Ponatinib (Iclusig) – GREAT NEWS!!!

I love news like this, especially when it’s been four-years in the making.

Iclusig (ponatinib) for the treatment of Chronic Myeloid Leukaemia (CML) in adult patients with chronic phase, accelerated phase, or blast phase 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.

For CML patient in England, this means we now have another safety net that is readily available for consultants to prescribe immediately. This is going to make a big difference to treatment options and the mental well-being of many patients.

Just a quick shout to all of the people who work for and are associated with Incyte (formally ARIAD) who’ve never given up on this and have worked so hard to get it to us. Congratulations and thank you.

NICE has also recommended ponatinib for treating Philadelphia-chromosome-positive acute lymphoblastic leukaemia in adults. Hit the link for more info on this: www.leukaemiacare.org.uk/news/NICE-recommends-ponatinib

The full press release follows.

Kris

 

NICE Issues Positive Final Recommendation for Iclusig (ponatinib) for Chronic Myeloid Leukaemia (CML) in England

CML patients across the UK who are resistant or intolerant to second generation tyrosine kinase inhibitor (TKI) therapies will now have equal access to Iclusig

LONDON, UK [28 April 2017] – Incyte Corporation (Nasdaq:INCY) announces that the National Institute for Health and Care Excellence (NICE) Technology Appraisal Committee (TAC) has published a positive Final Appraisal Determination (FAD) recommending Iclusig^â (ponatinib) for the treatment of Chronic Myeloid Leukaemia (CML) in adult patients with chronic phase, accelerated phase, or blast phase 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.[i]

The positive FAD from NICE brings CML patients in England in line with those in Wales and Scotland who have had full-access to Iclusig, according to its license,[ii]^,[iii] since 2015; providing patients with CML across the UK who have failed other treatments equal access to an additional and important option.

“Today’s decision is important for patients with CML who have failed other treatments, as well as for physicians in England, who will now have access to the clinical benefits of Iclusig,” commented Mark Tanner, General Manager of Incyte Bioscience UK. “Together with the CML community, we have worked very hard over the last four years to encourage NICE to reconsider their original evaluation and are delighted that NICE has acknowledged the unmet need and the value that Iclusig brings.”

CML is a rare blood cancer with around 700 new cases each year in the UK.[iv]  CML affects economically active people, with around 50 percent of UK cases in people aged under 65 years.^iv Many patients with a new diagnosis of CML have a prolonged clinical benefit from targeted therapy with tyrosine kinase inhibitors (TKIs). However, there has been a high unmet need and poor prognosis for patients whose advanced disease is resistant and intolerant to other therapies.[v] Once available treatment options are exhausted, the prognosis can be poor.^v  Despite advances in treatment, there remains a need for additional effective therapies for the management of CML.[vi] Iclusig fulfils an important need in the treatment pathway for CML patients and provides clinicians and patients with a full suite of treatment options for CML.

Professor Jane Apperley, Department of Haematology, Imperial College School of Medicine, Hammersmith Hospital, London said, “This is an exciting and long-awaited outcome, which allows physicians to manage patients in a logical and clinical-evidence based manner with the goals of improving long-term survival and providing a good quality of life.”

Iclusig was approved by the European Commission[vii] in 2013 as an orphan drug for the treatment of adults with chronic phase, accelerated phase, or blast phase 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. In Ph+ALL (Philadelphia chromosome‒positive Acute Lymphoblastic Leukaemia) patients, Iclusig is licensed for adult patients with Ph+ ALL who are resistant to dasatinib; who are intolerant to dasatinib and for whom subsequent treatment with imatinib is not clinically appropriate. Iclusig is also licensed for people with CML and PH+ALL who have T315I mutation.[viii]

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.[ix] CML is characterized 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 Iclusig^® (ponatinib) tablets

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.

In the EU, Iclusig is approved for the treatment of adult patients with chronic phase, accelerated phase or blast phase chronic myeloid leukemia (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, or the treatment of adult patients with Philadelphia-chromosome positive acute lymphoblastic leukemia (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.

Incyte has an exclusive license from ARIAD Pharmaceuticals, Inc, a wholly owned subsidiary of Takeda Pharmaceutical Company Limited, to develop and commercialize Iclusig in the European Union and 28 other countries, including Switzerland, Norway, Turkey, Israel and Russia.

About Incyte

Incyte Corporation is a U.S.-based biopharmaceutical company focused on the discovery, development and commercialization of proprietary therapeutics. For additional information on Incyte, please visit the Company’s website at www.incyte.com.

