PHARMA: What the Zubillaga affair may suggest, by The Industry Veteran

We haven’t spent much time over here talking about the “buckets of cash” scandal that’s been keeping the pharma-focused bloggers very busy, and even less comment on the apparently expensive and rather bizarre purchase of MedImmune. Both concerning AstraZeneca. But The Industry Veteran has been wondering around on the grassy knoll and has come up with a very interesting explanation that links the two:

I spent a good part of the past two weeks in the unaccustomed position of defending AstraZeneca. Equity analysts and others in the pharmaceutical industry seemed astonished by the high price the company paid (a 52 P/E ratio) to acquire MedImmune. Their basic criticism amounts to a complaint that AZ acquired neither an auspicious, late-stage pipeline or a significant cash flow. Both observations are correct but AZ gained other benefits for this steep price. What AZ bought was a place for themselves in two businesses when they acquired MedImmune. Companies typically have to overpay when they want to get into a new game. Ten years ago Abbott paid 40 times earnings when they bought MediSense to get into the blood glucose monitoring business. More recently Novartis paid through the nose to belly up to the vaccine business bar. A few weeks ago Schering-Plough overpaid to buy Organon but Fred Hassan gained stronger positions for himself in the women’s health and the dermatology businesses. Given the current trough in Pharma’s new product development, it’s simply a fact of life that anyone seeking to consummate a merger or acquisition must be prepared to overpay. Fifteen billion dollars for MedImmune is certainly no more outrageous than paying a 42-year old pitcher $15 million for half a season.AZ placed a toe in the water of the vaccine business, something that does not resemble Pharma’s traditional goldmine because a high proportion of vaccine customers are public agencies. Nevertheless, the vaccine business is poised to grow, and if it receives a boost from a pandemic flu epidemic, it will grow enormously. It will also grow substantially if someone makes good on the effort to develop an oncology vaccine or immunizations for the many viral infections that threaten the length and quality of life.In buying MedImmune AZ also acquired capabilities for entering the biologicals business. At this point the multi-billion dollar products of companies such as Amgen and Genentech do not face the precipitous revenue losses that occur when Pharma companies lose patent protection on their products. This is because most regulatory agencies have not developed guidelines for determining acceptable thresholds to approve generic versions of biological products. Congressional waterboys for the biotechs, such as Sen. Ted Kennedy, want makers of generic biologicals to conduct the same sort of clinical trials for their products as the original developers of the branded biologicals. Faced with such high development costs, the generic model of low cost equivalents becomes unsustainable. Nevertheless, despite the disingenuous concerns of Sen. Kennedy and others, Congressmen wise to Pharma such as Henry Waxman and Bernie Sanders will eventually succeed in creating some form of "bio similar" legislation. The country can only tolerate so many stories about people who died because they were unable to make even the co-payments on biological medications costing between $40,000 and $200,000 per year. At that point there will be a major demand for an entire industry of generic biologicals.During the two weeks I was defending AstraZeneca’s purchase, CEO David Brennan and John Patterson, the VP for Clinical Development, did their best to undermine my claims about their wise purchase.

First Brennan hinted to UK media that he might sell the vaccine
component of MedImmune. This apparently contradicted the explanation he
made to his board of directors to gain their approval for the purchase,
so he quickly denied the "rumor" a day after letting it thud to the
ground. Then Patterson took a stab at calming concerns over the high
purchase price by touting the prospects of MedImmune’s late-stage
pipeline. His public comments favorably impressed recent arrivals from
planet Mars, but few others.

