Prospects for Oral Factor Xa Inhibitors Rivaroxaban, Apixaban - Part 1 of 3: Trifecta for Sanofi?

During the past couble of months, many of you have found Pharmayst's little blog by typing in phrases like "rivaroxaban peak sales" and "apixaban sales projections" in your Google search boxes. Therefore Pharmalyst decided to start studying these compounds and found a rather interesting market. Based on what Pharmalyst has read, these drugs could easily generate $2bn-$3bn of revenues by 2011 if (a big IF given that the anticoagulation market is the a very challenging one to crack) all goes well with the current clinical trials underway.

Both Rivaroxaban and Apixaban are Factor Xa inhibitors. Rivaroxaban will probably be the first drug on the market in this class and is being developed by Bayer and J&J (which owns the US rights). They expect to file for approval in 2008. Apixaban was discovered by BMS and is being jointly developed by BMS and Pfizer.

Both Rivaroxaban and Apixaban are expected to be indicated for Venous Thromboembolism VTE (Both prevention and treatment) and for stroke prevention in atrial fibrillation. There could be additional indications like acure coronary syndrome. So how big is this market? In a word - HUGE. According to the CDC, every year, thromboembolic disease is a leading cause of mortality in the US with Actute MI leading to 171,000 deaths, Ischemic Stroke leading to 139,000 and Pulmonary Embolism leading to 29,000 deaths in 2006. Perhaps one can expect similar numbers for Western Europe.

Courtesy: JNJ Investor Relations Site

The current US anticoagulant market is estimated to be $3.1 billion annually. Looks like J&J and Decision Resources expect this market to grow to $8.4 billion by 2014....a compounded growth rate of 13%. Some of the current therapies like Warfarin and Heparins have been used for over 50 years.

Courtesy: JNJ Investor Relations Site

If Rivaroxaban and Apixaban are successful, one company that will be hurting is Sanofi, given that their low molecular weight heparin Enoxaparin, generated 3 billion euros in sales last year (it maybe a trifecta for Sanofi with Ambien going generic and Zimulti/Acomplia being rejected by the FDA).












Stay tuned for parts 2 & 3

Part 2 - Unmet needs in the anticoagulation market
Part 3 - Factor Xa inhibitors value proposition

Spirit makers take a page from big pharma's DTC ads

Hat Tip: The Daily Dish

Dr. John LaMattina's view of PFE stock

From the Associated Press yesterday:
Pfizer Senior Vice President John L. Lamattina Sells 36,066 Shares NEW YORK (AP) -- A senior vice president of drug maker Pfizer Inc. sold 36,066 shares of common stock, according to a Securities and Exchange Commission filing Monday.

In a Form 4 filed with the SEC, John L. Lamattina reported he sold the shares Friday for $26.48 apiece.

Today we hear that:

1. Pfizer Stops Developing Coley Cancer Drug

2. FDA Delays Ruling on Pfizer AIDS Drug

Pharmalyst is sure that the timing is purely coincidental (but is interesting nevertheless). These sort of setbacks coupled with other failures such as Exubera and torcetrapib are probably the reasons that Dr LaMattina is being eased out of his current position as the head of R&D at Pfizer.

PAH Drug Pricing

Recently WSJ had an interesting article regarding the pricing of Gilead's new drug Letaris for Pulmonary Arterial Hypertension (PAH).

It is estimated that 75,000 to 90,000 people in the US have PAH (half of them undiagnosed). The annual costs for various FDA approved drugs for the treatment of PAH is provided below.Interesting that there is such a huge range. Gilead claims that their drug has lower liver toxicity than rivals. Revatio (which actually is just re-branded Viagra) is the cheapest option. Given that the other drugs are priced much higher, Pharmalyst is guessing that it probably is not as effective - let me know if that is not the case because then then this sort of range in pricing can not be easily explained.

