Tag: Sandoz

US Humira Sales Overwhelmed by Biosimilar Competition

Adalimumab biosimilar utilization account for more than 80% of the drug category, as AbbVie’s Humira revenues dry up.

Although the numbers are hard to come by, it seems apparent that adalimumab biosimilar sales have pounded the reference product Humira into submission through the second quarter of 2026. AbbVie announced Humira net revenues of only $425,000,000 for the second quarter, another massive drop of 47% versus the same quarter of last year.

Adalimumab biosimilar sales

The utilization numbers involving biosimilar forms of adalimumab have been complicated by the significant sales of private-label versions through the big 3 PBMs and their subsidiaries. Based on reporting by IQVIA, not all of these private-label prescriptions are reported directly; however, the Pharmaceutical Resources Group recently indicated that the total share of AbbVie’s Humira prescriptions is now below 20%. This roughly aligns with the latest earnings report from AbbVie, showing titanic reductions quarter over quarter. Prior to biosimilar competition in 2023, AbbVie netted $18.6 billion in US sales; it is on track for closer to $1.5 billion through the end of 2026.

As pointed out by Bryce Platt at Drug Channels Institute, and by us in the past, the lowest-price discounting for adalimumab biosimilars has not guaranteed increased preferential coverage for utilization. Instead, private-label contracting by the biosimilar manufacturer seems to move the needle more significantly.

As Skyrizi and Rinvoq Fill the Revenue Gap, Do Health Plans Further Restrict Their Use?

In any case, no one is feeling sorry for AbbVie these days because of the bloated numbers being posted for Skyrizi and Rinvoq sales. These are easily taking up the slack for the hole created by cratering Humira revenues. As a related question, it would be interesting to better understand whether health plans have now firmly decided to require a low-cost adalimumab step prior to covering either Skyrizi or Rinvoq for patients with the dozen or so immunology indications that they are approved to treat.

It’s not a simple question. For example, UnitedHealthcare’s medical coverage policy for Skyrizi in plaque psoriasis requires use of “documentation of moderate-to-severe disease plus failure of at least one conventional systemic therapy (methotrexate, cyclosporine, PUVA, or acitretin) OR prior treatment with any targeted immunomodulator like TNF inhibitors or other biologics.” It also varies by indication: CIGNA’s coverage policy for Skyrizi and Rinvoq in Crohn’s disease and psoriatic arthritis lists it as a preferred step 1 agent, along with adalimumab, Tremfya, Taltz, and ustekinumab biosimilars, whereas Rinvoq is nonpreferred (where patients are directed to adalimumab specifically). This is accompanied by many specific criteria allowing for exceptions to the coverage policy. Then, of course, is the difference between medical coverage and pharmacy coverage policies for these mostly self-administered products.

From a quick scan of these coverage policies, it does appear that the adalimumab and ustekinumab biosimilars have been firmly set as first-step options among biologics. The question of whether their own use require fewer prior authorization criteria (or even no prior authorization scrutiny?) has not been answered. It is extremely important to point out that, as inexpensive as adalimumab biosimilars are today, and as easy as they are to access, these are biologic agents with potentially serious side effects and complications. They are not for every patient, and therefore, prior authorization criteria should probably remain in place, even as they grow in utilization and remain inexpensive.

In Other Biosimilar News

According to an agreement between Sandoz and Shanghai Henlius, Sandoz will have global commercialization rights (outside of China) to up to 10 potential biosimilar candidates being developed by Henlius, including three announced agents: evolocumab (reference product, Repatha) for the treatment of hypercholesterolemia, belimumab (Benlysta) for the treatment of systemic lupus, and cetuximab (Erbitux) for the treatment of colorectal cancer.  

This article was written by our Director of Content, Stanton Mehr. Stan has been writing commentary and reporting news about the biosimilar industry since the submission of the first biosimilar 351(k) application to the FDA 13 years ago. Since that time, BR&R has been tracking the US biosimilar marketplace, with the industry’s original, comprehensive and updated database of biosimilar filings with the FDA. 

