In a busy beginning of the week, the US Food and Drug
Administration approved new biosimilars for Humira®and Rituxan®. Samsung Bioepis gained approval for Hadlima™
(adalimumab-bwwd), and Pfizer scored with Ruxience™
(rituximab-pvvr).
HADLIMA
The approval for Hadlima covers the following indications:
Rheumatoid arthritis
Juvenile idiopathic arthritis
Psoriatic arthritis
Ankylosing spondylitis
Crohn’s disease in adults
Ulcerative colitis
Plaque psoriasis
Formerly known as SB5, Samsung Bioepis secured Hadlima’s approval
on the basis of phase 1 and phase 3 studies in rheumatoid arthritis.
The phase 3 investigation included over 500 patients, finding ACR20
responses to be equivalent to that of Humira (at 72%). Immunogenicity profiles
for the two agents were also similar through 52 weeks of a switching study.
According to its licensing agreement with Abbvie, manufacturer of Humira, Samsung will not be able to market this agent until end of June 2023. This agent joins Samsung’s two other approved anti-TNF biosimilars, Renflexis (infliximab) and Eticovo (etanercept). Only Renflexis is currently marketed in the US.
RUXIENCE
Pfizer’s newest biosimilar entry, Ruxience, has been
approved for a subset of indications of reference product Rituxan, including:
Treatment of adult patients with relapsed or refractory, low-grade or follicular B-cell non-Hodgkin’s lymphoma who are CD20-positive and have failed prior treatments
Patients who have nonprogressing, low-grade, CD20-positive B-cell non-Hodgkin’s lymphoma and who are stable after receiving a prior chemotherapy regimen containing cyclophosphamide, vincristine and prednisone
Patients with CD20-positive follicular lymphoma who are therapy naïve in combination with chemotherapy or who had responded to previous rituximab therapy
Patients with CD20-positive chronic lymphocytic leukemia in combination with fludarabine and cyclophosphamide
Granulomatosis with polyangiitis in adult patients in combination with glucocorticoids
The biosimilar does not include Rituxan’s labeled indication for rheumatoid arthritis, similar to the other approved rituximab biosimilar.
The application for Ruxience included the results of the
phase 3 clinical trial (REFLECTIONS), which included
394 patients with follicular lymphoma. Compared with the EU-licensed version of
rituximab (MabThera®), Ruxience was found to provide equivalent
clinical and safety outcomes.
Originally designated PF-05280586, Pfizer has not disclosed when Ruxience will be available. Pfizer signed a settlement with Roche (Genentech) over litigation for a key Rituxan patent, but terms of this agreement were not disclosed. The other FDA-approved biosimilar competitor in this space, Celltrion’s Truxima®, is similarly awaiting launch.
$44 Billion by 2024. $250 Billion by 2024. Whatever. I’ve not been very impressed by the many attempts to estimate how much money biosimilars could save the US health care system. Even the more well-known estimates of biosimilar savings, like those from RAND and Express Scripts, have been little more than games of “pin the tail on the donkey,” as the researchers were blinded as to when products would actually launch and the unproved potential for biosimilar uptake.
Of course, this was not the economists’ fault. They had little past information about the US biosimilars market on which to base their view of the future, and they could not have predicted the extent to which patent litigation prevented access to these medications.
I do appreciate the latest effort, however, by the Biosimilars Council (a subsidiary of the Association for Accessible Medicines) to understand biosimilar savings. Instead of predicting the future, the Council reviewed the past to assess how much each biosimilar would have saved the health care system and patients had they launched as expected.
The number they landed on was $7.6
billion since the introduction of the first biosimilar in 2015 through
2018. It applies not to the seven biosimilars (as of June 12, 2019) that were
launched but to the 12 that were approved but not available because of ongoing patent
litigation.
