Mitoxantrone Sales Decline

Mitoxantrone is used for the treatment of metastatic prostate cancer but its sales are declining following the introduction of the new agent Zytiga.

The combination of mitoxantrone and prednisone is approved as a second-line treatment for metastatic hormone-refractory prostate cancer. This combination has been the first line of treatment, until recently, when combination of Docetaxel and prednisone has been shown to improve survival and disease-free period. So the introduction of Docetaxel has led to the initial decline in mitoxantrone sales.

Mitoxantrone is a typical cytotoxic chemotherapy agent. As with other drugs in its class, mitoxantrone may cause several adverse reactions of varying severity, such as nausea, vomiting, hair loss, heart damage, and immunosuppression. Some other neurological side effects may have delayed onset.

The fact that Mitoxantrone sales are declining further is a good sign that progress is being made in developing agents such as Zytiga which do not suffer fron these bad side effects.

FDA Approves Enzalutamide Post Chemotherapy

The FDA has approved Enzalutamide (MDV3100) for treating prostate cancer after chemotherapy has failed putting it in direct competition with Zytiga (Abiraterone Acetate).

What is surprising is the swiftness of this decision, taking only 3 months to complete their review. This is record breaking efficiecy for the FDA and shows how quickly they can respond when needed.

Enzalutamide is second to market and so will have to convince oncologists who are now familiar with Zytiga that it will provide any benefits. It is unlikely that a physician would take a patient off Zytiga who is responding to this treatment, so where does Enzalutamide fit in ?

1. Post Chemotherapy First Option
Enzalutamide could be used as the first therapeutic option post chemotherapy where it has the advantage in not having to be taken with prednisone. The Zytiga prednisone combo can then be used as a back up if the cancer becomes resistant to Enzalutamide.

2. Post Chemotherapy With Zytiga
Enzalutamide could be used alongside Zytiga and there is some evidence this may overcome drug resistance. However this would be a very expensive combination in practise.

3. Post Chemotherapy Post Zytiga
There is currently no evidence that Enzalutamide will work post Zytiga when the cancer has become hormone independent.

FDA Approves Approval Process

The FDA have approved the approval process to approve Zytiga. The FDA have announced that they have approved priority review status for the approval application to approve Zytiga for prostate patients that have relapsed on androgen deprivation therapy but not yet received chemotherapy. The priority review status means that the application for approval will be processed in 6 months, as opposed to the usual 12 months that this process normally takes.

FDA Approves Zytiga Priority Review

The FDA has approved a priority review for Zytiga use pre chemotherapy, expediting the process to 6 months from submission. The sNDA filing was made on June 16th so we should hear a decision by the 16th of December this year. The usual process takes up to 12 months for review of NDA applications but priority review status was approved by the FDA taking into account the unmet clinical needs of patients who have relapsed following androgen deprivation therapy before they need to receive chemotherapy. The submission was based on the phase 3 clinical trial data which showed positive results for Zytiga in the prechemotherapy setting.

BTG to Net 3 % Royalties on Zytiga Sales

BTG, the British Technology Group that first funded the original research into developing Zytiga, is set to receive 3% royalties on all sales of Zytiga worldwide. With projected annual sales set to reach $ 1 Billion dollars this amounts to a net income for BTG of $ 30 M per annum.

1B Benefix windfall, Zytiga sales tracking $1.2bn/year
BTG recently disclosed a further windfall royalty on Benefix, which added £10m to its revenue guidance of £200 M; Furthermore, reported sales of Zytiga by Johnson & Johnson suggest this product is on track to achieve $1.2bn sales this year. With BTG set to receive 3 % royalties on Zytiga sales it will make a significant contribution to BTG’s revenues of $ 36 M.

J&J Zytiga Sales = $ 1.2 B

BTG 3 % = $ 36 M

ICR 10 % = $ 3.6 M

RTI 10 % = $ 360,000

Zytiga sales roaring ahead

BTG’s 3% net royalty interest on Zytiga has become increasingly valuable, as the drug’s sales approach $1bn/year. J&J claims it to be the most successful oncology product launch ever in the EMEA region, and the second most successful in the US after Avastin. A high-profile presentation of Phase III data at ASCO paves the way for a filing and potential approval in the pre-chemo setting in 2013.

BTG finished 2011/12 with £113m in cash and equivalents. Revenues for the current year ending March 2013 are £190m. We consider it possible that BTG will surpass the guided fiscal 2013 figure, particularly in relation to the contribution from Zytiga. We expect a significant increase in revenues to c £224m in 2013/14 and project c 15% a year sales growth from speciality pharma and interventional oncology businesses over the next three years.

BTG has enjoyed a strong run of positive news in 2012 that has been reflected in a rising share price, up over 30% year to date. Its shares now trading at a high, last reached in 2004. Positive events this year have included the presentation of Phase III data and filing by its partner Sanofi of Lemtrada (alemtuzumab) in multiple sclerosis and the presentation by Johnson & Johnson of Phase III data on Zytiga (abiraterone) at the American Society of Clinical Oncology (ASCO). In addition, BTG has itself reported highly positive efficacy in its two VANISH Phase III studies with Varisolve, the injectable sclerotherapy for varicose veins.

Zytiga Outsells Jevtana

Zyitga sales are exceeding all rival drugs for prostate cancer including Jevtana.

