Ponatinib Access: Denied

I recently sent in a Freedom of Information request to NHS England to find out how many patients in England had requested ponatinib for chronic myeloid leukaemia and who would not already be entitled to it on the NHS. Currently only patients with the T315l mutation are able to have the drug prescribed by their doctor, with other patients who want the drug having to get a clinician to make a special request (an Individual Funding Request, or IFR) to the Cancer Drugs Fund, which NHS England runs.

I was shocked by the response to my query, that of the 14 patients who requested ponatinib (from April 2013 to March 2015), just 2 of them were granted access to the drug and the other 12 were denied. It seems short-sighted of NHS England not to allow patients access to a drug which could benefit them when others have stopped working, and when the only other option is often a stem cell transplant.

With such small patient numbers NICE won’t even consider appraising ponatinib, the CDF is supposed to act as a support system for patients to access drugs for rarer cancers, but the system clearly currently isn’t working.

Patients in England are again missing out compared to their counterparts in Wales, where the drug is fully approved for all CML patients.

This excellent graphic clearly shows that in the ponatinib PACE trial, patients benefited from ponatinib after they had failed other TKIs at various stages of disease progression.

Ponatinib: Efficacy in patients failing multiple TKIs

I’ve attached a pdf poster that outlines a national study on ponatinib and reports on the efficacy in patients failing multiple TKIs.

The conclusions were:

• Ponatinib has confirmed efficacy in a group of heavily pre-treated patients with CML.
• The probability of achieving cytogenetic response (CCyR) on ponatinib is greater in younger patients, those with prior CCyR and those without early haematological toxicity, confirmed on multivariate analyses (data not shown).
• Event free survival is higher in patients who received fewer TKI prior to treatment with ponatinib.

It makes for interesting study. For reasons of transparency this has been shared with me by an organisation who are working with ARIAD (who manufacture ponatinib).

Thanks, Kris

Download the PDF poster here.

Ponatinib: Wales 1 England 0

After the bad news yesterday, where it was announced that 25 cancer drugs will be removed from the Cancer Drugs Fund (read the full story here), I come with better news. NHS Wales will be providing access to ponatinib for ALL phases of chronic myeloid leukaemia. In England ponatinib is only available on the Cancer Drugs Fund if the patient has the T315i mutation. This progressive step by NHS Wales, based on the Phase 2 PACE trial, gives patients in Wales another, much needed line of treatment against CML. I hope that authorities in England, Scotland and Northern Ireland take note of this step forward when they assess, or reassess, ponatinib for their respective countries.

Thanks, Kris
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The positive assessment from the AWMSG is the first UK Health Technology Assessment (HTA) of Iclusig

Leatherhead, UK, 9 January 2015 — The Minister for Health and Social Services in Wales has ratified the recommendation from the All Wales Medicines Strategy Group (AWMSG) to approve Iclusig® (ponatinib) as a cost-effective treatment to be used in NHS Wales for the treatment of all phases of chronic myeloid leukaemia (CML) and Philadelphia chromosome positive acute lymphoblastic leukaemia (Ph+ ALL), in accordance with Iclusig’s licensed indication.

CML is a cancer of the white blood cells that is diagnosed in approximately 7,000 patients each year in Europe. The incidence of CML in Wales is 1.4 and 0.9 per 100,000 males and females, respectively. Iclusig is a targeted cancer medicine discovered and developed at ARIAD Pharmaceuticals, Inc.

“We are delighted that the Minister has endorsed the positive AWMSG recommendation, recognising the innovative nature of Iclusig and the potential benefit it can bring to cancer patients in Wales,” said Mark Tanner, General Manager, ARIAD UK. “Our goal is to deliver innovative solutions that address gaps in care for patients who are left with few clinical treatment options. Iclusig offers a new treatment option for many of these patients.”

The approval by the AWMSG was based on results from the pivotal Phase 2 PACE (Ponatinib Ph+ ALL and CML Evaluation) trial in patients with CML or Ph+ ALL who were resistant or intolerant to prior tyrosine kinase inhibitor (TKI) therapy, or who had the T315I mutation of BCR-ABL. In Europe, Iclusig was approved in July 2013 for the treatment of adult patients with:

• Chronic phase, accelerated phase, or blast phase chronic myeloid leukaemia (CML) who are resistant to dasatinib or nilotinib; who are intolerant to dasatinib or nilotinib and for whom subsequent treatment with imatinib is not clinically appropriate; or who have the T315I mutation;
• Philadelphia chromosome positive acute lymphoblastic leukaemia (Ph+ ALL) who are resistant to dasatinib; who are intolerant to dasatinib and for whom subsequent treatment with imatinib is not clinically appropriate; or who have the T315I mutation.

