News Type: Research

2021 Summer Studentship recipient Ee Jin Goh is originally from Singapore and she studies medicine at The University of Auckland.

What is the LBC Summer Studentship?
It’s a grant for students involved in current haematology research. I applied for it after I heard about the KIWI Trial.

What is the ‘KIWI Trial’?
It’s a study to analyse the effectiveness of a chemotherapy drug called Kryprolis (Carfilzomib) for newly diagnosed and transplant-eligible multiple myeloma patients.

What was your role?
I helped make it easier to accurately analyse our results by cleaning up the raw data collected, and keying it into a system that tracks patients.

Do you think this study might influence future funding of Kryprolis in New Zealand?
I do, it’s very promising as we know it induces remission early in patients. I’m interested to see the Trial with DNA PCR results, as that one may solidify what comes out of this report.

What did you get out of the grant?
I was really grateful for this opportunity. Not only did it add to my skillset as a future clinician, but having that behind-the-scenes picture of what haematology looks like and seeing real results translated into patient medicine, was pretty cool.

Current research from the Leukaemia & Blood Cancer Research Unit (LBCRU) at The University of Auckland has focused on increasing understanding of leukaemia genomics and how this information affects patient care and outcomes.

The research shows that most mutations which are relevant for blood cancer can be found in about 78 genes. Up to two years ago, only 3 genes were routinely analysed for mutation in blood cancer patients at Auckland City Hospital, giving limited insight into what was going on for each patient. This can have important consequences for the clinical course and the best treatment options for an individual patient.

Supported by Leukaemia & Blood Cancer New Zealand, the LBCRU has developed a comprehensive test that looks for mutations in all 78 genes using a “Next Generation Sequencing” platform. Over 300 patient samples have been tested including 101 with AML using an “Auckland Myeloid Gene Panel”, which showed that no two AMLs are alike as no patients with identical patterns of mutations had been encountered.

This new diagnostic test has far-reaching results. Knowing which mutations are present means that the disease can be diagnosed correctly according to World Health Organisation criteria. It means better targeted treatment with specific drugs.

A more accurate prognosis allows predictions for the severity of the disease and likelihood of success with standard treatment, or whether more intensive therapies like bone marrow transplants are required.

Unexpectedly, in some case, mutations are found not only in the cancer cells but in all cells of the patients suggesting an inherited predisposition to blood cancer. This is an important discovery as familial mutations have implications not only for the patient but for other family members as well.

LBC’s Medical Director, Professor Peter Browett is Head of the Department of Molecular Medicine & Pathology at The University of Auckland as well as LBCRU’s co-director. He describes the results of the gene panel testing for physicians as “bringing light into a previously dark room and enables them to make more informed decisions about patient management”.

A new partnership to scale up ground-breaking CAR T-cell cancer therapy in New Zealand has been announced today at the Malaghan Institute of Medical Research, with the arrival of state-of-the-art automated cell therapy manufacturing technology.

BioOra, a new company formed between the Malaghan Institute and Bridgewest Ventures NZ as part of Callaghan Innovation’s Technology Incubator Programme, will automate the manufacture of this revolutionary immunotherapy with a vision of delivering it at a fraction of current costs.

Malaghan Institute General Manager Mike Zablocki says the partnership is a major milestone in the Institute’s long term plan to help make CAR T-cell therapy a standard of cancer care in New Zealand.

“Bridgewest has extensive commercial pharmaceutical and biological manufacturing experience. It has the depth of capital to invest in the technology and infrastructure needed to scale up the CAR T-cell manufacturing processes that the Malaghan Institute has developed.”

John Robson, General Manager New Zealand of Bridgewest Ventures and Director of BioOra says the automation of CAR T-cell therapy will fundamentally transform how this therapy is delivered.

“Global research is focused on extending CAR T-cell therapy to solid cancers, and automation will allow us to bring more innovative therapies to New Zealand. Our goal is to make New Zealand a leading provider of CAR T-cell treatments by attracting developers of best-in-class therapies to access cost-effective manufacturing at BioOra for CAR T-cell clinical trials or future standard of care therapies.”

CAR T-cell therapy works by redirecting a patient’s own immune cells (T-cells) in the laboratory, to directly identify and kill cancer cells when returned to the patient. The Malaghan Institute is conducting a Phase I safety trial of a novel CAR T-cell construct for relapsed and refractory B-cell non-Hodgkin lymphoma, and plans to validate a new automated manufacturing process later this year.

Malaghan Institute Clinical Director Dr Robert Weinkove says an automated, closed-system method of manufacturing CAR T-cells, using the LONZA Cocoon® technology, will enable the Malaghan Institute to shorten manufacturing times and increase the number of trial participants. BioOra will provide contract manufacturing services to the Institute for future CAR T-cell clinical trials.