As impressive as this lost opportunity sounds, I believe that the biosimilar savings estimate is still too low. The calculation by the Biosimilars Council does not seem to include an important aspect: The reference manufacturer takes significant price annually for each year biosimilar competition does not emerge. The analysis assumed a 30% price discount and 40% uptake, split between two biosimilar competitors. Uptake was assumed to increase to 50% if three were three separate competitors. Yet the analysis was based on actual list prices from IQVIA data.
If biosimilar competition existed, these price increases would not have occurred, likely at all. For example, the availability of Inflectra® and Reflexis® did not fuel great uptake of biosimilars at the expense of Remicade®; however, the infliximab market was changed suddenly, by forcing Janssen Biotech to not only halt their price increases in 2016 but significantly lower their net pricing. As a result, average sales prices have been dropping ever since the introduction of the biosimilars (from a high of $85.81 per 10 mg in January 2018 to $69.96 in July 2019 [–19%]).
Consider the same scenario for the adalimumab biosimilars, which I wrote about previously. Without competition, AbbVie can raise its retail prices right through 2022, resulting in upwards of 50% higher list prices. Although this does not account for contracting, each new payer contract it should be remembered, is based on the current price (not the previously rebated costs). In other words, the higher prices work their way into subsequent payer contracts. How much additional biosimilar savings, on top of the calculated $7.6 billion, would that be? I’m not an economist, but it shouldn’t be too difficult to estimate, based on no future price increases (only future price reductions). Over an 18-month period, Amgen raised the price of Enbrel® four times, resulting in a 37% jump by 2016. Had biosimilar etanercept been available at the time, that would not have happened, yielding an instant 37% savings. That does not prevent the reference manufacturer from hiking the drug price in the months before biosimilar competition occurs. This practice is expected to continue. However, the earliest possible availability of biosimilars will yield compounded price savings.
On May 7, the Senate
Judiciary Committeeheld hearings
on how to clear the patent thickets obstructing access to lower-cost
biosimilars. One of the key avenues raised during the hearings was moving the
Federal Trade Commission (FTC) directly into the fray. We asked Kevin M. Nelson,
our go-to expert on intellectual property issues, for his take on this
possibility.
Biosimilars Review
& Report: Kevin, thanks for trying to help us sort out these issues!
Let’s set the stage first: Has the FTC dipped their toes into intellectual property
(IP) and patent issues in the past?
Kevin Nelson, Esq:
The way you phrased the question is appropriate. Yes, they have dipped their
toes into patent issues a little bit. It’s sort of a dicey field for the FTC.
Kevin M. Nelson
To provide a bit of background, two matters come to mind. The first, Federal Trade Commission v. AbbVie, had to do with Androgel®, where the FTC alleged violations of section 5 of the FTC Act and sham litigation. This is usually a civil cause of action brought by generic companies. (Sham litigation is a form of anticompetitive litigation that is “baseless or otherwise without any legitimate foundation.” It is usually a delaying tactic to prevent product competition for extended periods of time). Antitrust violations can be difficult to prove, so sham litigation, which can also be a high hurdle, is sometimes alleged. Interestingly, in the Androgel matter, the FTC’s decision did make it past the District Court level, but I believe it is currently on appeal. But there was a large disgorgement ordered by the District Court in the $500 million range. One of the primary things the Commission said was that the lawsuits filed delay competition, and those lawsuits were objectively and subjectively baseless. So the FTC did wade into the patent issue.
The second was Federal Trade Commission v. Bristol-Myers Squibb, which involved BuSpar®. In its investigation, the FTC found that there was not only false listing in the Orange Book but false statements to the US Patent Office by Bristol-Myers Squibb, and also baseless allegations of patent infringement.
So the FTC has dipped its toes in the water in evaluating
the patent issues and the merits of patents as part of its jurisdiction of
looking at whether there is anticompetitive injury. The focus has been more in
the FTC Act versus one of the traditional antitrust acts.
