Tuesday, July 16, 2019

Q&A with Brad Spellberg - Another Point of View - Part 1

Dr. Spellberg is an old friend and a co-author of a 
recent paper (requires subscription or registration) from the New England Journal on the establishment of non-profit entities to carry out the discovery and development of new antibiotics. We recently had a far-ranging discussion on his vision of the future that I wanted to share.  To do so, Brad agreed to provide written answers to a set of questions derived from our conversation.  This will be a 2-part blog.

To start, you take issue with many “alarmists,” myself included, who think that resistance is approaching a state of crisis. Recent particular examples include nice NY Times articles by Matt Richtel on antibiotics for UTI and on the emergence of Candida auris as a highly resistant fungal pathogen. (I’ll provide links). What is your view of the resistance “crisis?”

We need to be honest with ourselves and with the public. The situation today is hugely better than it was 15 years ago, when you and Bob Moellering first alerted people to the crisis.  At that time, MRSA was exploding into communities and we had few new MRSA drugs available, and had not yet learned to reuse old drugs to treat S. aureus.  In addition, we had no new Gram negative drugs—Pseudomonas, CRE, and Acinetobacter were huge concerns, with rising incidences and rising rates of resistance.  We hadn’t had a new TB drug in half a century.  In 2004, only 6 new antibiotics were in the pipeline, and in the ensuing decade, FDA approvals fell by >90% from peak.

Things are very, very different now.  Today, 42 antibiotics are in the pipeline, and FDA approvals have tripled in the last 7 years.  Today, MRSA is a non-issue for new drug development.  We have at least 30 drugs on the market to treat MRSA.  Today, CRE is no longer an issue with respect to inadequate antibiotics, with 4 drugs approved to treat CRE, and numerous more in development including in late stages.  Today, Pseudomonas resistance rates have stabilized, and have had a new pseudomonal agent (ceftolozane) FDA approved, and others in late development. Today, Acinetobacter rates have stabilized, and we have several Acinetobacter drugs in late development.  Today we have had 1 new TB drug approved, and several others in advanced development.  Our situation with antibiotic availability to combat resistance is better today than it has been in 20 years.

That’s not to say that we don’t still have problems.  We certainly do need new oral agents to treat Gram negative bacteria.  But those patients have IV options.  And many of us have already adapted to using oral Fosfomycin to temporize the problem.

Candida aurisis almost always echinocandin susceptible and the case numbers are small.

My view is that we have a window of opportunity here to thoughtfully redesign how we discover and develop new antibiotics in a much more sustainable way.  We should stop pushing a bunch of me-too drugs to market, and a bunch of redundant drugs to market (4 CRE drugs approved, may more still in development). Pounding the table to demand that taxpayer dollars be pumped into pharma profits is not the solution.  It is neither necessary, nor acceptable to the public, and it frankly ignores much higher priority needs that the public has with respect to spending its money to support healthy people, families, and communities—such as housing, combatting homelessness and substance abuse, mental illness, and other means of counter-acting social determinants of ill health.

Why do you think that new pull incentives to promote increased profit for companies is not a good solution to the problem?  Why do you believe non-profits are a better option?

Those who are insisting that the public subsidize profits for pharma are deeply out of touch with what most of the public, and even most physicians in practice, feel and think.  The US is running trillion dollar deficits, and is already $22 trillion in debt. Our debt to GDP ratio is the greatest it has been since World War II—no joke, see graph below.

This debt is driven by several factors, but by far the biggest expenditure is healthcare, and that expenditure is projected to markedly increase in the coming 30 years (see 2ndgraph below).  Our healthcare costs now constitute a national security crisis: they are eating so much of our federal budget that there threatens to be insufficient funds for infrastructure, safety net, and military, as well as other discretionary projects.  To pretend that we can just continue pouring money into pharma companies to help them make more profit in an era of huge deficits and debt is irresponsible.

Furthermore, the public has an exceedingly negative view of the pharmaceutical industry, and overwhelmingly believes it is not only too profitable already, but that it has too much influence in politics (numerous large surveys have demonstrated this in the last several years).  To think that the public will stand for public money being pumped into profits for pharma is deeply out of touch with what Americans say is important to them, what they want, etc.  Those advocating for this approach are operating in an echo chamber—they are reinforcing their own message by talking only to the small group of people who agree with them, and tuning out the thoughts and feelings of those who don’t.

Finally, I would say, those working in the for-profit sector are supposed to be capitalists.  What kind of capitalism is it where one says, we believe in the profit motive, but when things get hard, we expect the taxpayers to cough up public money to pour into profits?  I’m actually proposing that we listen to the capital markets.  The capital markets have spoken here.  They have said, we won’t make profits in this space.

We have existing push incentives (which should be much better targeted towards unmet need) that enable companies to do their R&D with little cost or risk.  Should we also pay company profits on the backend?  If the public is fronting the R&D costs on the front end, and paying the profit on the back end, what is the company needed for?

To me, the non-profit motive is the natural response to what the capital markets are telling us.  The public will front the R&D cost, and reduce the risk.  But don’t ask it to pay profits on the back end too.

DS – but this is exactly what you will propose in the next blog. 

I don’t view it that way.  I talk about a limited, focused market exclusivity extension, one of the primary points of which is to raise funds for non profits.  To me, this is a tool to get the non-profits going more than it is a tool to retain for profits in the space.

1 comment:

  1. BS (kind of appropriate) says there are 42 antibiotics in the pipeline, but then lament that we shouldn't accept me-too drugs. Most of the 42 are clearly me-too, so how is it reassuring that the problem is being addressed? Now we are supposed to take into account all of the other problems in the Federal Budget, sit down, and shut up. Any analysis of the trajectory for resistant infections is that we are worse off and that the 'me-too' answers are not going to cut it. Then we wave the magic wand of non-profits answering the call (which is apparently not even needed). It must be nice to be the only one with all the answers.