Follow @Incyte on Twitter at https://twitter.com/Incyte.

[i] NICE. 2017. Final Appraisal Determination: Ponatinib for treating chronic myeloid leukaemia and acute lymphoblastic leukaemia. Available at https://www.nice.org.uk/guidance/gid-ta10060/documents/final-appraisal-determination-document Last accessed 28 April 2017

[ii] All Wales Medicines Strategy Group. Ponatinib (Iclusig). Appraisals. Available at: http://www.awmsg.org/awmsgonline/app/appraisalinfo/1163. Last accessed 24 March 2017

[iii] Scottish Medicines Consortium. SMC Advice. Ponatinib (Iclusig). Available at: http://www.scottishmedicines.org.uk/SMC_Advice/Advice/1032_15_ponatinib_Iclusig/ponatinib_Iclusig. Last accessed April 2017.

[iv] CRUK. Chronic myeloid leukaemia (CML) incidence statistics. Available at: http://www.cancerresearchuk.org/cancer-info/cancerstats/types/leukaemia-cml/incidence/. Last accessed April 2017.

[v] Cortes JE, KimD-W, Pinilla-Ibarz J, et al. A Phase 2 Trial of Ponatinib in Philadelphia Chromosome–Positive Leukemias. N Engl J Med 2013;369: 1783-1796. Available at: http://www.nejm.org/doi/pdf/10.1056/NEJMoa1306494.

[vi] Woessner DW, Lim CS, Deininger MW. Development of an Effective Therapy for CML. Cancer J 2011;17(6):doi:10.1097/PPO.0b013e318237e5b7. Available at: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3251313/pdf/nihms-332259.pdf. Last accessed April 2017.

[vii] EMA. Iclusig EPAR summary for the public.  Available at: http://www.ema.europa.eu/ema/index.jsp?curl=pages/medicines/human/medicines/002695/human_med_001656.jsp&mid=WC0b01ac058001d124. Last accessed April 2017.

[viii] Iclusig Summary of Product Characteristics. Available at: http://www.medicines.org.uk/emc/medicine/28145. Last accessed April 2017.

[ix] Rohrbacher M, Hasford J. Epidemiology of chronic myeloid leukaemia (CML). Best Pract Res Clin Haematol. 2009 Sep;22(3):295-302. Based on current estimate of population of Europe (738,199,000 in 2010).

 

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: 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
—

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

Tom Watson MP joins our cause!

I’m still trying to get my head around today! It may just be the most amazing thing to happen to the AccessCMLDrugs campaign to date. Tom Watson who is the Member of Parliament for West Bromwich East, Deputy Chair of the Labour Party and the Labour Party’s Campaign Co-ordinator has agreed to support our cause!

We met this afternoon in West Bromwich and spent some time going over the issues affecting CML patients, namely the unavailability of dasatinib. We discussed, in detail, the STOP trial data, the effectiveness of dasatinib, what the TKI (tyrosine kinase inhibitor) drugs mean to CML patients, survival rates and the cancer drug fund. I told him about our campaign so far and how hard it is get our voice heard, especially by NICE, the pharmaceuticals and his own party. He agreed that it is important to ensure that all CML drugs are available to patients, free at the point of delivery. He has told me that he will do all he can to support us, he looked me in the eye and he told me that he believed in what we are trying to do.

To say I was blown away is an understatement. Tom is one of the most powerful men in politics today and I’d gone prepared; I’d even taken my box of dasatinib to show him what this is all about. He was sharp, working out quickly how much the NHS could save if the STOP trials findings are conclusive and adopted in England. These being the ongoing trials where 40% of patients who achieve CMR (Complete Molecular Remission) over a period of time come off their drugs and don’t need them again. The other 60% take the drugs again and the leukaemia goes back into remission. Hopefully you never tire of me writing about this as a cure for cancer.

So that’s it in a nutshell. Tom wants me to put a report together and propose how I want him to help out. He was sincere, friendly and genuinely interested in leukaemia and blood cancer patients. I sat in my car for 20 minutes afterwards just taking everything in, it was emotional. The implication on what we are trying to achieve is huge and having someone like Tom behind us is simply fantastic (sadly that doesn’t feel like a big enough word).

I need to start gathering research and writing up that report but in the meantime I’m sure you will join me in thanking Tom for taking an interest in a handful of poorly people and their little fight to stop a big disease. Thank you.

Kris

Tom Watson, Member of Parliament (MP) for West Bromwich East, Deputy Chair of the Labour Party and the Labour Party’s Campaign Co-ordinator, with CML campaigner and patient Kris Griffin

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