The EpiPen Episode, an Epitaph on Epinephrine as we know it, an Epilogue and an Epiphany

EpiPen

For a good long time, economists have been thinking about the reimbursement quandary for antibiotics, esp. antibacterials. They are just too cheap, right?  Well, with the exception of HCV and some newer HIV drugs, few compounds have ever reached the stratospheric prices that oncology drugs or TNF alpha inhibitors command. Certainly very few antibacterials are in this high-price category.

Even the new crop of BL/BLI drugs with their excellent spectrum are not doing very well in the market place (according to recent IMS data for Zerbaxa and Avycaz).  Keeping these drugs restricted and requiring special approval by ID is appropriate if we don’t want them to become overused and obsolete in record time. But this regulated environment cuts into profits, and profits are the life blood of Big Pharma. Pharma CEOs follow Sutton’s Law and go for other therapeutic areas, “because that’s where the money is”.  We can’t blame them for behaving like the capitalist over-achievers that stockholders demand.

At a time of rampant MDR infections, the current situation is a lose/lose for patients and society. Yes, there was Cubicin, the poster child of an antibacterial that could make money, but its market success has not been replicated by others. Maybe sales for one of the newer tetracycline derivatives will take off, maybe solithromycin can be commercially successful as IV/PO drugs with a useful broad spectrum. The same is less likely to happen for an IV only drug like plazomicin, hamstrung by its aminoglycoside ancestry of renal toxicity or rather for a pure / poor Pseudomonas-only drug as recently discussed at FDA.

Many colleagues believe that the value of antibiotics should be ‘reassessed’ reflecting the benefits they provide to the individual patient and to society as a whole. They believe that prices for antibiotics should be much higher, compensating for use restrictions and reflecting the curative action of a short-course regimen. There is some truth to this argument, but we may want to consider an altogether different approach as well.

Maybe the ‘value proposition’ (a euphemism to justify price hikes) for antibiotics does not need to change. Arguably, the recent trend for ever-higher pricing of many other drugs, which has resulted in absurdly high costs for ‘specialty medicines’ that command phenomenal prices often for little gain, has distorted the market; it is this trend that really drives antibiotic development out of competition. When an EpiPen which is nothing but generic epinephrine in a nice injector, can be priced at $600 or more, and when Mr. Shkrely can jack up the price of Daraprim overnight, or … (fill in your favorite overpriced medicine), something is seriously wrong.

No wonder, the US is the most lucrative prescription medicine market. Only here the taxpayer pays outrageous innovator prices for yet another insulin (hey, it is still injectable last time I checked!), and allows companies to market drugs at prices unchallenged by review and added value. This model works best with drugs for chronic illnesses, as the price effect accrues over time in a more insidious manner.

Why would anyone want to do antibiotic R&D? VCs do it only because BARDA and IMI are providing non-dilutive funding; Big Pharma makes a token effort because it is good for image. In former years, antibiotics were a core therapeutic area at many large pharmaceutical companies; those days are gone.

There was, indeed, a time, not too long ago – thinking back to the 80s and 90s – when antibiotic prices were much more in line with those of other drug classes. Even though few antibiotics reached the blockbuster stage of > $1 billion in yearly sales, few other drugs did either. Developing antibiotics was an attractive proposition: a lower ROI was offset by lower overall investment cost, better predictive early data, and an overall lower risk of failure.

With the advent of PK/PD in the past two decades, antibiotic development could actually be streamlined even further, reducing costs and time to market. However, FDA successfully blocked this from happening by heaping way too many new requirements on anti-infective developers, more so than in any other therapeutic area, thereby making antibiotic development expensive for less reward.

So, the AI field lost out: the advances in PK/PD benefits just did not compensate for all those new regulatory hurdles. At the same time, Soliris from Alexion and specialty products from companies like Genzyme have opened everyone’s eyes to the wonderful new high-price world of orphan drugs. Combined with fancy patent extension footwork, late introduction of new formulations to prevent generic erosion, maneuvers to avoid a patent cliff by paying competitors for delayed entry, the field has matured into one of unadulterated greed and profit maximization. Antibiotics have lost out in the development world which knows no middle class, where only the top money-making indications have a chance of continued corporate funding, at the expense of pretty much everything else.

What is the solution? Contrary to what is often said about Push and Pull incentives to rekindle antibiotic R&D, let’s level the playing field and propose a cap on the reimbursement by CMS of excessively expensive drugs. Drug prices have gone through the roof and are seriously threatening the entire US health care system. We need to get rid of the insane unrestricted pricing of drugs at some time anyway before the reimbursement system goes bankrupt. It is time to wrest control over pricing from companies.

There is zero justification for the current price of the EpiPen, or for Shkrely’s Daraprim price hikes. Neither is there for the $90k a pop for Harvoni or some of the other HCV drug cocktails from Gilead and Abbott. We need a NICE committee like they have in the UK, before drugs can enter the market priced to impoverish the system. Drug pricing has become too toxic for society and the social networks.

Nobody would expect companies to clean up their act and reign in drug costs themselves; they would rather stick with the current model until the last red cent has left the federal coffers. It is time for our legislators to stop this out of control greed.  It is time for us antibiotic-loving academics in ID to cut ties with industries that overcharge for new antivirals and engage in frivolous exploitation of a Health Care system that is about to go broke.

Academics are not savvy enough to see the writing on the wall or to understand the sales tactics of marketing departments. Academics on the Speaker’s Bureau and Guideline Committees are not providing the full story when they only speak about Safety and Efficacy but not about toxic drug prices. Academics that advocate higher prices for new MDR antibiotics and ever more government incentives are not credible agents of change.

Epinephrin for injection is available as a 1 mL solution in a single-use clear glass vial which contains 1 mg epinephrin / mL; hence, 0.3 mL = 0.3 mg = the dose to inject i. m.

What we need are significantly lower prices for all extravagantly overpriced medicines, price controls and better checks on anti-competitive practices.

As for the EpiPen situation, why not buy a few vials of epinephrine or adrenaline, a few syringes and needles, and maybe some vials of sterile D5W. The adult dose is 0.3-0.5 mg IM. You could even ask your neighborhood pharmacist to package up preloaded sterile syringes for ready use that have a shorter shelf life but cost a smidgeon of an EpiPen and could be made for little expense right around the corner.

Well, you are out of luck: FDA would not allow this as a matter of principle. They say they want to protect you, but as the EpiPen episode and others like it show, regulatory hurdles also protect the price gouging industry from competition. When regulators set the bar too high for EpiPen competitors, they are supporting monopolistic behavior.

Maybe it is time for end users to fight back…

 

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