23 January 2019

Amgen’s Blincyto gets expanded indication for B-cell ALL in Europe

The European Commission (EC) has granted approval for the use of Amgen’s Blincyto as a monotherapy to treat adults with Philadelphia chromosome negative (Ph-) CD19 positive B-cell precursor acute lymphoblastic leukaemia (ALL).

The indication covers patients who are in first or second complete remission and have a minimal residual disease (MRD) greater than or equal to 0.1%.

Blincyto is a bispecific CD19-directed CD3 T cell engager based on Amgen’s BiTE antibody construct technology that aids the body’s immune system to attack cancer cells.

The drug is the first BiTE immunotherapy, and the company is currently developing multiple other candidates targeting hematologic and solid tumours.

Amgen Research and Development executive vice-president David Reese said: “This approval represents a paradigm shift in the management of ALL in the European Union, making Blincyto the first and only treatment with marketing authorisation to include the presence of MRD.

“We are pleased that the European Commission has seen the value Blincyto can bring to people living with ALL and are proud to continue to deliver on our commitment to the pursuit of breakthroughs that can transform the lives of cancer patients.”

The approval comes after review of results from the Phase II BLAST clinical trial performed in adults with MRD-positive B-cell precursor ALL in complete hematologic remission following three or more cycles of chemotherapy.

During the open-label, multi-centre, single-arm trial, the drug was evaluated for its efficacy, safety and tolerability.

Results showed that the drug triggered a complete MRD response, or no detectable MRD, in 78% of patients who received one treatment cycle.

Safety profile in MRD-positive patients was observed to be consistent with the known profile in relapsed or refractory B-cell precursor ALL.

Currently, Blincyto holds approvals in a total of 57 countries, including all member countries the EU and EEA, the US, Canada, Japan and Australia.

The drug secured the European authorisation for Ph- relapsed or refractory B-precursor ALL last year.

22 January 2019

Researchers find new mechanism to control spread of breast cancer

Researchers at the Fred Hutchinson Cancer Research Center in Seattle, US, have discovered how cells that have broken away from breast cancer tumours evaded chemotherapy and have pointed to a new possible therapeutic option to reduce breast cancer metastasis.

The study, which was published in Nature Cell Biology, showed that disseminated tumour cells (DTCs) were found most commonly in the bone marrow because they were stuck to blood vessels by signalling proteins called integrins.

This led to the conclusion that the relationship between the DTCs and integrins was the mechanism allowing DTCs to evade chemotherapy, rather than the DTCs lack of division, as was previously assumed.

The team collaborated with Peter Nelson’s laboratory at the centre to use RNA sequencing to prove it was the integrins, rather than another protein, that was responsible for connecting the DTCs to blood vessels.

In organanotypic cultures seeded with human breast cancer cells, the team was able to use integrin inhibitors to kill the DTCs without waking them up, which showed that cell division was not necessary to encourage chemotherapy action.

Lead author of the study Dr Cyrus Ghajar said: “It’s always been assumed that dormant cells cannot be killed by any kind of chemotherapy because they’re not dividing.

“But what we’re showing is that’s not true. They’re relying on survival signalling in their microenvironment, in this case specifically from blood vessels within the bone marrow. And if you can take away that signalling, you can sensitise them to chemotherapy.”

He continued: “Chemo on its own would kill one third of all the single cells in our culture. But when we combined integrin inhibition and chemotherapy, we killed over 90% of the single cells in our cultures.”

The researchers also used mouse models with breast cancer in the study. They found that a combination of integrin inhibitor and chemotherapy was able to reduce the number of DTCs in the bone marrow by 94% and the probability of metastatic recurrence was reduced significantly.

The next step from these findings is to create human versions of the molecule used for integrin inhibition and to test to see if it is safe in humans.

Ghajar said he believes the team’s demonstration that dormant cancer cells can be killed by chemotherapy without activating them is a significant discovery in itself.

“No matter what happens with regard to the specific molecules we’ve discovered, that concept is going to endure,” Ghajar said.

21 January 2019

UK royal college updates guidance on combined hormonal contraception

The UK Royal College of Obstetricians and Gynaecologists’ Faculty of Sexual and Reproductive Healthcare (FSRH) has updated its guidance on combined hormonal contraception to conclude there is no health benefit from taking a seven-day hormone break every 21 days.

Combined hormonal contraception includes a combined pill consisting of both oestrogen and progesterone, as well as a vaginal ring and transdermal patch.

The FSRH guidance, which is accredited by the UK’s pricing regulator the National Institute of Health and Care Excellence, also stated that patients can safely taker fewer or no breaks from contraception to avoid monthly periods and related symptoms.

It goes on to say if an interval is taken, shortening it from seven to four days could further reduce the risk of pregnancy.

FSRH vice-president for clinical quality Dr Diana Mansour said: “Pill-taking often isn’t perfect; the riskiest time to miss pills is at the beginning and the end of a pill-free interval. The guideline suggests that by taking fewer hormone-free intervals – or shortening them to four days – it is possible that women could reduce the risk of getting pregnant on combined hormonal contraception.”