“We are planning a series of CAR T-cell manufacturing and clinical improvements – including automated manufacture – to improve patient experience and widen availability.”

Two LONZA Cocoon® platforms will be installed at the Malaghan Institute, one for research and development funded by donors, and one for manufacturing scale-up, owned by BioOra.

Dr Weinkove says philanthropic and government funding – including through MBIE’s Partnership Scheme – has been critical to the programme. This commercial investment reflects interest in the Institute’s current CAR T-cell therapy for lymphoma, developed in partnership with Wellington Zhaotai Therapies, and the potential of CAR T-cell therapies for other cancers in future.

“We now have an opportunity to scale-up CAR T-cell manufacture, with the goal of improving both affordability and availability of this potentially life-saving therapy in New Zealand.”

Attachment:

• Weinkove, Philip George, Myra Ruka, Tia Huia Haira, Giulia Giunti (2021). Chimeric antigen receptor T-cells in New Zealand: challenges and opportunities. . NZMJ 17 September 2021, Vol 134 No 1542

Background

About BioOra Limited

BioOra Limited is a portfolio company of Bridgewest Ventures NZ LP, a deep tech incubator based in New Zealand. BioOra is a partnership between Bridgewest Ventures and the Malaghan Institute of Medical Research to automate the manufacturing of CAR T-cell immunotherapy and to build out the high-value manufacturing capability in New Zealand.

BioOra aims to scale-up to provide third party manufacturing attracting first-in-class therapies to New Zealand, charging significantly lower costs for CAR T-cell therapy compared to international prices to benefit New Zealanders and attract medical tourism.

Dr Neil Domigan has recently been appointed to the position of Chief Executive of BioOra Limited. Dr Domigan has held executive roles at Genesis Research and Development Corp Ltd, co-ran a government seed venture capital fund, was a Director at Cranleigh Merchant Bank and merchant banker with Mace Consultants in Asia. He is currently Commercial Manager at the Malaghan Institute and Chief Executive of Wellington Zhaotai Therapies, positions he will continue to hold.

www.bioora.com

New Zealand’s first CAR T-cell therapy clinical trial

The Malaghan Institute, in partnership with Wellington Zhaotai Therapies, is developing and trialling a ‘third generation’ Chimeric Antigen Receptor (CAR) T-cell therapy in New Zealand and undertaking parallel research focusing on improving CAR T-cell therapies and extending them to other cancers.

A Phase I safety trial – ENABLE – got underway at the end of 2019 for people with certain types of relapsed and refractory B-cell non-Hodgkin lymphoma who have exhausted other treatment options. To date, 9 patients have been treated on this trial. A trial extension is currently planned to validate a range of clinical improvements (including automated manufacturing) ahead of any phase II trial. Results from the Phase I trial will be shared when the trial is closed in the coming months.

Alongside support from a range of philanthropic sources including Freemasons New Zealand, the Thompson Family Foundation, David Downs’ Down with Cancer campaign, the trial and research has been funded through the Health Research Council’s IRO funding and MBIE’s Partnership Scheme (matched funding of $4.9M over 5 years).

www.malaghan.org.nz/cancer/car-t-cell/

Above image: CAR T-Cell trial team at the Malaghan Institute

There’s been a lot of news over the past year regarding a revolutionary new approach to fighting cancer called CAR T-cell therapy on trial at the Malaghan Institute of Medical Research.

This option is cutting edge, and takes a patient’s immune cells (the T-cells) and re-directs them in the laboratory to identify and attack cancer cells. They then return the modified T-cells to the patient to start destroying the cancer cells.

A phase 1 safety trial called ENABLE was started at the end of 2019 for people with certain types of relapsed and refractory B cell non-Hodgkin Lymphoma who have exhausted other treatment options. Dr Robert Weinkove leads it as the Institute’s Clinical Director. He is also on LBC’s Medical and Scientific Committee.

LBC has a close relationship with the Malaghan Institute. Thanks to our donors’ support, we have assisted with funding to ensure that this trial is available for patients across New Zealand. The Institute is based in Wellington, so before the commencement of the trial, LBC provided travel grants for nursing staff from Wellington Hospital to receive intensive training in Australia where some “second generation” CAR T-cell therapies are now licensed for use on certain types of leukaemia and lymphoma.

With the trial underway, your donations enable travel and accommodation support to be available for patients outside the Wellington Region. About 12 patients are anticipated for this early exploratory phase trial. The data collected will be closely analysed with the option to lead to a phase 2 trial with more thorough tests.

In the long term, these T-cells could not only attack cancer cells but provide long-term protection against relapse, similar to a vaccine. Good things take time, and it’s early days, but with your help, LBC is delighted to support the Malaghan Institute’s ground-breaking research and stride toward our Vision to Cure.