THE FTC’S AUTHORITY IN PATENT DISPUTES
BR&R: Will legislation
be necessary to provide the FTC the necessary authority to investigate patent filings
that hinder competition?
Nelson: The FTC
already does have the authority to bring causes of action where there has been
unlawful use of patent rights in order to delay or harm competition. That’s the
FTC’s mission—to protect competition. If there is any action to harm
competition, the FTC has the tools to address that right now. The Androgel matter
is a perfect example. The FTC used the FTC Act, not the Antitrust Act, but the
result was the same—a significant disgorgement of profits, which is the penalty
that we as consumers would want to occur if someone was abusing their patent
rights.
BR&R: One way
the FTC may intervene in the biosimilar patent thickets is to focus solely on
the expiration of the composition-of-matter patents when deciding on the timing
of a biosimilar launch. Might this start us on a slippery slope? In this case,
the Commission would disregard patents involving new formulations, new manufacturing
processes, new indications, etc, as a separate, less-essential group. We’re not
talking necessarily about invalid or obfuscating patents per se.
Nelson: It will
be interesting to see exactly what the legislative proposal will say. Right
now, it’s a bit unclear.
The first problem that we’re seeing, is that the FTC has the
tools to act, but these tools can only be used after the fact, or after
competition has been harmed.
Problem 2 then becomes, if we try to do something before the competition is harmed (or to prevent this harm) and we allow some patents to be asserted, we will be getting into constitutional concerns. If you bring lawsuits based on patents, is that a violation of Takings Clause? [Editor’s Note: The Takings Clause is found in the Fifth Amendment of the Constitution, and prohibits the government from taking personal property without just compensation.] A product may be protected by subsequent, legitimate patents; we can’t prejudge that.
The Constitution prohibits the government, at least right
now, from saying that “you cannot assert these patents.” That also relates to a
petitioning or free speech issue. If I file a lawsuit because I have a patent, and
the FTC says I can’t file that lawsuit, does that interfere with my free speech
rights? The answer is yes, unless your lawsuit was objectively and subjectively
baseless.
That’s where we get into FTC’s dilemma now. It will be very
interesting to see the remedies that will be proposed, especially since there
may be better avenues out there.
DOES THE FTC NEED NEW LEGISLATION TO ACT?
BR&R: It
sounds like the FTC doesn’t lack the authority, but legislation would have to
be passed to further define how it can enforce this authority.
Nelson: I don’t
know that we need new legislation to further define the FTC’s authority, rather
there needs to be direction in terms of their priorities. The FTC could enforce
these issues, but that has been low on its priorities.
For example, the Commission have been very active in the
pay-for-delay area. A lot of their actions are the result of anticompetitive
acts that took place in the early 2000s. We’re not seeing much action today where
the government is trying to punish companies for wielding an unfair number of
patents—where many of them are improperly issued or should not be enforced at
all. That needs to be more of a policy focus or objective of the FTC.
BR&R: Assuming
the FTC does get involved more proactively in policing anticompetitive patents,
do you think that might affect drug manufacturers who intend to seek new
formulation/manufacturing patents and others in the future?
Nelson: The hope
is that innovator companies would be careful in the types of patents that they
pursue and try to enforce against potential competitors. Because there hasn’t
been much enforcement in this area, we are seeing these 100-patent assertion
cases, which put a strain on resources. In some companies, we are seeing less
emphasis on a strategy of innovation and more on creating these patent thickets
to delay competition. In several open forums, the FTC has actually expressed
this view. And that’s not what we should be focusing on as a society. They should
be focusing on the next generation of life-saving therapies, not putting a
protective wall around older agents.
If the FTC is more willing to go after companies that are
enforcing a lot of these improper patents, the manufacturers may actually start
to refocus on innovation.
BR&R: When do
you think the rubber will meet the road? Will the FTC be pushed in this
direction?