PS: Of late, several visitors have found Pharmalyst by typing phrases like "rivaroxaban sales forecast" or "apixaban peak sales" in their Google searches. Pharmalyst has been researching these products and guesstimates of sales will be the subject of a forthcoming post. Stay tuned.

GSK Consumer Division Sell Off?

Pharmagossip has an interesting post regarding some GSK investors clamoring for a divestiture of GSK's Consumer Healthcare business. Pharmalyst thinks that this might be a good idea, especially if GSK can get the kind of multiple that Pfizer received for the sell off of their consumer division to JNJ (Approx 4 times revenues. See here).

Insider (author of PharmaGossip) has expressed his view: "It could all come down to "alli" and its performance in the US.
If early sales reports are correct and lots of people suffer "treatment effects" the bottom could fall out of GSK's market!"

Pharmalyst thinks that if Alli sells well (Day one sales look encouraging), then the pressure to sell this division will be greatly amplified due to the higher valuation that this division could command.

Who could pony up that kind of cash? Some of the folks who lost out to JNJ in the bidding wars for Pfizer's Consumer division would be interested in this....though Pharmalyst tends to doubt it. GSK's consumer division is much bigger than Pfizer's and the likes of Reckitt Benckiser can't probably afford it. However there are other players like P&G, Unilever and even Novartis, who may be interested in paying that kind of change and could afford it. Another probability of course is private quity (may be this will be one of ex AZ CFO Jon Symonds' early deals)....though looks like the private equity boom is ending given higher interest rates and the likes of Blackstone trying to cash out by dumping their shares to the public.

Will be interesting to see what kind of shareholder pressure the brass at GSK will face in the coming months.

Phat Phighting with PharmaGossip

PharmaGossip has an interesting poll regarding the winner of the weight loss wars one year from now. The contestants are 1.Accomplia/Zimulti 2. Alli 3. Xenical 4. Slentrol (woof) 5. Crack

Currently Crack and Alli are winning. Pharmalyst has voted for Alli. Please cast your votes here if you haven't already. Pharmalyst's rationale for pulling the lever for Alli is as follows:


1. Accomplia/Zimulti - May not be approved in the US. Even if it is approved, there is enough concern regarding safety. Plaintiff lawyers are another force to be reckoned with here (see how Lilly is complaining about lawyer ads here).

2. Alli - Prior to fen-phen's withdrawal, it was one of the fastest drug launches...on track to generate $1b (see here). Granted Alli has worse (superficially!) side effects....however GSK will provide good DTC messaging on how these can be mitigated. If GSK's campaign is effective anyone (ranging from those needing to lose 5 pounds to those needing to lose 50) may be tempted to try Alli.

3. Xenical - Too strong a dose...and so side effects much worse than Alli. Only those really really in need will try. Past performance is best predictor of future results.

4. Slentrol - Woof! Barc! - Pfizer claims that 17 million dogs in the US have "excess baggage" (Hat Tip to Pharmalot for the phrase). Even if 0.5 million owners try this at around $300 a year, the numbers may not be enough to catch up with Alli.

PS: Congratulations to PharmaGossip and Pharmalot for being named the Top 50 business blogs by the Times of the UK.

PPS: As Pharmalyst was posting this, Pharmalot just reported that the FDA panel has rejected Zimulti.

Christopher Lydon talks to Dr. Marcia Angell

Nothing new for pharma regulars...but a few good sound bites nevertheless...

"FDA: Lapdog instead of a watchdog"

"Caduet (Norvasc+Lipitor) is like Shampoo and conditioner in one bottle"

"Pharma has bought Congress....and politicians need the money.....but the only thing they need more than money is votes."


Download mp3 here (also available on iTunes - Radio OpenSource Podcast).