Members of the research team in the LBCRU lab

 

Blood cancers, like all other cancers, are caused by mutations in genes (the building blocks of our cells).

Studies have shown that the type and number of mutations can vary greatly from patient to patient even though their cancer cells may look almost identical under the microscope.

Identifying particular mutations in an individual’s blood cancer is critical as it dictates how the cancer behaves, and how it will respond to treatment.

A year ago, only three genes were routinely analysed for mutations in blood cancer patients in most New Zealand hospitals. This meant that doctors had very limited insight into the spectrum of mutations that might have important consequences for the clinical course of the cancer, and help identify the best treatment plan for their patients.

With the support of donations from thousands of caring Kiwis like you, scientists at Leukaemia and Blood Cancer Research Unit (LBCRU) have developed a new test, which looks for mutations in 78 genes using a “Next Generation Sequencing” platform.

More than 100 patient samples, including 70 with acute myeloid leukaemia (AML), have been tested. So far results have shown that no two patients have exactly the same mutations even though their clinical symptoms may be similar.

The research team have successfully rolled-out the Myeloid Gene Panel for Auckland patients and are working to make the test available for all New Zealanders with myeloid blood cancers. As part of the ongoing research project they are also planning to develop a gene panel for patients with lymphoid blood cancers. It is hoped that rolling out the gene panels to patients across New Zealand will enable doctors to make more informed decisions about patient treatment and ultimately lead to better outcomes for patients.

A terminally ill man who was unable to afford $540,000 for medication to extend his life has been offered the drugs for free, thanks to a little-known scheme that could help many other cancer patients. The Nelson man has a rare type of non-Hodgkin lymphoma and has been given two years to live without treatment. But he and his wife were struggling to find the money for the drug Brentuximab. Desperate for something to extend his life his wife began researching alternatives.

One option was moving to Australia, where each of the 16 rounds needed would cost A$160 ($167) after government funding, compared with about $32,374 in NZ.
Another option was sourcing the drug from Europe and bringing it home for treatment. Four trips would be needed to source enough but at a cost of $22,300 per round it would still be cheaper than buying it in New Zealand, even with additional expenses such as airfares.

There were also other costs, including $7680 to transport it to New Zealand and $17,000 for a private hospital to administer it.
While their medical insurance would have covered $300,000, the couple would have had to remortgage their home and empty out the man’s KiwiSaver to fund the rest of the drug, which is expected to extend his life up to five years.

Fortunately, the couple was told by an acquaintance overseas about a little-known scheme called Compassionate Access Programme (CAP) where patients can apply to drug companies for free treatment. They applied through the drug-maker’s Australian office and found a fortnight ago he’d been accepted. As a result the 58-year-old man, who did not want to be identified, will now begin the almost year-long treatment for free later this week. His wife said being accepted on the CAP was a miracle, while her husband felt as if he had won Lotto.
“I never dreamed it would be paid for in full – that’s way better than I ever dreamed,” she said. “It’s shocking that people don’t know this is available, but also there’s just so many people that are in the most horribly desperate situations.”

They believed there needed to be a database where specialists could find information about the CAPs available and the eligibility requirements.
Oncologists have described schemes like this as a marketing tool drug companies use to promote products that are not approved by Medsafe, the Ministry of Health’s regulatory body.
While the schemes are great for those who can’t afford drugs, they also come with some catches.
The supply of medication could stop if Medsafe approves the drug and the patient is then stuck being unable to afford ongoing treatment. They also may not be covered by ACC if anything goes wrong because the drug is not approved here.
But the couple are ready to take the risks if it means he lives longer.

Access to lifesaving drugs is a growing issue in NZ, with cancer patients increasingly relying on fundraisers and travelling overseas to buy more affordable medication.
In May eight petitions from five cancer groups were delivered to MPs urging better Pharmac funding for drugs. Hundreds rallied in support.
Breast Cancer Foundation research manager Adele Gautier said compassionate access programmes for investigational cancer drugs appeared to be shrouded in mystery and they need to be better publicised.

“Drug companies in New Zealand can’t promote unapproved medicines, so unless an oncologist or a patient is actively working to find out what’s available, they might never know about them.”
Gautier said getting a patient access to a CAP could be time-consuming for doctors who were often busy giving short-term treatments to manage symptoms.
“Given that these are usually a last resort for patient, and delays can be life-shortening, we’d like to see this process made much easier for Kiwi patients and their doctors.”
Leukaemia & Blood Cancer NZ chief executive Peter Fergusson said the foundation was seeing a reasonable number of patients getting compassionate access from NZ-based drug companies, but it was highly dependent on the disease and their eligibility for the CAP such as the disease burden and their suitability for the medication.