The co-director of the faculty’s clinical effectiveness unit Dr Sarah Hardman said: “Combined hormonal contraception can allow women to have a regular monthly bleed, whereas bleeding can be unpredictable with some other contraceptives. It can make periods lighter and less painful too.

“If a woman wants to avoid periods on combined hormonal contraception she can run the packets together – we don’t need a regular monthly bleed to be healthy, and lots of women welcome the option of avoiding bleeding.”

In line with the NHS’s new digital focus, another update in the guidance argues online consultations are sufficient for combined hormonal contraception.

Also, the FSRH recommends that women can be safely prescribed a one-year supply of contraceptive pill after their first consultation, rather than three months.

Mansour continues: “If the combined pill is the woman’s preferred option and it is deemed safe for her, clinicians can prescribe a year’s supply at the first consultation, with recommended annual follow-up.”

21 January 2019

Novartis and University of Oxford partner on AI-based drug development

Novartis has partnered with the University of Oxford’s Big Data Institute (BDI) to boost drug development using artificial intelligence (AI) and advanced analytics.

The partners intend to focus on analysis, combination and interpretation of datasets to identify markers that allow early prediction of patient responses to therapies for inflammatory diseases, including psoriasis.

As part of the alliance, relevant clinical trial data from Novartis will be combined with data from nearly five million patients from the UK and other international partner organisations.

The prediction of patient responses to medicines is expected to be enabled through BDI’s statistical machine learning technology and data analysis, along with Novartis’s clinical specialism and trial data.

Novartis and BDI also plan to develop an AI technology and IT environment to identify patterns in data.

In addition, the partners will work on the characteristics of select diseases to gain a better insight into disease progression and commonalities between diseases.

Novartis chief medical officer and global drug development head John Tsai said: “Our work with the Big Data Institute will enable us to combine different types of data such as clinical, imaging and genomics, and use advanced analytical capabilities to change how we look at diseases and discover new insights.

“This has the potential to transform how we design and conduct our clinical development programmes of the future.”

Initially, the partners will focus on two of Novartis’s global drug development organisation programmes to further understand multiple sclerosis, dermatology and rheumatology.

Big Data Institute director Gil McVean said: “Our collaboration with Novartis will enable both organisations to transform the scale and efficiency of clinical research at an unprecedented rate through the sharing of data, technology, and advanced analytics expertise.

“The BDI enables people and projects to span traditional boundaries and scientific disciplines, and leverage technological innovation for the benefit of patients.”

The collaboration covers knowledge exchange and access to a network of scientific talent. It will also leverage the expertise of various other partners.

18 January 2019

Survey shows efficacy of BoNT-A treatment for spasticity

An international survey conducted by biopharmaceutical group Ipsen and social media platform Carenity found a significant hidden burden associated with spasticity. For 94% of those surveyed, satisfaction with life improved following treatment with botulinum toxin type A (BoNT-A) injection.

Spasticity is a condition associated with neurological diseases, such as stroke, traumatic brain injury and multiple sclerosis, and is characterised by velocity-dependent muscle hyperactivity.

The survey confirmed that spasticity has a large impact on the ability of sufferers to perform ordinary tasks, as well as sex life and self-esteem. It also affected patients’ ability to work; 22% of patients surveyed did not work and 78% had had to take time off work because of the condition.

In terms of treatments, 90% of respondents wanted long periods without symptoms and a significant improvement in their quality of life.

Ipsen’s pipeline includes two pre-clinical BoNT-A products.

The company’s executive vice-president of research and development and chief scientific officer Alexandre Lebeaut said: “Spasticity is not always the first symptom that is managed in adult or children central nervous system insult, but it has a long term and chronic profound impact on fundamental aspects of patients and caregivers’ daily lives.

“The hallmark of good patient care is providing access to effective treatments that can control symptoms, and improve quality of life.”

PM&R senior consultant and head of the department of adult neuro-rehabilitation at Centro de Medicina de Reabilitação de Alcoitão, Portugal, Jorge Jacinto said: “The Carenity survey, as well as observational studies like ULIS-III5 provide priceless patients insights to clinicians.

“It will allow us to not only consider the burden of spasticity in its entirety, but also rethink the treatment paradigm to improve patients’ and caregivers’ quality of life.”

The Ipsen-Carenity survey had 615 participants, 69% patients and 31% caregivers, across six countries in Western Europe and the US. The results were presented by Ipsen at the Toxins conference in Copenhagen, Denmark.

18 January 2019

Proteus Digital Health introduces digital medicines for cancer

In collaboration with Fairview Health Services and University of Minnesota Health in the US, Proteus Digital Health has launched digital medicines to boost outcomes for cancer patients.

The digital oncology medicines are intended to support treatment regimens and aid patients in completing oral chemotherapy cycles.

In addition, the products will offer insights into patients’ treatment progress and overall health status.

The partners developed a care model for oral digital oncology medicines.