Site URL: http://www.radioopensource.org

Maraviroc - "to be formally approved by the FDA on June 20"

Speaking of things premature (see previous post), is it OK to announce ahead of time that a drug will be approved on a given date by the FDA? Unless a Pfizer spokesman was misquoted, this does appear to be the case. According to this AFP article, "The new drug, which will be taken orally, is set to be formally approved by the FDA on June 20, a spokesman for the company said.". They are talking about maraviroc, Pfizer's new HIV drug which was recommended for approval by an FDA advisory panel previously. Granted that the FDA probably has informal communications with companies a few days prior to official announcements...but doesn't announcing the same to the public defeat the purpose?....maybe AFP just mangled the quote. Hat Tip: BrandweekNRX blog.

JNJ's Dapoxetine

Jim Edwards over at BrandweekNRX recently blogged about JNJ's Dapoxetine (being tested to treat premature ejaculation). This drug had been rejected earlier by the FDA. However after additional trials, JNJ plans to file for this in Europe later this year (and they will re-evaluate their US plans). Here is the money slide from their recent investor relations presentation (you can download the full set of presentations here).

A casual Google search reveals that the prevalence of this condition is anywhere from 11% to 70% with most estimates around 29-30%. JNJ reports (from an American Urological Association study) that only 4% of patients seek treatment. So this drug, if approved, could be a big deal for JNJ (if there are no safety concerns - this is a differentiated SSRI).

Also the "recreational" use segment for this will be sizeable. If this product gets approved in the US, the DTC campaigns should be interesting. While JNJ's advertising will initially start with sober clinical definitions of this condition and the need for treatment, it is only a matter of time before they take the "downward" spiral that ads for Viagra etc have taken (see here and here).

CFO Exodus

The exodus of big pharma CFOs has received wide coverage in various blogs (Pharmagossip, WSJ, Pharmalot). While the reasons for the exit of CFOs at AZ, Merck and Amgen are ostensibly known, the departure of those at Wyeth and Pfizer is somewhat of a mystery.


Wyeth is really coming out of a rough patch and it would be an odd time for the CFO to leave (good news on the HRT/Diet Pill litigation front, approval of new molecules etc). If anyone has any theories on this one, please comment or e-mail.

Pfizer's CFO's departure too is somewhat of a mystery. One theory is that this is due to the shenanigans at Pfizer India (as reported by Dr. Peter Rost). Pharmalyst agrees with Dr Rost that it does appear that Pfizer India's top brass was involved in some sort of a kickback scheme (selling a plant for $3million which was subsequently valued by Indian tax authorities at $40 million is definitely suspicious). However looks like most of the wrong doing here rests with the people at Pfizer India. Unless the CFO (who if Pharmalyst's recollection is right was not the CFO when these events occurred) was directly responsible for overseeing the sale of plants in India, it is hard to see howthis could have precipitated in the CFO's departure.

Others have speculated that Pfizer's new CEO Jeffrey Kindler is looking for a CFO with more visibility and "Wall Street" experience. Pharmalyst believes that this is perhaps the more likely reason for their CFO's departure. One pure speculation on the part of Pharmalyst is whether the CFO was forced to resign because Pfizer lost the bidding war for MedImmune? Pharmalyst has no evidence of this but Pfizer brass have expressed an interest in acquisitions (esp biologics) and looks like there was another bidder at $51 for MedImmune (which was of course beaten by Astra's offer of $58 per share). Pharmalyst wonders if this had something to with the departure of Pfizer's CFO. Let me know what you think about this speculation on Pharmalyst's part.

Novartis share of hypertension market

If anyone has some early IMS/other numbers on how Tekturna is doing, please e-mail. Looks like Novartis is making some waves in the hypertension market with the launch of Tekturna.

They also recently received approval for Exforge (combination of their Diovan and Pfizer's Norvasc molecules). Exforge may do well....What Pharmalyst has read so far from Novartis is that the combo offers better hypertension control than either component individually.

Many of these combo molecules though have one component which is still under patent (Vytorin - Zocor and Zetia, Caduet - Norvasc and Lipitor, Exforge - Norvasc and Diovan). Can anyone let me know if these things are still patented once both the constituents of the combo come off patent? If so, it will be interesting to watch the incentives PBMs offer for people to take the pills individually.