Nelson: I think
we will see that legislative proposal. The better focus is on things that have an
impact on consumers, innovation, and competition. We do need legislation that
limits or prohibits product hopping or product shifting; that’s a real concern
and can be addressed. We can limit use of products that are “second-generation”
and have no additional clinical benefit to patients over the original product.
If there is no clinical benefit to the patient, then we shouldn’t be giving
them exclusivity. That takes companies away from the incentive to protect old
products and move them toward creating new innovative products.
I think a policy shift for the FTC, rather than a
legislative shift, will encounter fewer obstacles.
In the biosimilars arena, at least in the US, history seems
to be truncated. Policy changes occur in rapid fire succession these days, and
access scenarios don’t evolve—they just happen or they don’t! Along this brief
journey, I’ve taken the opportunity to focus on some of the sign posts that
were exceedingly poor maps for navigating the future.
One of the first blogs I wrote for The Center for Biosimilars in early 2016, involved a defeat for Amgen in its patent litigation with AbbVie regarding Humira®. No one was sure what the implications of this decision would be. Amgen was on the road to gaining approval of the first biosimilar adalimumab. The payer and investment community sensed momentum building towards the imminent takedown of the number 1 biologic in terms of sales. I referenced 2016 Humira revenue estimates of $14 billion for AbbVie, and mentioned two other prospective biosimilar makers—Baxalta and Momenta—being hot on Amgen’s heels.
In that same article, many in the investment community was under the belief that a US marketed adalimumab biosimilar would be available by 2020. Instead, January 2023 is looking more inevitable. I wrote, “The investment community believes that Amgen will come out on top; they believe that AbbVie will have $6 billion—not $18 billion—in Humira sales by 2020.”
I’m not sure that I could have been more wrong in my
assumptions or sentiments, thinking that AbbVie’s maze of 70 patents (at the
time) could be severely damaged at that time by the process to challenge patents.
This may happen today through Boehringer’s efforts, but I wouldn’t count on it.
The other major players don’t have the stomach for fighting this battle.
In 2017, Baxalta and Momenta have dropped out of the biosimilar contention for Humira’s marketshare, replaced by Sandoz, Boehringer, Coherus, Samsung Bioepis, and perhaps others. Baxalta and Momenta , one being taken over by Shire and the other facing financial realities.
Unfortunately, it will take a miracle, in the form of a Boehringer victory or even less likely, adoption of Dr. Peter Bach’s biologic pricing proposal, to get adalimumab to the payer market. The fact that the proposal that Dr. Bach and his colleagues at Memorial Sloan Kettering laid out received as much attention as it did tells quite a bit about our serious frustration today with access to biosimilar savings.
Of course, very few actions taken by the current Administration have yet to be implemented. These are intended to bolster the biosimilar industry and move from promised to actual savings. However, the signs are telling me that we’re not in an evolutionary phase of biosimilar development–an extinction event may be around the corner.
In May 2016, I interviewed Steven Avey, Vice President, Specialty Pharmacy, MedImpact, for the Center for Biosimilars. That conversation speculated on the potential for biosimilars, having only recently experienced the launch of the first biosimilar in the United States, filgrastim-sndz. At the Academy of Managed Care Pharmacy’s 2019 annual meeting last week, I sat down with Steve once again to gain his perspectives on changes in the biosimilar environment.
Biosimilars Review
& Report: Congratulations on winning the Academy of Managed Care
Pharmacy Foundation’s Steven G. Avey Award! This is sort of a double honor,
first having the award initially named after you, and then many years later,
winning it yourself!
Steve, you’re considered one of the real thought leaders in
managed care pharmacy. What do you consider to be the main challenges facing your
colleagues today?
Steven Avey, PharmD: Thank
you. There are many real challenges today. First of all, we have the potential
for drug rebates to go away. It’s clear that something is going to be done (and
we don’t know what that is), and it could apply not
only to Medicare Part D, but possibly Medicaid and commercial. We will need to
wait and see.
