Sometime ago, the European Crohn’s and Colitis Organization (ECCO)
found that sequential
surveys had demonstrated improving physician comfort with prescribing
biosimilar infliximab. This resulted in ECCO’s change in its position on
switching infliximab. As one can imagine, this occurs only with experience, and
often that experience is gained first by using the drugs in new patients only.
According to Ha Kung Wong, Partner, Venable LLP, physician comfort and education is still the primary determinant of biosimilar uptake, even in Europe. In his remarks at the recent ACI Biosimilar Summit in New York City, Mr. Wong emphasized that although price will enable a biosimilar to gain a foothold, it is not the only or most important factor. This is somewhat surprising; the competitive tendering system in many countries have resulted in significant price variation, including steep discounts in some locations.
Mr. Wong explained that in Norway and Denmark, Remsima uptake
has risen through deep discounts, though in other countries, discounts were far
less extreme. On the other hand, less variation has been seen with trastuzumab pricing.
Mr. Wong said, “Regardless, the uptake of biosimilars has been quite high
across the EU. For example, Samsung’s Imraldi reached 60% uptake in Germany after
only a very short time.”
He pointed out that “price does increase marketshare. But growth in uptake is still driven by biosimilar use in new patients.” Ha Kung Wong said that even in the EU, resistance to switching patients from a reference product to a biosimilar continues.
“The number 1 factor is MD resistance to switching,” he
stated, although patient resistance is also apparent. Considering the heavy involvement
of EU countries in educating doctors and patients with regard to biosimilars, more
needs to be done if systematic switching of patients to biosimilars will
contribute more fully to the industry’s success.
This experience in Europe is extremely pertinent to the situation in the US. Physicians are beset by costly administrative efforts to meet payers’ prior authorization and step edit requirements, and they may be also less experienced in the prescribing of biosimilars than their European colleagues. If the relative value of the biosimilar is not substantial enough, expect that prescriber uptake will grow only slowly. Consider not necessarily the case of infliximab, but the newest categories to likely hit the market—the biosimilars for the treatment of cancer (e.g., trastuzumab and bevacizumab). These prescribers will need some time to become comfortable with treating their vulnerable patients with biosimilars, and the requirement for use in “new” patients may not apply. It would be feasible to switch cancer treatment after completion of any cycle, as well as for recurrent tumors.
In June 2017, the US Supreme
Court ruled that the “patent dance” was not mandatory for biosimilar
manufacturers. Since then, our discussion of the patent dance (not patent litigation)
has been infrequent. The first wave of biosimilars tended to perform the dance (or
did it not incompletely). Therefore, manufacturers of drugs like filgrastim,
infliximab, epoetin, and others have already hit the dance floor or not. The
patent litigation that has resulted or been headed off (less likely!) already
occurred. Since the Supreme Court ruling, if you will, the music was still
playing, but there were fewer spectators.
I hadn’t given the patent dance much thought since that
time. I was under the impression that the majority of developers of new
biosimilars would likely now avoid this process.
An excellent session at the ACI Biosimilar Summit this week in New York City focused the spotlight on the dance floor once again. The meeting itself was chockfull of attorneys—attorneys talking patents. Inevitably, this topic resurfaced. And it caused me to alter my perceptions.
The exchange of information that takes place upon initiating
the patent dance can still be advantageous to the biosimilar maker and the manufacturer
of the innovator biologic. Irena Royzman, PhD, Partner at Kramer Levin, explained,
“The patent dance gives control to the biosimilar applicant. It limits the
number of patents the innovator can litigate. This is very powerful, especially
when the innovator has [a multitude of patents].”
However, there could be advantages for the biosimilar
applicant who decides not to participate. For instance, she said, the applicant
can keep reference manufacturers from knowing what indications are being
sought, unless these are released publicly. They can also shield such critical
information as the manufacturing process.
TAPPING IN AND
Petra Scamborova, PhD, Director, Dispute Resolution,
Regeneron Pharmaceuticals, pointed out that participating in the patent dance
does not have to be a black and white decision. “There are several options,”
Dr. Scamborova remarked, besides fully participating in the patent dance, which
she believes is still the best option for biosimilar manufacturers. “It gets
you the patent list early on,” she said, “which commits the innovator to
asserting a specific set of patents that they will defend. It also gets you the
reference manufacturing information prelitigation,” added Dr. Scamborova.
“If the innovator doesn’t abide by the rules of the dance
fully,” she continued, the applicant will be at reduced risk, which may result
in “a reasonable royalty only” should the biosimilar maker be on the losing end
of a district court decision. Dr. Scamborova also commented that full
participation in the patent dance avoids unnecessary litigation down the line.
Charles Klein, Partner, Winston
& Strawn LLP, offered another option: “dancing partway,” that is, beginning
the patent dance but electing to exit the process before completion. He thinks
this may be a viable strategy if the reference product’s 12-year exclusivity is
already expired. He noted, “It usually takes 6 to 9 months to get through the
patent dance prior to litigation.” If a
biosimilar maker intends to launch their product relatively soon after
approval, delaying the litigation by 6 to 9 months can have a material effect
on its ability to launch (e.g., 2 yr after approval).
However, undergoing the initial dance steps gains some of
the important information during the exchange. “If you elect not to continue the
dance,” Mr. Klein said, “the downside is that the biosimilar applicant loses
control over the litigation. The sponsor could decide not to sue immediately
(though not likely), which will delay resolution. You will also waive the
statutory limitations on remedies.”
From the innovator’s perspective, a partial dance is better
than no dance at all, Mr. Klein stated, “because you get a good deal of information
from the applicant’s application. You control which patents to assert and when
to assert them.”
GETTING IN AND OUT OF
STEP, DEPENDING ON TIMING
What about option 3—no dance at all? The attorneys on the
panel believe that decision again hinges on the timing of the 12-year
exclusivity. Matthew Pearson, Partner at Akins Gump Strauss Hauer & Feld,
pointed out that avoiding the patent dance altogether may be a good choice if,
for instance, the applicant is not the first biosimilar for the innovator drug.
“You may think you already know what patents will be asserted by the innovator.”
In this scenario, the biosimilar applicant can keep its manufacturing information
from the innovator company for some time.
Another important factor in deciding whether to engage in
the patent dance relates to the new biosimilar maker’s belief as to whether it
will infringe the innovator’s patents. If the biosimilar manufacturer believes it
they will not infringe, and it does not have the first biosimilar for a
particular biologic, he thinks it may make sense to avoid the patent dance completely.
What of the scenario when the opposite is true, where the biosimilar
maker is faced with 70 patents and expects to infringe on some? The patent
dance can then limit the number of patents that can be litigated. In the case
of fewer potential patents at issue, the attorneys on the panel believe that the
launch timing will play a role (along with the biosimilar maker’s willingness
to accept risk). If sufficient time exists before potential launch, proceeding
to the dance floor would make sense, they said.
Finally, in the case where the applicant knows only
partially which patents will be asserted, but assumes it will not infringe upon
any of these. Then, beginning the patent dance makes sense; the biosimilar
maker can obtain the list of patents to be defended by the reference drug maker.
It might then also make sense to stop the dance after confirming the patent
Overall, they claim, the patent dance does present some benefits for
biosimilar developers. The Supreme Court’s opinion did not strike down the
process, only the fact that it was not mandatory. Based on the opinions of
these experts in the process, it make still help smooth a still rough path
through the litigation process.