Senate Bill on Patents Could Turn the Purple Book Into Something More Useful

The Biologic Patent Transparency Act (BPTA), a Senate bill introduced by Senator Susan Collins (R-ME) in March, is an independent, bipartisan attempt to address patent thickets. It does so largely by clarifying an individual biologic product’s patent situation. In achieving this, it can also create a real reason for the existence of the Purple Book.

Biologic Patent Transparency Act

Today, the Purple Book is nothing more than a listing of biologic agents, their original FDA filing dates, and whether there are any biosimilars of the originator biologic. It provides very few dates when a biologic’s exclusivity period ends. One day, it may list whether a biosimilar is interchangeable with a reference drug, but there are no designated interchangeable biosimilars today (and that seems to be the case in the near future, at least).

Under the Senate BPTA proposal, the originator manufacturer must disclose all relevant patents to the Secretary of Health and Human Services. It states that “…a ‘patent required to be disclosed’ is any patent for which the holder of a biological product license approved under subsection [351](a) or (k), or a biological product application approved under section 505 of the Federal Food, Drug, and Cosmetic Act and deemed to be a license for a biological product under this section on March 23, 2020, believes a claim of patent infringement could reasonably be asserted by the holder, or by a patent owner that has granted an exclusive license to the holder with respect to the biological product that is the subject of such license…” We assume that the patent lists will be provided via the Purple Book, which is supposed to be a reference for prospective biosimilar manufacturers.

The BPTA strives to make the patents held by a manufacturer as transparent as possible. It would require drug makers to list exclusivity periods or any exclusivity extensions received, information related to interchangeability or biosimilarity of a product, approved indications, and mandates updates every 30 days. Of course, this language does not prohibit, restrict, or redress any existing patents. Any changes in the patent law is not the addressed in this proposal.

The seven bill cosponsors (as of May 2, 2019) include a group as diverse as Tim Kaine (D-VA) to Rand Paul (R-KY).

In other biosimilar news…Sandoz announced a partnership with Taiwan-based EirGenix to commercialize the latter’s investigational trastuzumab biosimilar. This agent is currently in phase III trials. Under terms of the agreement, Sandoz will market the agent globally, except for China and Taiwan.

Second Etanercept Biosimilar Receives FDA Approval

Samsung Bioepis scored another biosimilar approval in the US, as the Food and Drug Administration gave its nod to etanercept-ykro on April 25, 2019. Formerly known as SB4, Samsung Bioepis dubbed this agent Eticovo™. It is the second
Enbrel® biosimilar to to receive US approval.
 
This approval covered all of the reference product’s autoimmune indications, including ankylosing spondylitis, polyarticular juvenile idiopathic arthritis, psoriatic arthritis, plaque psoriasis, and rheumatoid arthritis. Clinical studies were performed in patients with moderate-to-severe rheumatoid arthritis, finding that in combination with methotrexate, Eticovo achieved ACR20 scores that were equivalent to that of Enbrel by week 24 (78.1% vs. 80.3%, respectively). Safety and immunogenicity were also comparable with those of the reference agent.

Eticovo has been approved in the EU and Canada, in addition to other parts of the world, under the brand names Benepali and Brenzys. Samsung Bioepis has not announced a launch date in the US for its biosimilar, and this can be delayed for quite some time. Sandoz’s Erelzi® was approved in 2016, but has not yet reached the market because of patent litigation. Amgen, which manufacturers Enbrel, believes its patents extend effectively into 2028, which would provide for nearly 30 years of product exclusivity.


Both Coherus and Lupin have investigational etanercept biosimilars that are in phase 3 trials. Neither has publicly filed for FDA approval to date.

Sandoz Resubmits Its Pegfilgrastim Biosimilar Application

Sandoz may be chomping at the bit to market its long-delayed pegfilgrastim biosimilar. First rejected by the Food and Drug Administration (FDA) in 2016, the manufacturer of Zarxio® (filgrastim) has completed its 351(k) biosimilar resubmission for its pegylated filgrastim agent.

