World CML Day 2014

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Early next year it’ll be 7 years since I was diagnosed with Chronic Myeloid Leukaemia. I was 32.

Today is World CML Day. The story goes that, for no reason, two of my chromosomes had broken, swapped over and created a new, naughty, one called the Philadelphia Chromosome. This sent rubbish message to my body and could have easily killed me . My white blood count was 192 on diagnosis. It should have been 7.

The (nearly) 7 intervening years have been life changing. I grew up a lot. Got married. Had a son. Fund-raised. Lobbied government. Met great people. Got better. And became a better person.

For me and a small amount of people it’s CML day every day. There are only 650 of us newly diagnosed in the UK every year. But the breakthroughs being made in the CML world have implications on cancer treatment everywhere.

I’m treated daily with two small white tablet called dasatinib. They’ve put me back together. Two small white tablets are treating my cancer. All being well I should have normal life expectancy. My hopes and dreams, outside of Luca playing for Norwich one day, are that all cancers can be treated and cured with two small white tablets. Imagine that. That’s why I keep working, volunteering and supporting, we’ve achieved so much but there is still a long way to go.

Thanks to everyone who has helped me on my journey. I’ll finish with three photo, possibly the three biggest moments in my life – all three happened after diagnosis. Have a great day everyone. K.

Wedding Day

Wedding Day

Luca was born

Luca was born

Major molecular response to CML

Major molecular response to CML

 

 

 

 

 

 

 

 

 

 

 

#‎worldcmlday‬ ‪#‎leukemia‬

Imatinib – the dawn of targeted treatments

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An excellent piece from the Cancer Research UK Science Blog:

Thirty years ago, we published research that was a key early step in the journey towards the first genetically tailored cancer drug, imatinib (also known as Glivec, or Gleevec in the United States). This drug changed the landscape, not just for those for whom it was designed – people with chronic myeloid leukaemia – but for cancer treatment as a whole.

Imatinib is unlike the conventional chemotherapy drugs that came before it. Such ‘cytotoxic’ chemo indiscriminately kills rapidly dividing cells. These include the intended target – cancer cells – but also some healthy cells like those lining the gut and mouth and hair follicle cells. Imatinib on the other hand, is specific to a molecule produced by certain cancer cells.

Imatinib featured on the front cover of Time magazine and was hailed as a “magic bullet”. It was indeed a revolution of its time – after it was approved in 2001, bed-ridden patients who’d been given just months to live were up on their feet and re-energised, thanks to their cancer being eradicated by imatinib. The story of imatinib – outlined in more detail below – is proof that if you understand the precise abnormality that is driving the cancer, there is hope for a cure. And we are proud that our early laboratory work provided a crucial stepping stone on the road to its development.

Early work
In the early 1980s, in the lab of our then Director General Sir Walter Bodmer, Cancer Research UK scientists were hard at work examining the DNA in cells. Imatinib was yet to be dreamt up, but these scientists were carrying out crucial early lab research that would increase our understanding of the genetic causes of chronic myeloid leukaemia and lay the foundations for this remarkable drug. Nigel Spurr, Peter Goodfellow, Ellen Solomon and Walter Bodmer from the charity were working with colleagues from the National Cancer Institute in America and Galton Laboratories. They discovered that the ABL cancer gene was located on chromosome 9.

On the surface, this may not be the most exciting-sounding finding. But at the time, it was like finding a needle in the proverbial haystack – it was already known that nearly all (95 per cent) people with chronic myeloid leukaemia had a major fault in this chromosome. In these people, part of chromosome 9 breaks off and sticks to chromosome 22, forming what is known as the Philadelphia chromosome – a major discovery made a decade earlier by Janet Rowley at the University of Chicago. Our scientists’ work opened up the question – was the newly located ABL cancer gene involved in this crucial disease-causing rearrangement?

A few months later, Cancer Research UK-funded scientist Nigel Spurr was part of the Dutch and American collaboration that answered the question. They demonstrated that this was indeed the case. The ABL cancer gene was definitely involved – it broke off from chromosome 9 and joined with part of chromosome 22.

A few years later, in 1985, the gene to which ABL joins on chromosome 22 was identified as BCR. And after further research, it became clear that it was the ABL-BCR ‘fusion gene’ that was fuelling the cancer – by making the cell produce a molecule (called a tyrosine kinase) that encourages white blood cells to incessantly grow and multiply.