Steven Avey, MS, RPh
Another challenge relates to the Administration’s emphasis
on reducing list prices for drugs. This will not only influence the industry,
but managed care pharmacy as well.
That challenge is part of the ongoing concern about the cost
of specialty medications (and continuing price increases), and the greater call
from payers for a better understanding of the value that they’re getting from
these medications. Are the people who are taking specialty medications actually
getting real benefit?
BR&R: In
addition to payers, employer purchasers and others have been requesting a
better understanding of the value of specialty medications. This has been
sought for 10 years or more. Are we any closer today in getting a grip on this?
Avey: I think we
are. Many PBMs are getting more involved in data management regarding these
medications. The better we get at analyzing the medical and pharmacy data
together, the closer we will get to understanding the value of these specialty
medications.
To give you an example, a PBM today is basically reviewed
and assessed on what its financial picture looks like—are you able to bend that
specialty cost trend? But if you don’t know what these specialty agents are really
doing for the patient population, how can you tell if covering them is the
right thing to do? In order for us to know that, we have to evaluate the
medical and pharmacy data together and focus on the total cost of care of that
individual member. Over time, you can say that our costs are either going down
or not. Then, we can ask the question, am I using the right agent or should we
be using those very expensive drugs for these patients?
Given the lack of the medical and pharmacy data, we just
don’t know. That’s one of my greatest frustrations.
BR&R: Let’s
switch to biosimilars. Do you believe that if the rebate safe harbor is removed
for Medicare, payers will also stop seeking them?
Avey: Yes. It
will definitely trickle into the commercial side. I can see a day in the not
too distant future where we don’t rely at all on rebates. It will be a new
world focused almost solely on list price reductions.
BR&R: Will
that give biosimilar manufacturers an edge?
Avey: It will be
a boon for biosimilar makers! When the rebate goes away, then all that remains
is the list price. That will be a huge advantage for biosimilars.
BR&R: Well,
if I’m a reference biologic maker, whose R&D costs were paid off a decade
ago and whose profit margin is extremely high, I can still lower my WAC price
considerably to compete with the biosimilars, right?
Avey: They can,
but they will have to compete with three or even five biosimilars who do not
have to spend millions of dollars on advertising or promotions like the
innovators do to keep their brand’s exposure and visibility high. The innovator
drug maker will do everything possible to avoid losing that high market share.
Now, I haven’t seen much of this in print, but payers are
angry—they’re angry at these 10% to 20% increases in costs each year from the
innovator drug manufacturers. As a payer, if a biosimilar is available, why would
I want to support that innovator maker, who has
dramatically raised costs for the last 10 years? That gives biosimilar
manufacturers the advantage: “Hey, I’m the new guy helping you to reduce costs.
How about supporting me instead?” I think many payers will act on this message.
BR&R: In our
conversation in April 2016, that was the gist of what you said.
Avey: And I
haven’t changed my mind.
BR&R: I
asked, how soon are you going to drop the AbbVie contracts (when there was some
expectation that biosimilars would be available before 2020), and you said, “As
soon as humanly possible.” And you weren’t the only one who said this.
Avey: Absolutely.
And now the timeline has been extended to 2023. This just made us all the more
angry, because this is because AbbVie filed 100 patents on Humira®,
which overwhelmed what the BPCIA was intended to address. The result is that AbbVie
is going to make $16 billion a year (and more each year) for 4 more years
before we’ll be able to see some competition for their market.
BR&R:
Genentech (Roche) is coming out with subcutaneous forms of Herceptin®
and Avastin®. Will these introductions change the way you position the
biosimilars for these two cancer agents, when they are finally launched?