“It is frustrating that New Zealand often lags behind the rest of the world for the approval and funding for life-changing cancer drugs.”
A spokesperson for pharmaceutical company Pfizer said requests for compassionate access to medicines were considered case by case.
National Party health spokesman Michael Woodhouse said he knew CAPs were offered in NZ but he had very few details about them.
He said it was frustrating cancer drugs were 75 per cent cheaper in countries such as Malaysia because it appeared the list price of the drug was scaled to a country’s wealth.

A spokesperson for Health Minister David Clark said the minister was also aware some Kiwis were buying prescription medicines overseas because prices were high in NZ.
Pharmac confirmed it was considering funding Brentuximab. Medsafe compliance manager Derek Fitzgerald said it has not received an application to approve the use of Brentuximab.
Dr Graeme Jarvis of Medicines NZ said it supported the use of the schemes in the short term, but said more investment was needed by the Government to allow these medicines to become publicly funded.

Article written by Nikki Preston (NZ Herald)

• Haemochromatosis is a common genetic disorder
• If you inherit the condition and leave it untreated, it can cause serious health problems
• Visit your doctor if you are concerned you might be storing too much iron

The health implications of one of the most common genetic disorders are being brought to attention during World Haemochromatosis Week from June 3-9. Leukaemia & Blood Cancer New Zealand provides a much-needed support service to people with this disorder.

Haemochromatosis is carried by about one in seven people. The disorder is often undiagnosed because symptoms are generic and non-specific such as tiredness, muscle weakness and joint pain.
The condition is more prevalent in people of Celtic and northern European origin and causes your body to absorb too much iron from food. This excess iron overloads body tissues, damages organs and can cause premature death.

Leukaemia & Blood Cancer New Zealand spokesperson Peter Fergusson said the condition does not need to be a burden if you find out early because it is relatively easy to manage and the treatment (giving blood) provides a benefit to others.

“People of Northern European origin are more likely to inherit the condition so it is important to raise awareness of haemochromatosis to minimise the personal impacts, risk of complications and medical costs,” Peter said.

Recent research in the United Kingdom identified the compounding health implications of haemochromatosis which include increased risk of liver disease, arthritis, diabetes and chronic pain.
This University of Exeter Medical School research will be accelerated through a new £291,000 study into the effects of haemochromatosis on other diseases, such as dementia and diabetes, and exploring why some people are more affected than others.

James Barclay is of Celtic origin and he and his wife Anne are speaking out about the need for early diagnosis to reduce complications since James was diagnosed with cirrhosis and liver cancer at age 54 as a consequence of untreated haemochromatosis.

The Barclays believe we should not dismiss symptoms of tiredness, aches and pains as being caused by gout, ageing or hard work. James and Anne are now proactively managing his health while encouraging others to take a preventive approach.

“The Barclays have an important message to share. We encourage everyone to ask their doctor for a blood test to learn about their risk,” Peter said.
To find out if you might be rusting from within and need to iron out your health, check out the haemochromatosis fact sheet on the website for Leukaemia & Blood Cancer New Zealand here.

If you or someone you know has haemochromatosis and wants support, please contact Leukaemia & Blood Cancer New Zealand.

Earlier this year, the gene panel developed by the Leukaemia & Blood Cancer New Zealand Research Unit (LBCRU) for testing acute myeloid leukaemia (AML) patient samples became available to cancer clinicians in Auckland. Now all adult patients with newly diagnosed and relapsed AML have samples collected for DNA preparation and analysis using this 70-gene myeloid panel.

HK, a man aged 57, was diagnosed with AML in August 2015. Molecular studies showed that his leukaemia cells had two abnormal genes: the NPM1 mutation and the FLT3 ITD mutation. The second carries a high risk of relapse so, in addition to chemotherapy, this is usually addressed with a bone marrow transplant.

But transplants are risky. The LBCRU estimates that between 15 and 20 percent of patients are at risk of dying in the first year from complications. It also commits the patient, family and caregivers to four weeks in hospital and two months of follow up care. It’s usually a year before they resume a normal life.

As HK was in remission after the first of four treatments, instead of going straight to a transplant, his blood and bone marrow were re-tested at the LBCRU using a super-sensitive new test at three-monthly intervals. Using the NPM1 marker, which is seen in about 30 percent of AML cases, the team’s new molecular test can find one leukaemia cell in 100,000 normal cells.

Every test after treatment was negative. Clinicians say HK is probably cured. However, if the tests had turned positive, a transplant could have been arranged before a relapse without the need for further chemo or radiotherapy.

HK’s good news story will soon be that of many New Zealanders living with blood cancers thanks to this new molecular test for a common leukaemia.

Find out more about how your donations fund research