Fairview Health has become the first organisation to prescribe digital capecitabine, a chemotherapy drug, for use with the Proteus ingestible sensor.

Currently, the digital medicine is being used to help treat patients with stage 3 and 4 colorectal cancer.

Proteus Digital Health CEO and co-founder Andrew Thompson said: “For the first time, digital oncology medicines give providers and caregivers new insights and ability to engage with more specific information in the remote care of colorectal cancer patients.

“Based on our data around the use of digital medicines in other treatment areas, we believe this will enable oncology patients to stay on their therapy longer, avoid hospital admissions, and have better response to therapy overall.”

The digital medicines programme is designed to capture, record and share information regarding the time, dose and type of oral chemotherapy medication taken by the patient.

Patients can choose to share the medication information as well as data on rest, activity and resting heart rate with their physician, pharmacist or caretaker on a secure platform developed by Proteus.

Proteus is additionally introducing a digital oral oncolytic medication registry in order to collect more real-world data from cancer patients using digital medicines.

The study will gather information from several sites, where patients will be prescribed digital capecitabine to aid their treatment.

Study findings will be used to share best practices across multiple sites, enabling enhanced data and outcome analysis.

16 January 2019

FDA announces new policies for cell and gene therapies

Despite most of the US Food and Drug Administration’s (FDA) responsibilities grinding to a halt as a result of the US Government shut down, FDA commissioner Scott Gottlieb and Centre for Biologics Evaluation and Research director Peter Marks have released a joint statement laying out the regulator’s policies regarding cell and gene therapies.

The new policies will focus on increasing the number of employees in review groups evaluating cell and gene therapy drug applications, proper use of expedited programmes and issuing new guidance.

The FDA’s regenerative medicine advanced therapy (RMAT) designation and other accelerated approval pathways are examples of expedited programmes that will be used more effectively.

The new series of guidance documents focused on active product development, including gene therapies for inherited blood disorders and issues related to creating gene therapies for neurodegenerative diseases.

The FDA’s guidance will also discuss how "a more traditional approach to drug development may be more appropriate if the gene therapy creates a genetic alteration aimed at treating the symptoms of a neurodegenerative disease, or potentially altering its course by altering the expression of a protein or enzyme believed to play a role in the advance of a disease", meaning the gene therapy does not aim to cure the disease, but treat underlying symptoms.

Another guidance will focus on how to tackle "complexities associated with manufacturing these products in a safe, reliable and cost-effective way, and in a manner that allows for the efficient use of these products in the clinic".

This is already an issue for gene therapy – Novartis, creator of CAR-T therapy Kymriah, has already experienced serious manufacturing issues related to the therapy, although the drug was only approved in 2017 in the US.

To ensure companies comply with regulations and to assist smaller companies, the FDA will also issue a guidance regarding creating more efficacious pathways for biologics licence application, including a proposed innovative trial design and pooling clinical data following a common manufacturing protocol.

The announcement is in response to a recent surge in cell and gene therapy products, which has led the regulator to predict "by 2020 we will be receiving more than 200 INDs [investigational new drugs] per year, building upon our total of more than 800 active cell-based or directly administered gene therapy INDs currently on file with the FDA. And by 2025, we predict that the FDA will be approving ten to 20 cell and gene therapy products a year based on an assessment of the current pipeline and the clinical success rates of these products".

14 January 2019

UK and Japan partner on treatments for degenerative diseases

Medical researchers in the UK and Japan are set to work together on advancing research aimed at developing treatments for chronic degenerative and incurable diseases, including diabetes and heart disease.

Under the collaboration, £10m will be allocated to a programme focused on regenerative medicine. The project will be led by the UK’s Medical Research Council (MRC) and the Agency for Medical Research and Development (AMED) in Japan.

The researchers will focus on gaining more insights into critical regenerative processes in human health and translate the findings into tools and technologies for treating patients.

It is expected that the project will yield new medicines for cancer and to repair damage caused by degenerative conditions such as motor neurone disease, multiple sclerosis and Parkinson’s disease.

In addition, businesses in the UK and Japan will partner to develop a new generation of assisted living products and services by leveraging artificial intelligence and robotics.

UK Health Secretary Matt Hancock said: “As global leaders, the UK and Japan must work closely together to tackle key emerging issues in healthcare, like the challenges of an ageing population and how we can harness the power of technology to revolutionise care.

“The UK has one of the most advanced health systems in the world and is leading the way in life sciences, genomics and artificial intelligence. Japan will be a crucial partner in the future to develop the next generation of treatments as part of our long-term plan for the NHS.”

The alliance will focus on increasing the life expectancy of older people, in line with the NHS's long-term plan and the modern Industrial Strategy’s Ageing Society Grand Challenge.

This is intended to be achieved by using technology to detect and prevent diseases earlier.

UK Business Secretary Greg Clark added: “This government wants to give older people at least five extra healthy independent years of life by 2035. Our modern Industrial Strategy and its Ageing Society Grand Challenge aims to put the UK at the forefront of new technologies.”

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