European Zytiga Sales Increase Whilst US Sales Decline

The latest sales figures for Zytiga show that sales appear to be remaining static going from $ 265 M in Q3 to $ 264 M in Q4, but these figures conceal two opposite trends that are affecting sales:

- A decrease in US sales down from $ 136 M in Q3 to $ 114M in Q4
= reduction of $ 22 M.

- An increase in the rest of the world (ROW) sales from $ 129 M in Q3 to $ 150 M in Q4
= increase of $ 21 M.

The ROW sales increase and US sales decrease cancel out to give no overall increase in Q4 sales.

The ROW sales figures are mainly contributed by an increase in European sales where Zytiga is now available on the National Health Services of a number of European countries such as the UK and Germany.

The decrease in US sales of Zytiga is largely due to competition from the newly licensed rival drug Xtandi. Without the market presence of Xtandi the US sales of Zytiga would have been expected to continue increasing as it has been doing, but this is the first time US Zytiga sales have declined representing market share taken by Xtandi. However this decrease will probably be short lived as Xtandi's shortfalls and lack of efficacy are revealed in clinical practise. There are already some oncologist who have tried Xtandi and are now switching thier patients back to Zytiga.

Further evidence for the impact of Xtandi comes from the fact that Xtandi is only FDA approved for use in the USA and has not yet received European approval which would explain why the European sales figures have been unaffected and continue to grow.

Zytiga Q4 Sales 2012

The latest Q4 2012 sales figures for Zytiga of $264 M have been released today by Johnson & Johnson. The total sales for 2012 reached $ 961 M, just falling short of the billion dollar mark.

The 2012 sales figures for Zytiga are as follows:

Q1    $ 200 M
Q2    $ 232 M
Q3    $ 265 M
Q4    $ 264 M

Total $ 961 M

These figures show a levelling off of Zytiga sales with no significant growth over the last quarter. This may in part be due to the launch of Xtandi following its FDA approval in the post chemotherapy market. Xtandi is a competitor to Zytiga in the post chemotherapy space and some clinicians have opted to try this new treatment.

However Zytiga is now approved for the treatment of prostate cancer before chemotherapy and this is expected to double its market potential and 2013 sales may be as high as $ 2 billion.

Casodex Zytiga Combo

Casodex is a widely used antiandrogen and some oncologists are combining Casodex with Zytiga. This combination has promising potential by using an antiandrogen such as Casodex together with a hormone boisynthesis inhibitor Zytiga.

Zytiga blocks CYP17 and prevents all androgens including testosterone from being made. In the absence of testosterone caused by Zytiga the antiandrogen has a much better chance of working, since there is no testosterone to compete with its own binding to the androgen receptor (AR). So Casodex should bind better to the androgen receptor in the presence of Zytiga and so will inrease its activity as an antiandrogen.

There is also an added bonus of this combination as a result of drug meatbolism. Casodex inhibits the liver enzyme CYP3A4 which is the same enzyme that deactivates Zytiga to its inactive N-oxide metabolite. So Casodex will reduce the metabolism and clearance of Zytiga and increase its half life.

Co-administartion of Casodex with the drug Midazolam, which is a CYP3A4 substrate, showed that this increased the drug concentration 1.5 fold and doubled the half-life. This would be a useful effect when considered in context of the Casodex Zytiga combo. In practise this means that

a) The same dose of Zytiga (1000mg, i.e. 4 x 250 mg tablets) can be used for double the effect.

b) The dose of Zytiga could be reduced to 500mg (i.e. 2 x 250 mg tablets) with an equal effect.

The end result of combining Casodex with Zytiga is therefore to:

1) Increase Casodex antiandrogenic activity.

2) Increase Zytiga effects by 2-fold.

EMA Approves Zytiga Pre Chemo

The European Medicines Agency (EMA) has approved the use of Zytiga before chemotherapy throughout the EU including all member states. This follows shortly after the FDA approval of Zytiga pre chemo.

Just before Christmas the EMA advisory committee on new medications for human use made a recommendation to the EMA to approve Zytiga for use before chemotherapy which has now resulted in its European approval. This means that Zytiga is now available earlier in the key member states of France, Spain, Italy, Germany, Ireland and the UK.

Johnson & Johnson's (JNJ) Janssen-Cilag International announced it has received approval from the European Commission today that allows its cancer treatment Zytiga to be adopted in all of the European Union earlier in the treatment process.

The approved broader indication for this oral medication can now be used in combination with prednisone for the treatment of metastatic castration resistant prostate cancer (mCRPC) in men who are asymptomatic or mildly symptomatic after failure of androgen deprivation therapy but before chemotherapy.

Until now, Zytiga with prednisone has only been approved to treat men with mCRPC whose disease has progressed on or after a docetaxel-based chemotherapy regimen.

Zytiga was discovered by Prof Gerry Potter in the UK at the ICR research labs of the Royal Marsden Hospital. "This EU approval means that Abiraterone is now approved in the UK for use before chemo. This was the intended design strategy to create a drug that replaces chemotherapy so this is very good news" Prof Potter said. 

Jane Griffiths, company group chairman for Janssen Europe said. "This decision by the European Commission is hugely welcomed news. Treating men with Zytiga before they undergo chemotherapy has been shown to improve outcomes in many patients, both in terms of extending survival and in bettering quality of life."

mCRPC occurs when cancer has spread beyond the prostate to other parts of the body and the disease progresses despite serum testosterone below castrate levels.

According to Janssen, Zytiga is the only approved therapy that inhibits production of androgen, which fuels prostate cancer growth, via inhibiting the CYP17 enzyme complex present at the testes, adrenals and the tumour itself.

Abi Comes Home

Abiraterone Acetate (Zytiga) is now available on NHS prescription in the Royal Marsden Hospital where it was first discovered 22 years ago by Professor Gerry Potter in the adjoining Institute of Cancer Research (ICR) CRC Cancer Drug Development Laboratories. The medicinal chemistry research laboratory relocated from Fulham Road where it was known as the Chester Beatty Laboratories. So to keep up the tradition all new drug molecules emerging from the ICR are given CB numbers. Upon discovery this new pharmaceutical compound (later named Zytiga) was first known by its chemical name 17-(3-Pyridyl)androsta-5,16-dien-3beta-ol, and by its Chester Beatty lab registry number CB-7630. Upon aquisition by BTG CB-7630 was given the name Abiraterone Acetate which was known as "Abi" for short.

BTG licensed Abiraterone Aceate to Cougar Biotechnology who liked the number CB-7630 since it matched their own initials of CB. Cougar Biotech then conducted the key clinical trials COU-AA-301 for use following chemotherapy and later the COU-AA-302 trial of Abiraterone Acetate for use before chemotherapy.

Having secured evidence for the safety and efficacy of Abiraterone Acetate in clinical trials Cougar Biotechnology was taken over by Johnson & Johnson. This company filed for FDA approval which was granted in April 2011 and began marketing the drug as "Zytiga". The european medicines agency EMA followed suit approving Abiraterone Acetate for use after chemotherapy throughout europe in Sept 2011.

In June 2012 the UK regulatory authority NICE recommends Abiraterone Acetate for use on the NHS which allows UK cancer patients to receive the drug free on prescription.

Now at the start of 2013 Abiraterone Acetate (Zytiga) is finally available in the Royal Marsden Hospital for prescription use on the NHS to prostate cancer patients who have failed chemotherapy.

So Abi comes home...