Quality of life as value
One way to answer the value question in CNS areas like depression, Alzheimer's disease, or ADHD comes from social science
as much as it comes from the laboratory. "We're in an age where patient reports, rating scales, and subjective measures are
now almost requirements," says Jonas. "A lot of [industry executives] have come out of CNS specifically because of their ability
to deal with murky, fuzzy data...it's the most difficult thing we do in our industry." Technology has made surveys and questionnaires
much easier to conduct and process, but fundamentally you're still asking the patient for a self-reported assessment. Jonas
says the "methodologies around validation have been firmed up" with FDA. Regulators may not be ready to accept every quality
of life measure as a consideration for approval, but these measures can open doors with payers, physicians, and patients.
Jonas says productivity measures like missed days at work or at school can be used as data points to establish value. But
to what extent can a caretaker scale influence an approval decision? "We're looking at some novel approaches in Europe that
unfortunately I can't talk about, but that may give us some answers," says Jonas. Vyvanse is currently approved in the United
States, Brazil, and Canada, and in January, the drug was accepted for review by the Medicines Healthcare products Regulatory
Agency (MHRA) in the United Kingdom. Vyvanse would go by Venvanse in Europe, as it does in Brazil.
Asked for an opinion on Jonas's preference for clinical value instead of p value, David Steinberg, managing director, equity
research, specialty pharmaceuticals at Deutsche Bank, said, "Well, to get approved you need a p value that is statistically
significant." True, but regulatory approval is just one of the several approvals needed for a successful brand; if payers
don't approve, for example, a regulatory approval isn't worth much. "I think the greater the value proposition you can bring
to the payers, the better," added Steinberg. On the merits of a head-to-head versus Concerta, Vyvanse for adults, and the
clinical evaluation of Vyvanse as a possible treatment for binge eating, Steinberg says the strategy makes sense. "It looks
to be a clever strategy in that they're trying to extract a lot more value out of an already approved molecule."
Differentiation as development
At ISIS and at Forest Labs, Jonas worked on products where differentiation was critical to market success, and that experience
has carried over into his work at Shire. "If you look at what ISIS did with mipomersen [a treatment for a rare genetic lipid
disorder] we differentiated into an area where there was a clear unmet medical need. That was based not only on mechanism
of action, but also on the issue of how it would be tolerated...the whole thesis was, go into an area where nothing else worked."
This strategy is similar to Jonas's decision to bring Vyvanse into the clinic for negative symptom predominant schizophrenia;
the investigational Phase II study delivered positive results in April, and was given Fast Track designation by FDA. "Most
patients with schizophrenia have residual symptoms, significant morbidity, unmet medical need...nothing really works that
well," says Jonas. "[Vyvanse] was so well tolerated at 70 milligrams, which completely defied conventional wisdom." In a statement
on the results, Dr. Henry Nasrallah, professor of psychiatry and neuroscience and director of the schizophrenia research program
at the University of Cincinnati College of Medicine, said, "If these results are confirmed in controlled clinical trials,
they would represent a significant step forward to address the unmet need of treating the negative symptoms of schizophrenia,
including a fundamental reexamination of dopaminergic and noradrenergic transmission across brain regions in treating the
negative symptoms" of the disorder.
I think the greater the value proposition you can bring to the payers, the better. —David Steinberg
At Forest, Jonas says Lexapro was "one of my programs," and "we did head-to-heads with everyone." To differentiate a product
successfully, development programs must go beyond "some loosey-goosey, let's compare two labels" kind of approach. "Every
Shire product will have a concrete value proposition. It may be quality of life, it may be return to work...we'll find some
pharmacoeconomic measure that's relatable to payers and physicians and patients," says Jonas. "I'm fortunate that our CEO
will actually let us put our money where our mouth is on this."
Jonas has a thesis—unproven—that "if you treat kids earlier [for CNS disorders], the ingrained behaviors that may be debilitating
later on don't ever develop." The question then becomes, "If you can prove it, can you claim it? It is possible, for example,
to show that productivity is enhanced by treatment." This idea raises many questions, not least of which would be the establishment
of an acceptable definition of "productivity" in this context, but there's another problem. "The one fly in the ointment for
all of this is that a lot of times you don't understand the full value of the drug until it's on the market for a awhile.
So to some extent, while all of us want to add value, it does require a certain amount of prescience on the part of the developers
to know where that value might be. And we probably lose out on some opportunities for this reason," says Jonas.