Avey: We’ve dealt
with this 15 years: It’s really no different than what we’ve seen occur with conventional
agents. Consider a sustained-release form of a brand that is approved around the
time the generic for the immediate-acting formulary is launched. You look at
the new product and ask, what does that premium in pricing buy us? Is it a
site-of-care advantage? Maybe, but does it really offset the cost of using that
more expensive agent? We generally decide to cover the lower-priced (albeit it
not as convenient) dosage form. With biologics, the cost differential between
the new agent and the biosimilar is very large, and there is very little
advantage for the new subcutaneous formulation.
BR&R: We are
seeing something similar playing out right now with pegfilgrastim. Most of the
market has moved to the use of Amgen’s on-body injector OnPro®, and
the biosimilars are being launched using prefilled syringes. To the extent that
payers are interested in eroding OnPro’s marketshare, assuming the price
difference is substantial, OnPro does represent a bit more patient convenience.
Some payers may be thinking this way. To the extent that this will happen may
predict some similar effect for the trastuzumab and bevacizumab markets.
Avey: You have to
remember that payers are receiving a lot of criticism that we’re not doing a
good job of supporting the biosimilars. Quite frankly, the biosimilar drugs
that have been approved up until now are really covered under the medical
benefit. We have a little trickle that can be covered under the pharmacy
benefit. Payers have only so much bandwidth. They know that under present
conditions, a new biosimilar has to build market share from scratch. Some have
said, “You know, it’s not worth the effort. We have other fish to fry. We’re
not going to get too excited yet about these products.”
We have an HMO client that did an amazing job moving market share
away from Neupogen® to Granix®. But they own their
prescribers and they can easily analyze the combined medical-pharmacy spend.
They saw a dramatic lowering of expenditures.
BR&R: Are you
expecting biosimilar products for trastuzumab and bevacizumab to be managed
under pharmacy?
Avey: We see
those drugs under the pharmacy benefit now. Remember that those drugs have a
greater utilization than the other biosimilars that have been launched to date.
I do think that they will attract a lot of attention. And if the rebates do go
away, that takes the market share question right off the table. The biosimilars
will do quite well.
BR&R: The
four-letter suffixes: The FDA recently came out with an updated guidance,
saying that the agency will no longer consider adding four-letter suffixes to
previously approved reference agents. However, they will continue to add
suffixes to newly approved biosimilars and interchangeable agents.
Avey: Everybody
is trying to figure out what’s next here. When we look at biosimilars’
pharmacokinetic information, one biosimilar is going to be somewhat different
than another. I don’t think it will be an insurmountable problem, but just a
headache. We’ll just have to be more in synch with our specialty pharmacies to
ensure that they stock and dispense this one biosimilar with this one
four-letter code.
BRE&R: Have
we made any progress from an educational standpoint here? Do providers and
patients still think that a product with a four-letter code is not comparable
to the originator brand? What is the level of discomfort today?
Avey: I’ve
watched this carefully over the last year. I don’t think there will be huge
angst from the payer. The prescribers and to some
degree the patients that will need more educating to make them feel more
comfortable. We will need better educational materials and communications for
them.
The situation is really no different than when we started instituting
the generic substitution laws. We heard a lot of claims that docs will never
prescribe generics, patients will never take them. We had to do a lot of
educating to alleviate their fears, and to help prescribers understand that
these drugs work like the brands work. At the end of the day, I don’t think
that this will be a long-term challenge.
Only Boehringer Ingelheim remains as a biosimilar maker who
has an approved version of adalimumab but who has not signed on with AbbVie.
United Food and Commercial Workers Local 1500 has filed the suit with the other
manufacturers and AbbVie, claiming that by their actions, they are trying to “divide
the market for adalimumab between Europe and the United States,” according to
the Center for Biosimilars report.
This is an interesting question. The individual motivations of the first companies to come to agreement with AbbVie (Amgen, then Samsung Bioepis) included an end to interminable patent legislation in the US. They wanted the ability to immediately plan launches in Europe (starting in October 2018). The motivations of most other subsequent signees almost certainly was to not forfeit marketshare in Europe, which was needed to help sustain biosimilar development efforts for the US market. In fact, many of these prospective US manufacturers already had received approval in the EU.