Finding a drug
With the crucial molecular players identified, the hunt was on to find a drug that could stop them. Biochemist Nicholas Lyndon then working for Ciba-Geigy (now Novartis) and Brian Druker who was training to be a cancer doctor at the Dana-Farber Institute in America, were inspired by the prospect. They had realised that if you could block ABL-BCR, you could potentially stop CML in its tracks.

Lyndon and his team set about screening hundreds of chemicals to come up with a drug that would block the tyrosine kinase. Together with Brian Druker, he tested some likely candidates on cells grown in the lab and hit upon one that worked – they tweaked it to develop imatinib.

Astonishing results
The drug worked in cells and mice, but would it work in patients? In the mid-1990s, Brian Druker led the team which carried out the clinical trials. The results were nothing short of astonishing. The drug worked quickly and effectively in patients for whom there had previously been no hope, and imatinib became the fastest drug to be approved in history.

Before imatinib, the only real option for CML patients had been debilitating treatment with interferon or a stem cell transplant. Now, the patients could take a tablet, once a day in the comfort of their own home, and there was no need to go to hospital for treatment. And because the drug was so targeted, the side effects were limited. As Brian Druker who led the trials sums it up, “In short, it is a simple, effective treatment that disables the cancer without disabling the patient.”

It is no surprise, then that in 2009, Lyndon, Druker and another colleague Charles Sawyers, were awarded the Lasker–DeBaker Clinical Medical Research Award for “converting a fatal cancer into a manageable condition”. And earlier this year, Druker, Lyndon and Rowley were given yet another prestigious award: the Japan Prize for their part in “the “development of a new therapeutic drug targeting cancer-specific molecules”.

What about other cancers?
Encouraged by the success imatinib had seen in treating CML patients, scientists then started to turn their attention elsewhere. Could imatinib produce a similar miracle effect in other cancers where tyrosine kinases were overproduced?

In 1998, some Japanese scientists found a possible candidate – gastrointestinal stromal tumours. These tumours develop from the cells of the connective tissues that support the organs of the digestive system – the gastrointestinal tract – and generally don’t respond well to chemotherapy or radiotherapy. They found that gastrointestinal stromal tumours may be caused by faulty KIT genes. And faulty KIT genes were already known to make the cell overproduce tyrosine kinase – which meant that imatinib could work in these patients. Soon, international trials were underway to test whether imatinib could indeed be used to treat gastrointestinal stromal tumours.

From lab to clinic
Having been involved in very early lab work twenty years earlier that had led to imatinib’s development, we were then involved at the other end of the spectrum – helping to test the drug in clinical trials for people with gastrointestinal stromal tumours. Professor Ian Judson led these early trials at the Cancer Research UK Centre for Cancer Therapeutics at the ICR, in collaboration with EORTC Soft Tissue and Bone Sarcoma Group.

It was this important work that led to imatinib being approved to treat people with advanced gastrointestinal stromal tumours. Today, a sample of a patient’s tumour needs to be tested first to see if it has a faulty KIT gene before they are prescribed imatinib.

And that’s just the beginning…
Imatinib set the stage for tailored cancer treatments. Today, there are many more targeted cancer therapies in use or in trials, several of which are underpinned by our work – erlotinib (Tarceva), gefitinib (Iressa), cetuximab (Erbitux), trastuzumab (Herceptin) and vismodegib (Erivedge), to name but a few.

Our part in the story of imatinib was small but significant, and something that we’re tremendously proud of. Nobody could have known at the time how far-reaching the consequences of our research on the ABL gene would be, but that is the way of laboratory science. We don’t always know where our research today will lead, but we do know that funding work to unravel the inner workings of cancer is crucial to find the cures of tomorrow.

Around 40 per cent of our research is on fundamental biology, and there are countless examples of biological insights in the lab that have laid the foundations for new cancer treatments. Where will discoveries made in our labs today lead to in the future? Time will tell, but there’s no doubt that more ingenious ways to beat cancer are around the corner.

by Josephine Querido

http://scienceblog.cancerresearchuk.org/2012/10/25/imatinib-the-dawn-of-targeted-treatments/

FDA approves Synribo for chronic myelogenous leukaemia

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More fantastic news regarding another drug to treat CML. More hope for those who fail on other TKIs. We must ensure our UK health system funds drugs like this as they become available. Kris

The U.S. Food and Drug Administration today approved Synribo (omacetaxine mepesuccinate) to treat adults with chronic myelogenous leukemia (CML), a blood and bone marrow disease.