The FDA’s complete response letter to Sandoz required new pharmacokinetic and pharmacodynamics data, which Sandoz has provided. According to Sandoz’s press release, “The resubmission includes new data from a pivotal pharmacokinetics (PK) and pharmacodynamics (PD) study. This was a single-dose, three-period cross-over study comparing Sandoz pegfilgrastim with US-sourced reference pegfilgrastim; Sandoz pegfilgrastim with EU-sourced reference pegfilgrastim; and US with EU-sourced reference pegfilgrastim.” Branded Ziextenzo™, this agent was approved in Europe and launched in November 2018.

Sandoz was hoping that its pegfilgrastim biosimilar would be first to market before its 2016 set back. Several other prospective pegfilgrastim biosimilar makers also received rejections from the FDA, including Mylan/Biocon’s Fulphila® and Coherus Biosciences’ Udenyca®, both of which are now marketed. If approved, Sandoz would be (at best) third to market. However, of the competitors, Sandoz is the only manufacturer that can boast both a filgrastim and pegfilgrastim biosimilar. Of course, Amgen produces both Neupogen® and Neulasta®, the respective reference products.

A FDA decision date has not yet been announced; a decision in the late third quarter of 2019 would be a reasonable expectation.

Besides Zarxio, Sandoz already has received approval for two other biosimilars (Hyrimoz®, a biosimilar of trastuzumab, and Erelzi®, a biosimliar of etanercept, but these two have not yet been launched because of outstanding patent litigation or settlements. Despite having received approval in the EU for its biosimilar of Rituxan®, Sandoz decided not to press for US approval after receiving a complete response letter from the FDA about a year ago.

Coauthor of Hatch–Waxman Act Attacks the Use of IPR Process for Biosimilars

The Hatch–Waxman Act (officially, The Drug Price Competition and Patent Term Restoration Act of 1984) enabled generic medications to be marketed after branded patent expirations. One of the bill’s cosponsor, Senator Orrin Hatch (R-UT), is now spurring a legislative proposal that would protect reference drug manufacturers from use of the inter partes review (IPR) system. This action would result in further delayed access to lower-cost generics and biologic medicines.

Inter partes review is used by makers of generic drugs and biosimilars to challenge weaker patents. It enables the parties to bypass lengthier litigation through the courts, potentially helping less-expensive drugs reach the market faster than otherwise possible.

Hatch-Waxman Act
Senator Orrin Hatch (R-UT)

Called the Hatch–Waxman Integrity Act, this amendment to the CREATES Act was introduced December 11, 2018 simultaneously into the Senate and the House (by Representative Bill Flores, R-TX). If passed this amendment could significantly limit the ability of generic and biosimilar manufacturers to use the IPR process to speed patent review and litigation.

Seemingly a contradictory stance by Senator Hatch, he believes that the IPR process may too strongly affect the balance between access to medications and biopharmaceutical innovation.

In any case, this proposal would have a very difficult road to passage. First the administration’s current efforts to make biosimilars available as soon as possible runs counter to this bill. Second, the shift to the Democratic majority in the House could be an insurmountable barrier to passage.

In other biosimilars news…Sandoz seems to be entering the biosimilar insulin marketplace, with its agreement to commercialize three different types (insulin aspart, glargine, and lispro) that will be manufactured by the Chinese company Gan & Lee. Sandoz will be responsible for the US and Canada, the EU and Switzerland, Australia and New Zealand, and Japan. In the US, insulin makers can file applications for biosimilar status as of 2020.

Additionally, Pfizer received good news from Europe, receiving a positive recommendation from the EMA’s Committee for Medicinal Products for Human Use (CHMP) on its bevacizumab biosimilar Zirabev (reference product, Avastin®).

Rituximab Biosimilar Approved by FDA for Cancer Treatment

On November 28, 2018, the Food and Drug Administration (FDA) announced the approval of rituximab-abbs (Truxima™), produced by Celltrion and marketed by Teva.