AbbVie’s principal patents on Humira® expired in Europe in October 2018. The last of the principal patents are supposed to expire around 2023 in the US anyway. Was it necessary to arrange serial US launches as demonstrated in this link? Would patent litigation have continued well past the supposed patent expiration date? Knowing AbbVie, this is likely. Their several patents involving adalimumab use to treat individual diseases would provide AbbVie a basis for forging ahead with lawsuits that would have gained them additional billions of dollars in sales while the suits meandered toward conclusion.
Does this mean that access to Humira is accelerated through the signing of the royalty agreements, rather than delayed through acts of collusion? That is difficult to say. Although should the lone holdout—Boehringer Ingelheim—decide that it makes business sense to launch at risk, it could topple the carefully orchestrated structure of the agreements. Amgen believes that it will launch the first adalimumab biosimilar, and experience a few months of exclusivity in the US. At that point, Amgen (and every subsequent adalimumab biosimilar maker) would have to decide whether (1) to do the same or risk losing its advantage, (2) start working towards marketing plan B, or (3) cede the initial marketshare and its billions in revenue and wait it out. If Boehringer obtains its sought after interchangeability designation, that may well speed up the process.
Personally, I find it hard to believe that these individual
acts represent premeditated collusion; although the resulting lack of access to
the many biosimilar versions may look to others as an orchestrated maneuver.
In the absence of really big biosimilar stories with far-reaching implications, let’s start with some interesting bits on biosimilars to begin this week.
First, insulin maker Eli Lilly asked the Food and Drug
Administration a very interesting question, in comments
on the agency’s guidelines on transitional drugs. Lilly requested clarification
of the rules under which it might introduce an authorized brand of insulin
(that is, a lower-priced version of an existing insulin brand). The insulins
are one group of medicines that is scheduled to transition to regulation under
the Public Health Services Act in 2020, and thus be subject to formal biosimilar
competition.
Second, Boehringer Ingelheim, which received FDA approval to market its adalimumab biosimilar Cyltezo® in August 2017, received a positive ruling in its patent litigation case with AbbVie. A federal court judge ruled that AbbVie, which makes the originator product Humira® must turn over all papers related to the Humira patents. This may actually move the court case out of the discovery phase, according to Fierce Healthcare, and potentially closer to an actual, early biosimilar launch. Third, Health Canada has decided not to add a four-character suffix onto the names of its biosimilars and biologics. Instead, it will rely on its specific drug identification number as well as the nonproprietary names to identify medications being taken. This of course, contrasts with the FDA’s practice. The FDA is the only major advanced regulatory system that requires the use of a suffix to distinguish biosimilars and their reference products. And it is not used by providers.
The multitude of companies that have lined up to sign 2023 licensing
agreements with Abbvie on sales of Humira® biosimilars has grown
again. The latest biosimilar maker added to the list is Coherus Biosciences.
Coherus has an investigational adalimumab biosimilar that completed
a phase 3 trial in 2017 in patients with plaque
psoriasis and psoriatic arthritis. CHS-1420 was found to yield similar
clinical outcomes compared with the reference product.
According to the press
release from Coherus announcing the deal, the biosimilar will be available
for marketing December 15, 2023. This will make it the eighth biosimilar version
of adalimumab to enter the market, with Amgen entering first, in January of
that year. As with the other deals signed by Abbvie, this signing concludes any
patent litigation between the parties and Coherus will pay royalties to Abbvie
on the sales of its biosimilar.
Coherus is expected to file a submission with the European
Medicines Agency, though the timing of this filing has not been disclosed. Furthermore,
it has not yet signed a deal with a marketing partner. In past conference
calls, the biosimilar maker has indicated that it will not focus its resources
on sales of its products outside the US.