An estimated 5,430 people will be diagnosed with CML in 2012, according to the National Institutes of Health. Synribo is intended to be used in patients whose cancer progressed after treatment with at least two drugs from a class called tyrosine kinase inhibitors (TKIs), also used to treat CML.

Synribo blocks certain proteins that promote the development of cancerous cells. It is injected just under the skin (subcutaneously) twice daily for 14 consecutive days over a 28-day cycle until white blood cell counts normalize (hematologic response). Synribo is then administered twice daily for seven consecutive days over a 28-day cycle as long as patients continue to clinically benefit from therapy.

“Today’s approval provides a new treatment option for patients who are resistant to or cannot tolerate other FDA-approved drugs for chronic or accelerated phases of CML,” said Richard Pazdur, M.D., director of the Office of Hematology and Oncology Products in FDA’s Center for Drug Evaluation and Research. “Synribo is the second drug approved to treat CML in the past two months.”

On Sept. 4, 2012, the FDA approved Bosulif (bosutinib) to treat patients with chronic, accelerated or blast phase Philadelphia chromosome positive CML who are resistant to or who cannot tolerate other therapies.

Synribo is approved under the FDA’s accelerated approval program, which allows the agency to approve a drug to treat a serious disease based on clinical data showing that the drug has an effect on a surrogate endpoint that is reasonably likely to predict a clinical benefit to patients. This program provides earlier patient access to promising new drugs while the company conducts additional clinical studies to confirm the drug’s clinical benefit and safe use. Synribo also received orphan-product designation by the FDA because it is intended to treat a rare disease or condition.

The effectiveness of Synribo was evaluated using a combined cohort of patients whose cancer progressed after previous treatment with two or more TKIs. All participants were treated with Synribo.

The drug’s effectiveness in chronic phase CML was demonstrated by a reduction in the percentage of cells expressing the Philadelphia chromosome genetic mutation found in most CML patients. Fourteen out of 76 patients (18.4 percent) achieved a reduction in an average time of 3.5 months. The median length of the reduction was 12.5 months.

In accelerated phase CML, Synribo’s effectiveness was determined by the number of patients who experienced a normalization of white blood cell counts or had no evidence of leukemia (major hematologic response, or MaHR). Results showed five out of 35 patients (14.3 percent) achieved MaHR in an average time of 2.3 months. The median duration of MaHR in these patients was 4.7 months.

The most common side effects reported during clinical studies include a low level of platelets in the blood (thrombocytopenia), low red blood cell count (anemia), a decrease in infection-fighting white blood cells (neutropenia) which may lead to infection and fever (febrile neutropenia), diarrhea, nausea, weakness and fatigue, injection site reaction, and a decrease in the number of lymphocytes in the blood (lymphopenia).

Synribo is marketed by Frazer, Pa.-based Teva Pharmaceuticals. Bosulif is marketed by New York City-based Pfizer.

For more information:

The FDA, an agency within the U.S. Department of Health and Human Services, protects the public health by assuring the safety, effectiveness, and security of human and veterinary drugs, vaccines and other biological products for human use, and medical devices. The agency also is responsible for the safety and security of our nation’s food supply, cosmetics, dietary supplements, products that give off electronic radiation, and for regulating tobacco products.

Source: http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm325895.htm

FDA approves Pfizer leukeamia drug – Bosutinib / Bosulif

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Whilst I desperately want to celebrate a new CML drug coming into the marketplace I find it hard when I think about the dasatinib debacle we currently find ourselves in here in the UK. If Pfizer do not offer a PAH we will find ourselves lagging even further behind in CML treatment, this being said even a PAH will not guarantee availability.

This does prove to us that developments are still being made and that we must do all we can to ensure patients get access to the drugs they need, regardless of where they live.

I’ve started off with an excellent video interview with Dr. Carlo Gambacorti-Passerini, a prominent CML researcher from the University of Milan:

In this video interview from ASH 2011, Dr. Carlo Gambacorti-Passerini, a prominent CML researcher from the University of Milan Bicocca, gives us an update on bosutinib, a newer Tyrosine Kinase Inhibitor (TKI) that he has studied in-depth.  Once approved, bosutinib may provide one more option for patients and their physicians to better treat the disease while managing side effects.