“We welcome the ratification of the recommendation from the AWMSG for the treatment of CML and Ph+ ALL with Iclusig in all its licensed indications,” commented David Ryner, Chair of the Chronic Myeloid Leukaemia Support Group. “Although the number of patients qualifying for treatment will be limited, access to Iclusig represents an opportunity to make a significant difference to their lives. We would like to see the same opportunity made available to all other qualifying patients, no matter where they live in the UK.”

About Iclusig® (ponatinib)
Iclusig is a kinase inhibitor. The primary target for Iclusig is BCR-ABL, an abnormal tyrosine kinase that is expressed in chronic myeloid leukemia (CML) and Philadelphia-chromosome positive acute lymphoblastic leukemia (Ph+ ALL). Iclusig was designed using ARIAD’s computational and structure-based drug design platform specifically to inhibit the activity of BCR-ABL. Iclusig targets not only native BCR-ABL but also its isoforms that carry mutations that confer resistance to treatment, including the T315I mutation, which has been associated with resistance to other approved TKIs.

About CML and Ph+ ALL
CML is a cancer of the white blood cells that is diagnosed in approximately 7,000 patients each year in Europe.Error: Reference source not found CML is characterised by an excessive and unregulated production of white blood cells by the bone marrow due to a genetic abnormality that produces the BCR-ABL protein. After a chronic phase of production of too many white blood cells, CML typically evolves to the more aggressive phases referred to as accelerated phase and blast crisis. Ph+ ALL is a subtype of acute lymphoblastic leukaemia that carries the Ph+ chromosome that produces BCR-ABL. It has a more aggressive course than CML and is often treated with a combination of chemotherapy and tyrosine kinase inhibitors. The BCR-ABL protein is expressed in both of these diseases.

About ARIAD
ARIAD Pharmaceuticals, Inc., headquartered in Cambridge, Massachusetts and Lausanne, Switzerland, is an integrated global oncology company focused on transforming the lives of cancer patients with breakthrough medicines.  ARIAD is working on new medicines to advance the treatment of various forms of chronic and acute leukaemia, lung cancer and other difficult-to-treat cancers.  ARIAD utilises computational and structural approaches to design small-molecule drugs that overcome resistance to existing cancer medicines.  For additional information, visit http://www.ariad.com or follow ARIAD on Twitter (@ARIADPharm).

Iclusig® is a registered trademark of ARIAD Pharmaceuticals, Inc.

You can download the original release here: AWMSG approval_FINAL release_090115

TKI survey on behalf of CML Advocates Network

A request from the CML Advocates Network who I fully endorse and would ask you complete the survey. Many thanks, Kris

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Imatinib, dasatinib and nilotinib are a tyrosine kinase inhibitors (TKIs) that have been established as effective therapies in chronic myeloid leukemia. While imatinib (marketed as Gleevec/Glivec), and in some markets nilotinib (marketed as Tasigna) as well as Dasatinib (marketed as Sprycel), have been available for some years, non-original copy versions of these drugs have also been provided to CML patients in a number of countries. With the patent ending on Glivec/Gleevec from 2013 in some markets, the use of generic TKIs in CML is becoming more and more widespread.

With the CML Horizons 2013 patient conference putting a spotlight on the situation of generics and copies in CML therapy, this survey intends to understand the availability of original TKIs and other non-original TKIs for the treatment in CML in countries all across the globe. It also aims to understand how CML patient groups are addressing the issue of quality assurance when generics and copies become available.

This survey is run by the CML Advocates Network without any commercial interest and without support from any pharmaceutical company. The results of this survey will be presented to the community at the CML Horizons 2013 meeting in May.

It should take 10-15 minutes of your time to complete the 10 questions. We would like to cover as many countries as possible – your contribution is greatly appreciated and will help us a lot!

Please respond to the survey here: http://www.cmladvocates.net/tkisurvey
(and please also respond if NO generics/copies are available in your country, which is equally important to know)

Can you please respond latest by 12 April 2013?

