David's New Book

Friday, July 27, 2018

You Too, Achaogen?


I just learned that Achaogen will lay off 80 people in their research and development areas to save money. Achaogen earned its first approval, in the US, of plazomicin, an aminoglycoside antibiotic active against resistant Gram-negative pathogens.  It will probably receive approval in Europe soon. With this success, it is downsizing to focus on commercial success and sacrificing chances of following up with additional products for the antibiotic pipeline from its own R&D efforts. In their press release, the clearly cite the unfavorable commercial environment for new antibiotics as a justification for their decision.  They will continue to purse their efforts to develop a new aminoglycoside and a new, orally available B-lactam-B-lactamase inhibitor. 

Recent experience shows that all segments of the private antibiotic R&D sector are now failing. In rapid succession we have lost antibiotic research efforts in small companies like Achaogen, mid-size companies like the Medicines Company and Allergan and large companies like Novartis. All this, as Achaogen clearly notes, is due to the antibiotic market failure and society’s failure to address the problem. There is no reason to expect that Achaogen will be the last company to drop out under these circumstances. 

This will further erode investor confidence.  Any dream that many harbor of establishing public-private partnerships to further research and development of new antibiotics is crashing against the rocks of the lack of private investor interest in the current climate. 

We need to be asking our leaders (and I use the term with caution) in government what their plan is for staving off disaster. In the US, as we speak, the REVAMP bill that would provide a powerful antidote to the poisonous antibiotic market situation is languishing for lack of support in Congress.  In Europe, there is still a great deal of talk and no action. Are we waiting for the next epidemic of MRSA or VRE comes along?  Are we going to sit on our thumbs until fully resistant Gram-negative bacteria become dominant in our hospitals and nursing homes? 

A recent study from the US National Institutes of Health sounds yet another warning bell. They looked for difficult to treat cases of Gram-negative blood stream infections between 2009 and 2013.  Difficult to treat was defined as resistant to all or most of the commonly used first line antibiotics. They found that only 1% of all such infections fell into that category.  But before you accuse me of crying wolf, you need to read further. Infections caused by E. coli were the most common and the least likely to be resistant.  But infections caused by hospital and long term care pathogens like Klebsiella, Enterobacter, Acinetobacter and Pseudomonas were much more likely to be resistant. Over 18% of Acinetobacter infections were “difficult to treat.” The mortality for difficult to treat infections was 20% higher than that for more susceptible infections. While there are limitations to this retrospective study, it should remind us that without a pipeline of new antibiotics to treat resistant infections, we will continue to lose increasing numbers of patients and to spend more and more of our health care dollar trying to treat these patients rather than having the tools available to treat them effectively from the start. 

There is no excuse to further delay action to deal with the broken antibiotic marketplace and the resulting desultory state of our antibiotic pipeline.

Saturday, July 21, 2018

Everyone Hates the Pharmaceutical Industry!

I think people have good cause to hate the pharmaceutical industry. Their unreasonable prices for specialty drugs (especially in the US), their constant price increases, their political power (in the US), and their seeming disdain for the public health unless it suits their interests all make the industry, shall we say, unpopular.  When I was working at Wyeth, my biggest complaint about our marketing effort was those ads directed at consumers on television and radio. As a physician, these advertisements made my stomach turn.  I heard constant complaints by other physicians whose patients were constantly questioning them about the advertised drugs or even demanding that they be treated with those drugs.  When I inquired of our marketing colleagues, they had lots of ready-made arguments for why these advertisements were better for patients and physicians (to say nothing of Wyeth’s top line). And I have a bridge I can sell you.

Let’s try to be objective here.  Pharmaceutical companies do not exist to protect the public health and they are not charities or non-profit companies.  They exist to benefit their investors and shareholders. And, they argue, the high risk and tremendous cost ($2.6 billion and counting) of bringing a drug to market requires that they take steps to protect their bottom line. 

The industry recognizes that when they do serve the public health, it can improve their bottom line. This is clearly true for drugs that will cure hepatitis C but is manifestly not true for antibiotics.  And this brings me to the point of this short blog.

In order to incentivize the research and development of new and desperately needed antibiotics, we need to provide an attractive market for these drugs.  (See my interview with Pfizer in this regard). To do this, we will provide a prize or reward to companies who get such products approved and on the market.  This money will come from taxpayers or consumers or both.  OK.  Everyone who wants to give more money to the pharmaceutical industry raise your hands! 

And this, ladies and gentlemen, is our dilemma. If we do not fix the broken antibiotic market by providing such a prize through government action, we will run out of effective antibiotics in the next 40-50 years or so (unless we can slow the emergence of resistance further). If we do fix the market, we will be spending taxpayer or consumer money to reward an industry we hate. People in the US Congress are on a knife’s-edge here. 

I believe that if we could put this case to the population in a way that people could understand, we could go a long way to making our representatives more comfortable with this idea. We would have to deal with all the objections that we have all heard before. Why can’t the government discover and develop and commercialize antibiotics instead of the industry since we will have to pay for it anyway? Why shouldn’t we tax the industry to pay for this award? Etc., etc. 

My impression is that very few in Congress are brave enough to take the action we need to save our future. We need to clear the way for them by taking our case directly to their constituents. And we need to do this quickly and be much more effectively than we have been until now. 


Thursday, July 12, 2018

And There Goes Novartis!

News reports and personal communications from Novartis employees document that Novartis is shutting down their antibacterial and antiviral research groups.  Novartis seems to claim that this is because they have not been as productive in antibacterial research as in other areas.  While this may be true – finding new antibiotics is hard – we all know that the bigger reason is that there is no market especially when compared to oncology where Novartis has an outstanding franchise.  According to the Pew Charitable Trust, Novartis has a new monobactam in clinical development phase 2 targeting resistant Gram-negative pathogens. 

The Novartis shutdown has been a long time coming. Novartis has had a schizophrenic approach to antibiotics ever since they first established their research institute in Cambridge, MA.  They had a scientific research group, but their development and commercial groups were never happy with antibiotics. 

I don’t know what will happen to the 140 scientists and others affected by this latest catastrophe – but I wish them all well. We need their talents! 

So, among the large PhRMA players, who still has an antibiotic discovery program? Glaxo-Smith-Kline, Merck and Roche still carry out bench research to discover new antibiotics. Pfizer only has a clinical development program for antibiotics. Its probably only a matter of time for these large companies as well. 

Theoretically, any of the large pharma companies still engaged in antibiotic research or development might be available to license new antibiotics coming from biotech. But the numbers of such companies is shrinking rapidly. And biotech has struggled lately to get large pharma interested in their products.  Examples include Paratek, Achaogen and others. 

Strategically, we – society – are confused.  We keep pouring money into research carried out in small companies or academia to find new antibiotics that no one will develop or commercialize because there is no market. Ultimately, this strategy will fail unless we change course. We must fix the broken market.  Our best chance today is to support the REVAMP act now before the US congress. Call or write your representatives and get them to act before its too late!