WASHINGTON | Tue Sep 4, 2012 5:33pm EDT – LINK TO ORIGINAL ARTICLE

(Reuters) – Health regulators on Tuesday approved a Pfizer Inc pill for a rare type of leukemia, another step in the company’s effort to expand its oncology business.

The medicine, called Bosulif, treats chronic myelogenous leukemia (CML), a blood and bone marrow disease that usually affects older adults. About 26,000 Americans live with the cancer, and 5,430 people in the United States expected to be diagnosed with it annually, the U.S. Food and Drug Administration said.

Most people with CML have a specific type of genetic mutation called the Philadelphia chromosome. This mutation causes bone marrow to make an enzyme that triggers the abnormal growth of white blood cells. Bosulif, known generically as bosutinib, blocks the enzyme’s signal that causes the white blood cells to grow.

“We are seeing improvements in the treatment of CML based on a better understanding of the molecular basis of the disease,” Dr. Richard Pazdur, head of the FDA’s cancer drugs center, said in a statement.

Pfizer’s drug is meant for people who have CML with the Philadelophia mutation who cannot tolerate other medicines, such as Novartis AG’s Gleevec, or whose cancer has stopped responding to the older treatments.

The FDA gave Bosulif orphan status, which means it treats a condition or disease that affects fewer than 200,000 people in the United States. The designation comes with a seven-year period of marketing exclusivity.

The medicine is expected to reach peak global sales of $341 million in 2016, according to the average forecast of analysts polled by Thomson Reuters.

Bosulif is the second Pfizer cancer drug to get the FDA’s nod this year, after its kidney cancer drug Inlyta. Investors are looking for signs of the company’s research productivity, to help replace lost revenue from its cholesterol fighter Lipitor. The world’s top-selling drug began facing generic competition last year.

Shares of Pfizer were largely flat at $23.85 in after-market trading on Tuesday.

(Reporting by Anna Yukhananov, additional reporting by Bangalore equities newsroom; Editing by Leslie Gevirtz)

6 year follow up data on dasatinib

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Another study showing positive results for patients on dasatinib after 6 years who were resistant or intolerant to Glivec (imatinib). Yet more evidence showing that we need dasatinib to offer patients a complete range of treatment.

The original press release can be found here.

PARIS, June 15, 2012 /PRNewswire/

Results Presented at 17th Congress of the European Hematology Association

Bristol-Myers Squibb Company (NYSE:BMY) and Otsuka Pharmaceutical Europe Ltd., today announced six-year follow-up results from a Phase 3 randomised, open-label, dose-optimisation study of SPRYCEL® (dasatinib) in Philadelphia chromosome-positive (Ph+) chronic-phase chronic myeloid leukaemia (CP-CML) adult patients resistant or intolerant to Glivec® (imatinib).

Long-term survival data

The six-year data shows progression-free survival of 49.3% and an overall survival of 71% for patients randomised to dasatinib 100 mg once daily (n=167), with 6% of patients (n=10) progressing to accelerated or blast phase on study at six years of follow-up.[1]

Safety and tolerability data from patients randomized to the 100 mg arm during the six-year follow up are consistent with the previously reported safety profile of dasatinib 100 mg once daily. In this 100 mg QD arm, the most common grade 3/4 adverse events (AEs) were (cumulative 6 year occurrence): neutropenia (36%), thrombocytopaenia (24%), and anaemia (13%).[1] The cumulative incidence rates of the most common non-haematological AEs of Grade 3/4 at six years of follow-up were: diarrhoea (4.3%), fatigue (4.3%), infections (6.1%) and pleural effusion (5.3%).[2]

This is the longest reported follow-up of 2nd generation Tyrosine Kinase Inhibitors for patients resistant or intolerant to imatinib.

Safety and Tolerability at Six Years

Safety and tolerability data from the six-year study are consistent with the previously reported safety profile of dasatinib 100 mg once daily. For full information on SPRYCEL (dasatinib) please refer to SmPC at http://www.ema.europa.eu/.

These data were presented today at the 17th Congress of the European Hematology Association in Amsterdam. (Poster 0199).