The expanded indication prechemotherapy would give Zytiga an advantage as it competes with the likes of Sanofi's Jevtana (cabazitaxel), which had sales of around $50m in the first quarter of 2012 and is currently indicated for second- and third-line use in mCRPC. Zytiga sales for the same quarter were 4 fold higher at $ 200M reflecting the oncologists preferred use of Zytiga.

Zytiga is also being tested in a phase III trial as a first-line treatment for prostate cancer.

Zytiga Approved for use on NHS in Scotland

Zytiga the groundbreaking new drug for prostate cancer has been approved by the SMC for use on the NHS in Scotland. This is great news for Scottish men suffering from advanced cancer and means that they can now get Zytiga by prescription on the NHS.

CRUK says that they are delighted with the news today Monday 13 August 2012 that abiraterone (Zytiga) will be available for men with advanced prostate cancer on the NHS in Scotland.
"This is fantastic for Scottish men with the disease as it brings them in line with the rest of the UK, which has been able to access the drug since the NICE ruling back in June.
This is the second time the Scottish Medicines Consortium (SMC) – which assesses whether drugs offer good value for money – has looked at the drug, having turned it down in May. The pharmaceutical company, Janssen, offered a better deal this time around, which enabled the SMC to say yes.
This is a great decision that we’re really pleased to see. But it has been too long in coming and raised important questions about how drugs are made available across the UK. As we have said before, we need the processes by which medicines are assessed to be streamlined so that patients are not left in limbo. And we need the regulators and pharmaceutical companies to work together to get the best outcome for patients.
Abiraterone is not a cure for prostate cancer, but it can give men with the disease precious extra months of life to spend with friends and family. We’re really proud of our involvement in developing the drug, and in telling NICE, the SMC and Janssen why we think they should work together to get it approved. It is a real success story when years of hard work in the lab turn into effective treatments for patients."

Zytiga Sales Forecasts

I am expecting approval of Zytiga in the pre-chemotherapy setting in which it will be licensed for use before chemotherapy. This expands the addressable market in the US to 36,000 patients or $1.5 billion. I believe that Zytiga can capture 80% of the US market in 2014 or $1.2 billion. The European opportunity is slightly higher with an addressable market of $2.2 billion. Capturing 80% of this market could result in European sales of $1.8 million. My sales estimates for Zytiga are therefore as follows:

Sales Projections for Zytiga 2011-2015 ($ millions)
	2011	2012	2013	2014	2015
Sales ($ millions)
US	182	400	800	1,200	1,300
Europe	94	700	1,400	1,800	1,900
ROW	20	100	300	500	800
Worldwide	296	1,200	2,500	3,500	4,000

These estimates do not include other potential uses of Zytiga such as neoadjuvant therapy of prostate cancer and for treating breast cancer.

Zytiga currently has a US and European licence to treat men with metastatic castration-resistant prostate cancer who have already received docetaxel-based chemotherapy.

Janssen is now seeking a licence for the drug, to be used with prednisone, for patients who have not had chemotherapy, opening it up to more patients.

If Zytiga (abiraterone acetate) can win this new indication, that would more than double its target market according to analysts, meaning it could reach annual sales of $2.5 billion in 2013.

History of Abiraterone

1990 British Technology Group (BTG) fund a project in the UK at the Institute of Cancer Research in London working on selective inhibitors of the enzyme CYP17 as potential agents for the treatment of prostate cancer.

September 1990 Prof Mike Jarman receives funding from BTG to intitiate project.

October 1990 Abiraterone designed by Dr Gerry Potter as a selective CYP17 inhibitor.

November 1990 Abiraterone first synthesised by Dr Potter in the CRC drug development labs at the Institute of Cancer Research (ICR) within the Royal Marsden Hospital in Surrey, UK.

December 1990 Dr Elaine Barrie tests Abiraterone and finds it is the most potent inhibitor of CYP17 ever discovered.

January 1991 UK & US Patents filed with BTG.

February 1991 Abiraterone synthesis scaled up to killogram scale.

June 1991 Results on Abiraterone first presented in San Diego.

1994 First publication on Abiraterone (CB 7598) appears in the Journal of Medicinal Chemistry.

1996 Abiraterone Acetate (CB7630) licensed to Boehringer Ingelheim

1997 Phase I clinical studies start on single agent Abiraterone Acetate

1998 Worldwide Patents Granted

2000 Licensed to Cougar Biotechnology

2003 Phase I/II clinical trials intiatated

2004 Prednisone added to Abiraterone to prevent Hypokalemia (Low Potassium) side effects.
         i.e the Zytiga Prednisone Combo first used.

2005 Phase III clinical trials start on post chemo prostate cancer patients in 1,200 worldwide study.

2007 Cougar Biotechnology taken over be Johnson & Johnson (J&J).

2009 J&J use brand name of "Zytiga" for Abiraterone Acetate.

2010 J&J announce positive results of Zytiga in Phase III clinical trials against advanced prostate cancer.

April 2011 FDA Approval of Zytiga post chemotherapy.

May 2011 Zytiga launched in USA

Sept 2011 European Medicine Agency approval.

Oct 2011 Zytiga launched in UK

2012 NICE Approval for use of Zytiga on the UK national health service NHS in England and Wales.