At an earnings call this week, Pfizer’s CEO highlighted the
impending launches of Ruxience®
not long after the previously announced launch of Zirabev®
(bevacizumab) at the end of this year.
The New York–based pharmaceutical manufacturer plans to
begin marketing Ruxience in January 2020, and Trazimera February 15, 2020. This
would make Pfizer first to market with a Rituxan® competitor. Pfizer
follows Amgen to market with Trazimera, as Kanjinti®
launched in July this year.
On the call, Albert Bourla, PhD, indicated that the
company’s infliximab biosimilar (Inflectra®) had grown 8% for the
third quarter of 2019 over the same quarter in 2018 (to $77 million). Inflectra’s
marketshare in the US still remains below 10%, according to IQVIA.
Imagine this interesting and perhaps very real-life scenario.
It could have several implications for the present biosimilar marketing
A reference manufacturer, we’ll call them Arby, signs
multiple licensing deals with biosimilar manufacturers, to launch their
products sequentially in 2025. The licensing deals all conclude outstanding
patent litigation between the parties. But one biosimilar manufacturer doesn’t
sign. We’ll call them Brooklyn Industries (BI for short).
Despite Arby’s contention that its patents on the reference
product Yultira are valid until the year 2045, BI decides to launch at risk in July
2020. According to the phased launch schedule, another manufacturer, Thousand
Oaks, was supposed to have the first biosimilar available on the market, with a
three-month jump on the other seven competitors. Does that really give BI a
five-year start over all of its competitors? And what if BI had an
interchangeable biosimilar designation? Would that enable them to lock up the
Deals: The Acceleration Effect
This scenario is actually playing out today with Amgen’s
launch announcement of its trastuzumab and bevacizumab biosimilars (Kanjinti®
and Mvasi®, respectively). Other manufacturers, including Pfizer,
Samsung Bioepis, Mylan/Biocon, Teva/Celltrion have licensing agreements in
place with Genentech (a subsidiary of Roche) for launch of their Herceptin®
biosimilars. Only Amgen’s Mvasi and Pfizer’s Zirabev® are approved (so
far) to compete for the bevacizumab business. The details of the licensing
deals signed by Roche have not been released publicly, so we do not know when
the first “authorized” biosimilars were supposed to launch. Conjecture abounded
that it would be in 2019, nevertheless.
How does Amgen’s Kanjinti launch affect the licensing agreements
that were signed with Roche? Does it mean that Amgen gets a substantial head start
on the competition? Do the licensing contracts consider this possibility?
According to Kevin M. Nelson, JD, at the Chicago-based law firm Schiff Hardin, this scenario is considered in a typical pharmaceutical licensing arrangement. “Typically, settlement agreements in the pharma space include what are called acceleration clauses. Such clauses will allow an agreed-upon launch date to be accelerated to an earlier date in the event the patent or patents are invalidated or found not infringed in another litigation, or if a competing product or authorized competing product comes on the market before that agreed-upon date.”
He added that these acceleration provisions “can come in a variety of flavors from a change in royalty rate or structure, a requirement to leave the market if the ‘unauthorized entrant’ leaves the market, or perhaps agreed damages.”
Accelerating Clauses Are One Thing. Accelerating Launch Is Another Matter
fact that Amgen has announced its immediate launch may present more pragmatic
problems for the other manufacturers, Mr. Nelson pointed out. Let’s say that
you were a member of the Mylan/Biocon team. Your product was approved more than
18 months ago (the first one approved). Let’s also say that your licensing
agreement with Genentech allowed you to launch after November 1 (a purely
speculative, arbitrary date). Finally, assume that your licensing agreement was
generous: it allowed you to launch as soon as possible after another competitor
jumped the starter’s gun. Is it feasible to launch immediately, perhaps four months
“The biosimilar companies cannot just fire up the machines and have product ready tomorrow,” stated Mr. Nelson. There are all of the logistical issues surrounding a launch that must be considered: “Manufacturing, packaging, sales, and distribution all take time,” he said. “And you don’t want inventory to go bad—especially not this type as it is expensive. They may have some reserve lots or made small batches just in case, so we could see a trickle into the market.”
also, that payer and health system contracts are not arrived at overnight. Even
if the Mylan/Biocon team did have lots available for shipment, they might not
have places in the US to ship, other than to a group purchasing organization or
payers will not cover pharmaceutical agents outside of medical exceptions
before the Pharmacy & Therapeutics Committee review, and this can happen anytime
between 60 days and 9 months of the launch. And this is not a product that will
revolutionize therapy or immediately fill an unmet clinical need. Only large
discounts can move the needle here, and establish a contract quickly. Therefore,
the anticipated short window of opportunity that Amgen may have in launching
Kanjinti may get a little shorter but perhaps by not much.