Many thanks and best wishes,

Jan (on behalf of the CML Advocates Network)

Dasatinib Achieves Higher Response Rate Than Imatinib in CML

The headline says it all…listen up NICE, it’s very irritating to post research like this that proves patients SHOULD have access to dasatinib. I will be writing to Sir Andrew Dillon to ask for his comments on this latest research. Kris

A study comparing the second generation tyrosine kinase inhibitor (TKI) dasatinib to imatinib for patients with chronic myeloid leukemia (CML) found that dasatinib yielded better 12-month molecular response rates and complete cytogenetic remission rates than imatinib, but these results did not translate into better survival outcomes. Rates of progression-free and overall survival were similar in both arms of the trial.

“The treatment of chronic myeloid leukemia has been revolutionized by the tyrosine kinase inhibitor imatinib mesylate, which inhibits the constitutively active fusion gene BCR-ABL, found in virtually all cases of CML,” wrote authors led by Jerald P. Radich, MD, of the Fred Hutchinson Cancer Research Center in Seattle, published online before print in the journal Blood. Trials have shown, however, that a substantial proportion of CML patients are resistant or intolerant of imatinib, and there have been indications that another TKI, dasatinib could fill that gap.

In the new trial, Radich and colleagues randomized 253 patients with newly diagnosed chronic phase CML to either imatinib 400 mg once daily or dasatinib 100 mg once daily; 246 patients were included in the final analysis. Only 11 patients had died at this point in the analysis, yielding similar overall survival rates between the imatinib and dasatinib groups of 97% for both. progression-free survival was also similar; at three years, the progression-free survival rate in the imatinib group was 90%, compared with 93% in the dasatinib arm.

Response rates were better in the dasatinib-treated patients, however. A total of 84% of dasatinib patients achieved a complete cytogenetic remission vs 69% of imatinib patients. At one year, 59% of dasatinib patients achieved a molecular response defined as a 3-log reduction in BCR-ABL transcript levels; 44% of imatinib patients achieved this level of molecular response (P = .059). The median BCR-ABL mRNA reduction after 1 year of treatment was 3.3 log for the dasatinib group and 2.8 log for the imatinib patients (P = .063).

Complete hematologic response, however, was again similar, with 82% achieving a complete hematologic response in the imatinib group and 81% in the dasatinib group (P = 1.00).

Toxicity appeared to be worse with dasatinib, with 15% of patients experiencing grade 4 toxicities compared to only 2% of imatinib patients (P = .0001).

The authors wrote that these data along with other recent trials have now painted a consistent picture: second generation TKIs such as dasatinib and nilotinib have superior short-term response rates, but with no corresponding improvement in survival. This may be due to a lack of sufficient follow-up, trials with enough patients, or simply a characteristic of the disease being treated.

“Thus for newly diagnosed chronic phase CML, we now have an embarrassment of riches—a ‘standard’ frontline therapy (imatinib) with a long-term track record with regard to response and toxicity; and two more potent second generation drugs (dasatinib and nilotinib), with an improved short-term response that may translate into long-term benefits,” the authors wrote. Choosing which drug to use can therefore be difficult for clinicians, but factors including physician experience and comfort, compliance issues (once a day with dasatinib and imatinib vs twice a day for nilotinib), obvious comorbidities that might suggest one agent over another, and that patients at higher risk of progression might benefit from dasatinib or nilotinib.

By Dave Levitan | 06 September 2012

http://www.cancernetwork.com/chronic-myeloid-leukemia/content/article/10165/2100642

Dr Jorge Cortes explains latest on existing and emerging treatments

Dr. Jorge Cortes, a renowned expert on CML and Chair of the CML Section at MD Anderson Center explains the latest news on existing and emerging treatments. This includes encouraging long-term follow-up for CML patients taking second generation tyrosine kinase inhibitors (TKIs). Dr. Cortes also comments on whether patients who are doing well on the original TKI, Gleevec, should switch. He also explains the latest information on a promising treatment in trials, Ponatinib, and the hope it gives patients who become resistant to TKIs or who have the T315i mutation not treated effectively by the approved TKIs. Dr. Cortes also comments on other drugs up for FDA review, Bosutinub and Omacetaxine, and explains which patients might benefit.

From www.patientpower.info