Xtandi Vs Zytiga

When it comes to comparing Xtandi with Zytiga there is no comparison - Zytiga wins handsdown on performance and price. Zytigas benefits go way beyond overall survival and there is an observable reduction in PSA levels together with a reduction in bone mets. Xtandi still has to stand the test of time in real clinical use and it will be interesting to see how it performs in this respect. Its hard to see how Xtandi will compete with Zytiga especially as it is priced considerably higher. Lets compare the 2 drugs:

Xtandi (Enzalutamide, MDV3100)
Price $7,500 per month
Oral Drug
Dose: 160 mg per day
Overall Survival Benefit: 4.8 months
Drawbacks: Cardiotoxic seizure risk
Advantage: No prednisone required

Zytiga (Abiraterone Acetate, CB7630)
Price $5,000 per month
Oral Drug
Dose: 1000 mg per day
Overall Survival Benefit: 4.6 months
Drawbacks: Prednisone coadministered
Advantage: Good safety profile and proven clinical benefits

The price of Xtandi at $ 7,500 per month is prohibitively expensive for all but the richest men with prostate cancer. The annual cost is $ 89,000 so this is aimed at the Provenge end of the market which costs $ 93,000 per treatment. However Provenge is FDA approved pre chemotherapy while Xtandi is FDA approved post chemotherapy so Xtandi would have to be paid for privately and used off-label to compete with Provenge. Who can afford to pay $ 7,500 per month privately? Not many I would think.

Will the clinicians deem the extra cost of Xtandi worthwile when compared to Zytiga ? Unlikely since this is still an experimental treatment and they may want to see more evidence for its safety.

Xtandi is a Cyano Benzene

Xtandi contains a cyano benzene group in its molecular structure. Xtandi is the trade name for Enzalutamide (MDV3100) a chemical whose real name is 4-[3-[4-Cyano-3-(trifluoromethyl)phenyl]- 5,5-dimethyl-4-oxo-2-thioxo-1-imidazolidinyl]-2-fluoro-N-methylbenzamide. So the real chemical name reveals this is a cyanide containing molecule. It also contains a thiohydantoin group which is found in insecticides which may explain its cardiotoxic side effects.

The chemical structure of Xtandi shows the cyanide group (NC-) attached to a benzene ring revealing it to be a cyano benzene derivative. This class of compounds are known to have toxic side effects and are used in weedkillers.

The drug also undergoes CYP2C8 mediated N-demethylation in the liver liberating formaldehyde which is hepatotoxic.

Xtandi is Just Another Flutamide Analogue

Xtandi the newly approved prostate cancer treatment is just another version of the existing agents Flutamide and Casodex (Bicalutamide). Xtandi is referred to as a "Super Casodex" and this is a fitting description, but this can also be looked at as "Expensive Casodex".

Flutamide usage in prostate cancer therapy goes back over 30 years and today costs $62 per month. Flutamide is activated in the liver to the metabolite hydroxy flutamide.

Casodex (Bicalutamide) is a more recent development and mimics the active hydroxyflutamide metabolite and this drug costs £432 per month.

Xtandi (Enzalutamide) has just received FDA approval and comes on the market at an astonishing $7500 per month.

So Xtandi is just an expensive version of Casodex and so far there are no clinical results to suggest that Xtandi is any better than Casodex in clinical practise.

Xtandi Cardiotoxicity Explained by Vioxx Similarity

Xtandi (Enzalutamide) has been FDA approved but comes with a seizure risk warning on the label. Xtandi has a biarylcyclopentane molecular structure that is very similar to the drug Vioxx which was withdrawn from the market due to cardiotoxic risks. The APPROVE study showed an increased risk of cardiotoxicity with Vioxx compared to a placebo and a similar trial should be conducted on Enzalutamide.

Molecular Structure of Enzalutamide (Xtandi)

Molecular Structure of Rofecoxib (Vioxx)

Rofecoxib is an anti inflammatory agent that works as a selective COX-2 inhibitor. Rofecoxib was approved by the FDA on May 20, 1999, and was marketed under the brand name Vioxx.
Rofecoxib gained widespread acceptance among physicians treating patients with arthritis and other conditions causing chronic or acute pain. Worldwide, over 80 million people were prescribed rofecoxib at some time.
In 2004 Merck withdrew rofecoxib from the market because of concerns about increased risk of heart attack and stroke associated with long-term use. Merck withdrew the drug after disclosures that it withheld information about rofecoxib's risks from doctors and patients for over five years, resulting in between 88,000 and 140,000 cases of serious heart disease. Rofecoxib was one of the most widely used drugs ever to be withdrawn from the market. In the year before withdrawal, Merck had sales revenue of US$2.5 billion from Vioxx. By the time it was discontinued in 2004, it had already caused an estimated 60,000 deaths worldwide.

Was FDA Approval of Enzalutamide Too Fast

Enzalutamide has been approved by the FDA in an unprecedented time of only 3 months and shows how fast the FDA can work when pressurised to do so. But where is the pressure on the FDA to approve Enza;utamide coming from ? Why have the FDA approved Enzalutamide so quickly ? And who gets to profit from this decision ? The normal priority review time is 6 months and can take up to 12 months to review some drugs. Have the side effects of Enzalutamide been thoroughly investigated - unlikely in a 3 month review. The cardiotoxic side effects of Enzalutamide should be more thoroughly investigated before licensing this drug.

Enzalutamide - Have You Seen the Price ?

Now that Enzalutamide has been FDA approved for prostate cancer treatment post chemotherapy it will be launched as a competitor to Zytiga - But have you seen the price ? $7,500 dollars per month ! How can that compete with Zytiga at $ 5,000 per month. Surely the manufacturers of Enzalutamide now marketed as "Xtandi" need to set a price lower than Zytiga in order to compete, and to come up with a better name !. With the dose of Enzalutamide being only 160 mg per day then they could undercut Zytiga which is used at 1000 mg per day. The cost per kilo of enzalutamide works out at $ 1,562,000 per kg, whereas Zytiga is $ 167,000 per kg and so Enzalutamide is considerably more expensive than Zytiga. It will be interesting to see how well Xtandi competes with Zytiga in clinical use.

Xtandi - What Sort of a Name is That ?

First it was MDV-3100, then it morphed into Enzalutamide only to finally emerge as "Xtandi" What ? Who ? Where is Xtandi coming from, it sounds like a second hand mobile phone but I guess the marketing guys at Medivation know what they are doing. The FDA approval of Xtandi for prostate cancer patients that have received docetaxel chemotherapy launches Xtandi as a rival to Zytiga so it will be interesting to see how they compete head to head in the post chemotherapy setting. Xtandi Vs Zytiga game on !