While I was imputing more wisdom to
AZ’s managers than they apparently possess, they were also mishandling
a matter that made me question even their mundane, day-to-day
competence, let alone their strategic thinking. For those THCB readers
who have not been reading Ed Silverman and Peter Rost, AZ was
confronted with a situation in which one of its regional sales managers
in oncology made a tactless statement to an in-house newsletter for AZ
reps. According to this buffoon, sales reps should act as if the
offices of oncologists contain "buckets of cash" of which they might
figuratively avail themselves by making their assigned calls. This
disclosure was followed in rapid succession by revelations from several
AZ reps, together with supporting documentation, that the poorly
phrased exhortation to reps was part of a larger effort in which sales
managers were training their charges to promote products outside of
their approved indications, a direct violation of guidelines from the
Office of the Inspector General in the Health and Human Services

After reflecting on the situation for a few days, I
now think this "buckets of cash" matter is not a case of mid-level,
operational mismanagement. First of all, several companies besides
AstraZeneca are under scrutiny for promoting their respective products
off-label, i.e., for unapproved uses. Eli Lilly is alleged to
have done it for several years with Zyprexa while within the past week,
a Pfizer rep sent a letter to Peter Rost in which her company was
encouraging reps to "pre-market" their not-yet-approved HIV drug,
maraviroc. At first glance, off-label promotion that is either in the
gray zone or a flagrant violation may seem merely the usual effort to
flog more sales from available products. In a regulated industry that
prohibits marketers from telling customers that use of an
antihypertensive will make them sexually attractive, wealthy or
intimidating to adversaries, it is usual for competitors to push that
envelope. I now believe that such misdirection serves a larger, more
strategic purpose.

Robert Langreth notes in an upcoming issue of Forbes
that Novartis is making a focused effort to develop orphan drugs, those
intended to treat rare conditions. Big Pharma had traditionally
disdained such pursuits because they constitute an extreme dis-economy
of scale. Novartis, however, received a pleasant surprise from its
oncology drug Gleevec, originally approved in April 2003. At that time
it was approved strictly to treat adults with Philadelphia chromosome
positive chronic myelogenous leukemia and Kit positive, inoperable
gastrointestinal stromal tumors. From this inauspicious beginning,
Novartis subsequently gained successive approvals for Gleevec that
vaulted it into the billion dollar, annual sales league. Although
Langreth’s article did not make the claim, it led me to suspect Pharma
is seeking to "oncologize" other therapeutic categories.

oncology business within pharmaceuticals has long operated in an
altogether different manner than other classes such as cardiovasculars,
respiratory or metabolic. Based on the fact that most diagnoses in
oncology reflect a condition that is "third down and long yardage,"
formally unapproved usage is warranted. For this reason an appreciable
percentage of sales come from using products off-label. Oncologists
have good reason to suspect that if a medication works effectively
against one type of malignancy, it may possibly do so in others. So for
example, at one time 80% of sales for Taxol, the leading breast cancer
medication of the ‘90s, came off-label because the product’s sole
indication was for the far less common condition of ovarian cancer.

pharmaceutical companies the advantages of the orphan/oncology model
are manifold. To start with, the small markets for orphan conditions
offer minimal incentives to develop products and this allows those
companies who do secure approvals to charge exorbitant prices. Genzyme
makes Cerezyme for Gaucher disease and Fabrazyme for Fabry disease and
it charges over $200,000 per year for each, a simple case of making
more money by selling fewer units. Secondly, the orphan/oncology model
offers the prospect of bringing products to market more quickly and at
lower cost. Instead of conducting clinical trials on thousands of
patients at an average Phase III cost of $25,000 per patient,
regulatory agencies can grant approval to products that treat rare
conditions after sponsors complete studies on a couple of dozen people.
The key to expanding a product from an approval for treating 1,000
patients a year into a product that treats a million lies in off-label
usage. If the off-label usage that occurs in oncology as a matter of
necessity suggests usefulness in a new area, the company can slowly
decide when it becomes cost-beneficial to seek a formal indication in
that area, even as sales continue to expand.

The oncology
specialty controls this process rather carefully with institutional
tumor committees, protocols and data-driven reviews. Cheerleader reps
in short skirts and ex-jock louts who offer ski trips play a relatively
smaller role when the stakes are life and death. It remains entirely
possible that at least some industry strategists believe they can
burrow their way out of the current R&D doldrums by applying the
oncology model to other therapeutic categories. Off-label usage remains
key to this. In oncology, however, off-label uses often occur as part
of publication studies or "compendium indications" that are conducted
with some formal rigor. In the primary care categories, by contrast,
"blatantly unapproved misuse" appears as the more fitting description
of what’s likely to happen.

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