When I mentioned the Arby, er Abbvie, scenario, Mr. Nelson agreed that it would be an entirely different ballgame. Had Boehringer Ingelheim decided to enter the market (as an interchangeable or not), their launch “would have caused absolute chaos.” Imagine trying to pull forward launch date plans of seven manufacturers by three years!
The partnership of Amgen and Allergan made a huge splash in the biosimilar market by announcing the simultaneous US launches of the first two biosimilars of anticancer monoclonal antibodies. The agents Kanjinta® (trastuzumab-anns) and Mvasi® (bevacizumab-awwb) were officially made available July 18.
The move occurred almost simultaneously with a court denial
of Genentech’s request for a restraining
order against Amgen. For Amgen, this marks the first two biosimilars to
The launch discounts associated with these two agents is only 15% off of average wholesale price (AWP), but the manufacturers point out that is still significantly below the average selling price (ASP) of the two reference drugs—13% lower than that for Herceptin® and 12% lower than that for Avastin®. This pricing does not include potential rebates or discounts that could further reduce the net costs of these biosimilars.
The launch timing raises the question of when the
FDA-approved biosimilar competition will be launched. Other biosimilars in the
trastuzumab space have signed
licensing agreements with Genentech, the maker of Herceptin. Their launch
dates have not been disclosed. Several biosimilar makers have also signed
licensing agreements with Genentech on their versions of Avastin, and their
launch dates may be upcoming as well.
Assuming the licensing agreements compel the other
manufacturers to pay some percentage of sales or profits to Genentech, this
could give Amgen/Allergan an automatic edge in profitability. It is unknown
whether the launch timing of Mvasi and Kanjinti, have any implications for the
existing licensing agreements. For example, it may be possible that an early
launch by an unlicensed competitor could negate specific clauses of these
The bevacizumab biosimilar class progress had stagnated
through court proceedings and licensing agreements. In a post from January
2019, we had noted that Amgen had notified the court that it was prepared to
launch as early as
On the trastuzumab side, Amgen/Allergan’s product was the most
recently approved biosimilar (in June 2019).
joint press release, they quoted Paula Schneider, CEO of the Susan G. Komen
Breast Cancer Foundation. “The introduction of biosimilars is an important
step in increasing options for treating HER2-positive breast cancers, which
account for about 25% of all breast cancers,” she said. “As patient
advocates, we are working to ensure that patients are educated about
biosimilars and understand that these FDA-approved treatments are just as
effective as the original biologic drugs.”
And then there was one. Samsung Bioepis and Genentech filed
in District Court to drop all pending patent litigation regarding Ontruzant®,
an approved Herceptin® biosimilar. A Joint Stipulation of Dismissal
is usually the confirmation that a licensing agreement has been reached.
This leaves one
remaining approved trastuzumab biosimilar maker that has not settled with
Genentech (a subsidiary of Roche). Amgen’s product Kanjinti®, which
was the last trastuzumab biosimilar approved (in June), is the last of 5 approved agents
that is not yet subject to a Genentech agreement. The other manufacturers,
Mylan/Biocon, Teva/Celltrion, Pfizer, and now Samsung Bioepis, will likely pay
a royalty to Genentech whenever their products are launched.
Launch dates have not been announced (nor have the terms of
these agreements) for any Herceptin biosimilar. However, the principal patent
for Herceptin® has expired, so biosimilar competition should be available
before the end of the year.
In other biosimilar
Biosciences announced that it has manufactured its 400,000th dose of its
pegfilgrastim biosimilar Udenyca®. Additionally, its unaudited second
quarter earnings seem to indicate positive movement, as much as $84 million (more
than doubling first-quarter earnings of $37 million).