Wednesday, February 19, 2014

Forest - Actavis?

I knew that something was going on at Forest. 

For those of you that don’t know, Forest Labs is a US-based medium sized pharmaceutical company that was most well known for selling Lexapro – an antidepressant.  But a number of years ago, it acquired the rights to a drug now called Teflaro (ceftaroline) – an intravenous antibiotic that works against some Gram-negative bacteria but also against the MRSA superbug.  To do this, they acquired Cerexa – the company spun off from Peninsula to hold Teflaro. They kept Cerexa, a company run pretty virtually, somewhat intact because Cerexa had all the antibiotic expertise – Forest had none.

Teflaro should have been a big seller.  But Forest, like many pharmaceutical companies in my experience, thought that they knew how to do things better than anyone else.  I’m not sure if they ignored Cerexa – the group they kept for their expertise, or if Cerexa was also na├»ve in the ways of new antibiotic sales. But the launch of Teflaro has to be one of the worst in the history of antibiotics.  Things are looking up for Teflaro, though.  In the third quarter of 2103 it brought in $22 million in sales. I wonder how much of that comes through their European partner, AstraZeneca (they call the drug Zinforo), and how much comes through Forest’s sales in the US.

Forest was part of the deal when AstraZeneca purchased Novexel back at the end of 2009. This deal was centered mainly around avibactam, Novexel’s broad spectrum B-lactamase inhibitor.  The combinations being pursued by both companies now include ceftazidime-avibactam, ceftaroline (Teflaro/Zinforo)-avibactam and aztreonam-avibactam.  All will have somewhat different antibacterial spectra (with some overlap), and all target different ranges of Gram-negative and Gram-positive superbugs. These constitute some of the most important potential additions to our antibacterial armamentarium in the last three decades. AstraZeneca has rights outside the US while Forest keeps the US rights.  This means that Forest deals with the FDA and AZ deals with EU and other global regulatory agencies. The two companies are tied at the ankles for key antibiotics important to the future care of patients.  They are also tied together therefore in the clinical development of all of these products. If one stumbles, they both stumble. To me, this has always seemed like a recipe for disaster in any case.

But Forest has just been acquired by Actavis for $25 billion.   If you had never heard of Actavis – you’re not alone.  From what I gather, Actavis is a Dublin (as in Ireland) – based company that mainly is involved in selling generics.  Actavis is the old generics company, Watson.  They acquired Warner-Chillcot a number of years ago. What do they know about selling branded products?  What do they know about antibiotics?  What are the implications of this purchase on the future of these key antibiotics in development? I can’t even begin to guess.  But this, coupled with recent statements by AZ management on the future of their own antibiotics franchise, leaves me trembling. We seem to by multiplying potential antibiotic disasters in an exponential way here.

So – a challenge to Actavis (Forest)/AstraZeneca – Show us how you will persevere to get these important antibiotics to the physicians and patients who so desperately need them.  Show us your way forward. Show us that this will happen.

Tuesday, February 11, 2014

Blah, Blah, Blah . . .

I apologize for the time lapse – but we were down in Columbia visiting John Quinn’s family there and the research institute where he worked with his widow, Maria Virginia. She is still carrying on the battle against resistance.  Keep your eyes on this blog for an update.

In the last few weeks, there has been some media attention to the problem of resistance.  I am ignoring the constant discussion over the use of antibiotics in animals since I consider that what needs to be done is obvious and that the FDA just has to do it. But I did want to explore some of the press recently on antibiotics for humans.

First, there is a blog by Tim Fothergill, a microbiologist, in the Huffington.  Basically he notes that we have a problem with superbugs and says he will talk about solutions in his next blog . . .

Then there was a report of a meeting at Harvard featuring some luminaries like Stuart Levy. They address the same question but stick to old tunes like stop using antibiotics (good idea but this won’t be enough) and prolonging exclusivity on sales of new antibiotics.  The latter has been shown clearly to be insufficient to attract companies back to antibiotic R&D unless they happen to have a drug or drugs with a relatively short patent life.

Finally, with a breath of fresh air, Matt Herper wrote a piece in Forbes talking about the importance of premium pricing for antibiotics.  Now we’re talking.  For superbugs, he suggests a super price!  Yes boys and girls, we will get what we pay for. If we want to be able to continue to have antibiotics that work then we will have to pay a price - as in money - ka-ching!  Anyone who tells you different is living in Colorado and smoking something.

It seems that not only large pharma, but venture capitalists as well, have figured out that the new regulatory pathways and talk of super-pricing make antibiotic R&D an attractive investment again. The old Rib-X, now called Melinta, announced a new round of funding of $70 million to develop delafloxacin. Delafloxacin is a quinolone antibiotic that is orally available (you can take a pill) and active against some Gram negatives but also against MRSA.  The problem is that, as a quinolone, you take a 40% chance that it will fail either during late stage development (phase III) or post-launch. My belief is that it is for this reason that no pharma company has jumped in to partner the drug – they are all waiting to see what happens.  But the fact that Melinta continues to be able to raise money to support the development of delafloxacin says something important about the appetite of private investors for antibiotic R&D.

At Astra-Zeneca, it seems to be the head-in-the-sand approach to antibiotic R&D. In a piece of potentially bad news (at least sad news), Astra-Zeneca announced that it was closing its site in Bangalore, India where they carried out research to find antibiotics against TB and Malaria. On the one hand, since such products are unlikely to contribute to AZ’s bottom line, we can understand this decision.  The question is – what does this augur for the rest of their antibiotic R&D in Waltham, MA and Wilmington, DE. In spite of the most promising antibiotic pipeline in the industry, they have already announced that they will focus on key areas like cardiovascular to the exclusion of non-key areas like antibiotics.  We await further developments here – but I’m worried.  It seems that the forces that are driving private investors and other large pharma companies towards antibiotic R&D are not influencing AZ’s management one iota.