COHERUS SUES AMGEN
OVER ADALIMUMAB PATENTS
To complicate matters a bit more, Coherus has launched a patent
infringement suit against Amgen, believed to be the first of a biosimilar
maker against another. Amgen’s Amjevita® was approved by the Food and
Drug Administration in 2016, and has been for sale in the EU. Coherus intends
to file for FDA approval in Q4 2019. Coherus contends that Amgen’s manufacture
of Amjevita violates Coherus’ US patents 10,155,039; 10,159,732; and
10,159,733. These patents involve the creation of stable aqueous formulations of
adalimumab.
Coherus seeks
“damages adequate to compensate for past, present, and future infringement,” which
could have implications for revenues from the European sales of Amgen’s
biosimilar, because of its manufacture in the US. In addition, Coherus seeks an
injunction from the court that permanently enjoins Amgen from engaging in
further alleged infringement.
Coherus President and CEO Denny Lanfear said in its January
25th press release, “Coherus recognized early on the central role intellectual
property would play in advancing biosimilars to market. One important element
of our IP strategy for advancing [CHS-1420] is reflected in the success we’ve
achieved in patenting our innovations in the field of adalimumab formulation.
We believe in the strength of our IP and we intend to protect it.”
Although generic manufacturers engaging in patent suits with
competitors has occasionally occurred, this may be a first in the biosimilar
community. I suppose it was only a matter of time.
On
occasion, we profile some biosimilar manufacturers about whom our readers may
not be familiar. This generally refers to companies that have products that are
in earlier-stage research or those who simply have not been in the news as
often as their colleagues. In this post, we highlight a Guangzhou, China–based company,
Bio-Thera
Solutions.
Established in 2003, Bio-Thera Solutions “is dedicated to
researching and developing innovative and biosimilar therapeutics for the
treatment of cancers, autoimmune, cardiovascular diseases, and other serious
medical conditions.” It claims several biosimilar and innovative therapies in
its pipeline. According to its website, Bio-Thera’s leadership team members
spent extensive time in the US. The CEO and Founder Shengfeng Li was also a
founder of a California company Abmaxis, which was acquired by Merck, and
worked at COR Therapeutics, which became part of Milennium. Chief Medical
Officer Li Zhang worked for eight years at the Food and Drug Administration’s
Center of Drug Evaluation and Research.
Why you may be hearing more about
this company: Bio-Thera
has advanced one of its key molecules, a biosimilar of bevacizumab (reference
product, Avastin®) into a phase 3 study
against EU-licensed Avastin. The company’s objective is to file a 351(k)
application for this product, BAT-1706, with the US FDA and the European
Medicines Agency in 2020.
The company announced a new partnership with Mumbai, India-based Cipla Ltd, to market this product in emerging markets. It is not yet known whether Bio-Thera intends to partner with another organization to market in North America or attempt to build its own sales structure.
Other
products in research and development include an adalimumab biosimilar
(BAT-1406), for which an application for approval has been filed for the
Chinese market, and a phase 1 tocilizumab (Actemra®) biosimilar
(BAT-1806) for the treatment of autoimmune diseases. The company’s information
does not indicate whether either of these products will be targeted for the US market.
In a 2018 press
release, Bio-Thera indicated that biosimilars of secukinumab
(Cosentyx®), golimumab (Simponi®), and ustekinumab (Stelara®)
were also in the pipeline. Regardless of the success of its bevacizumab and
adalimumab biosimilars, the company seems to be well-aligned to address patent
expirations of next-generation biologics.
In other biosimilar news…Regulatory Focus reported Pfizer’s announcement that the drug maker has reevaluated its biosimilar drug pipeline. It has dropped plans to develop 5 biosimilars in preclinical development. The products themselves were not disclosed and were not listed in earlier available version of Pfizer’s drug pipeline. Five other biosimilars in clinical development will continue moving forward, according to the company. This does not affect biosimilars already approved by the FDA. No reason for the decision was given, other than that this was part of an “R&E investment review.”