About Study CA180-034

Study CA180-034 was designed to assess the efficacy and safety of dasatinib following intolerance or resistance to imatinib. The trial enrolled 670 CP-CML patients with resistance (n=497) or intolerance (n=173) to imatinibwho were randomised to one of four treatment arms: 100 mg once daily (n=167), 50 mg twice daily (n=168), 140 mg once daily (n=167) and 70 mg twice daily (n=168). In this pre-treated population, the median time from onset of CML to randomisation in patients on the 100 mg once daily arm was 55 months and 46% of these patients had more than three years of prior imatinib treatment. Data on the primary endpoint of the study, major cytogenetic response with a minimum follow up of 6 months in imatinib-resistant patients, have been previously reported. Thirty-one percent of patients randomised to receive dasatinib 100 mg once daily remained on treatment at 6 years.[1]

About SPRYCEL®

Discovered and developed by Bristol-Myers Squibb, dasatinib was initially approved by the FDA and the European Commission in 2006 as a treatment for adults for all phases of Ph+ CML (chronic, accelerated, or myeloid or lymphoid blast phase) with resistance or intolerance to prior therapy including imatinib and Philadelphia chromosome positive (Ph+) acute lymphoblastic leukaemia (ALL) intolerant or resistant to prior therapy. In the U.S., dasatinib received accelerated FDA approval for this indication. Since then, dasatinib has been approved for this indication in more than 60 countries worldwide.

In 2010, dasatinib 100 mg once daily was approved by the FDA and European Commission for the treatment of adult patients with newly diagnosed Ph+ CML in chronic phase. In the U.S., dasatinib received accelerated FDA approval for this indication. The effectiveness of dasatinib is based on cytogenetic response and major molecular response rates. The first-line trial (known as DASISION) is ongoing and further data will be required to determine long-term outcome. Now, more than 50 countries have approved dasatinib for this indication.

About Chronic Myeloid Leukemia

CML is a slow-growing type of leukaemia in which the body produces an uncontrolled number of abnormal white blood cells.[3] CML accounts for 15% of all leukaemias.[4] The incidence is estimated at 1-2 cases per 100,000.[5]

CML occurs when pieces of two different chromosomes (9 and 22) break off and attach to each other. The new chromosome is called the Philadelphia-positive chromosome, which contains an abnormal gene called BCR-ABL that signals cells to make too many white blood cells. There is no known cause for the genetic change that causes CML.

About Bristol-Myers Squibb

Bristol-Myers Squibb is a global biopharmaceutical company whose mission is to discover, develop and deliver innovative medicines that help patients prevail over serious diseases.

About Otsuka Pharmaceutical Co., Ltd.

Founded in 1964, Otsuka Pharmaceutical Co., Ltd. is a global healthcare company with the corporate philosophy: ‘Otsuka-people creating new products for better health worldwide.’ Otsuka researches, develops, manufactures and markets innovative and original products, with a focus on pharmaceutical products for the treatment of diseases and consumer products for the maintenance of everyday health.

Otsuka Pharmaceutical Co., Ltd. is a wholly owned subsidiary of Otsuka Holdings Co., Ltd., the holding company for the Otsuka Group. The Otsuka Group has business operations in 23 countries and regions around the world.

Visit Otsuka Pharmaceutical Co., Ltd. at http://www.otsuka.co.jp/en.

References: 1. Rea, D., et al. Six-year follow-up of patients with imatinib-resistant or imatinib-intolerant chronic-phase chronic myeloid leukemia (CP-CML) receiving dasatinib. To be presented at: 17th Congress of the European Hematology Association (EHA); June 14-17, 2012; Amsterdam, The Netherlands. 2. Shah, N., et al. Six-year follow-up of patients with imatinib-resistant or -intolerant chronic-phase chronic myeloid leukemia (CML-CP) receiving dasatinib. Oral Presentation at: 2012 American Society of Clinical Oncology Annual Meeting. 3.Macmillan Cancer Support. Leukaemia Overview.   Available at: http://www.macmillan.org.uk/Cancerinformation/Cancertypes/Leukaemia/Leukaemiaoverview.aspx. Last accessed April 2012. 4. National Comprehensive Cancer Network (NCCN). Chronic Myelogenous Leukemia – Clinical Practice Guidelines in Oncology – v.1.2007. 5. Baccarani, M. and Dreyling, M. Annals of Oncology. 2010;21:165-167.

UK job codes: 729UK12NP019 / OPUK/0612/SPC/2016, date of preparation June 2012

SOURCE  Bristol-Myers Squibb & Otsuka Pharmaceutical Europe Ltd.