. Their therapies, Yescarta and Kymriah, are both indicated for blood cancers, with most CAR-Ts seeing limited success in solid tumors. Moreover, CAR-T cells are made by collecting a patient’s T cells, modifying them to better target and destroy cancer and then putting them back into the patient. This makes manufacturing complex and time-consuming. An allogeneic approach uses donor cells, which can be stored and used off the shelf.

“I’ve watched and analyzed dozens of companies as they worked to bring innovative and transformative new therapies to the market,” Schmidt said. “I have greatly admired the team and investors behind Allogene and consider myself very fortunate to be in a position to help make a difference in the lives of patients who are facing cancer.”

SOURCE: www.fiercebiotech.com

Gilead signs $3bn-plus gene-editing deal with Sangamo

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Gilead Sciences has claimed another stake in the emerging cell therapy sector with a $3bn agreement to use Sangamo Biosciences gene-editing platform for new cell-based cancer therapies.

The company seems determined to stay in the forefront of the pharma industry’s push into cell therapies, with the latest deal coming shortly after it acquired CAR-T specialist Kite Pharma for $12bn and almost immediately bolted on another CAR-T tech through the takeover of Cell Design a few weeks later.

Sangamo is getting $150m upfront from Gilead in the deal, which will see Kite claim an exclusive license to use the biotech’s zinc finger nuclease (ZFN) technology to develop up to ten off-the-shelf (allogeneic) as well as autologous CAR-T therapies. It also stands to receive up to $3bn in milestones – $300m per product – as well as tiered royalties on sales.

Kite will be responsible for all development, manufacturing and commercialisation of products under the collaboration, and will be responsible for agreed upon expenses incurred by Sangamo.

Gene-editing techniques are used to modify the cells – either harvested from patients or taken from donor stocks – that are infused into cancer patients in order to mount an immunotherapeutic assault on cancers. The deal with Sangamo means rivals in the CAR-T category such as Novartis, Celgene/Juno and off-the-shelf specialist Cellectis won’t be able to use the ZFN technology in their own gene-editing toolboxes.

ZFN is a gene-editing approach that uses a DNA-cutting nuclease enzyme attached to zinc finger -binding proteins to recognize and edit specific sequences of DNA. Other techniques include CRISPR/Cas9 – used by Novartis and Juno – and Cellectis’ favoured TALENS.

However, according to CEO Sandy Macrae, Sangamo has made significant strides in improving the precision, efficiency and specificity of ZFN, which means the technique now “sets the standard on what therapeutic genome editing should be”.

He said that Kite’s “financial strength and clear determination” to bring new cellular therapies products forward makes it an ideal partner for ZFN in this setting.

Kite highlighted the potential of the technology for developing allogeneic CAR-Ts, which have been put forward as potentially a major advance over autologous therapies, as they should be much quicker and cheaper to deliver – an important consideration given the current debate over the escalating costs of cancer treatment.

“The emergence of gene editing as a tool to edit immune cells holds promise in the development of therapies with potentially improved safety, efficacy and efficiency,” commented Gilead’s CEO John Milligan.

SOURCE: www.pmlive.com/pharma_news