Approval for this rituximab biosimilar was overwhelmingly recommended by the FDA’s Oncology Drug Advisory Committee by a vote of 16-0 in October. It is the first biosimilar agent approved for the treatment of relapsed or refractory, low grade, or follicular non-Hodgkin’s lymphoma—specifically in adult patients with the CD20+ B-cell variety. The drug makers did not seek approval for the Rituxan’s autoimmune indications, and the FDA did not grant extrapolated approval for them.

rituximab biosimilarAccording to the FDA’s announcement, the most common side effects of Truxima are infusion reactions, fever, abnormally low level of lymphocytes in the blood (lymphopenia), chills, infection and weakness (asthenia). Health care providers are advised to monitor patients for tumor lysis syndrome (a complication of treatment where tumor cells are killed off at the same time and released into the bloodstream), cardiac adverse reactions, damage to kidneys (renal toxicity), and bowel obstruction and perforation.

This leaves a wide open marketing window for Celltrion and Teva, as Sandoz announced in late October that it was halting its effort to bring its own rituximab biosimilar to the market. There is no word as of this writing regarding the launch and pricing of Truxima in the US. This also represents the second FDA approval for Celltrion; its infliximab biosimilar, Inflectra, was approved in 2016.

In Other Biosimilar News… As BR&R reported in our October discussion with Molly Burich, MS, Director, Public Policy: Biosimilars and Pipeline, Boehringer Ingelheim had decided to forego marketing its adalimumab biosimilar Cyltezo® in the EU. This is likely owing to the highly competitive environment and the huge pricing discounts being signed by European countries. However, Boehringer has now announced its intention to discontinue all efforts to market and develop any biosimilars outside of the US market. This may come as little surprise, as the Boehringer biosimilar pipeline was not aggressively stocked. Instead, it has been focused on seeking interchangeability status for Cyltezo and to launch this product as soon as possible.

United Kingdom to Save 75% on Annual Humira Spending

Since the October expiration of Abbvie’s EU patent, the potential Humira savings seem to be truly mind-blowing. After implementing its contracts for adalimumab, the UK National Health Service (NHS) should save about three quarters of the $514 million (£400 million) it spends each year on this product alone.

In a fixed-budgeted system like that in the UK, the real implications of these savings become clear. According to the NHS, this additional $385 million (£300 million) will enable it to pay for 11,700 community care nurses or 19,800 treatments in patients with breast cancer.

And to earn these Humira SavingsHumira savings, the NHS does not exclude using the originator product Humira. It has signed contracts (with large price cuts) with Abbvie, as well as with biosimilar manufacturers Amgen, Biogen, Mylan and its partner Fujifilm Kyowa Kirin, and Sandoz.

Could the US see such savings on adalimumab in 5 years? Although the competition may be fierce when the brand loses patent protection in 2023, Abbvie has created a stepped-launch scenario with its licensing agreements. Rather than a jailbreak of competition, as we are seeing in the EU with patent expiration there in October 2018, the timing of the licensing agreements may limit the drop in per-unit price, at least for the first year or so.

After that time, payers will be able to choose from all biosimilar adalimumab manufacturers, which should then drive pricing down (or rebates up) considerably, resulting in long-sought lower net costs. However, this will happen only after years of price increases by Abbvie. Abbvie has not claimed, while it is drastically slashing its price in the EU, that it will be losing money. In part, that is because its US revenues on Humira will continue to be at over $10 billion a year. Furthermore, its revenues largely reflect pure profit on the manufacturing of the product today, as its research and development costs were covered 15 years ago and ongoing marketing costs are a tiny fraction of this figure.

Despite repeated protestations in the US that healthcare resources are not unlimited, our system is not based on a fixed budget. It is not disingenuous to consider savings in the terms posed by NHS. Defining the large savings in terms of other useful expenditures give people a concrete idea of how the money can be better used. The need for savings on drug expenditures is acute in this nation, and biosimilars will eventually lead the way.

Momenta Signs Licensing Deal With Abbvie. Did It Have a Choice?

We previously reported that Momenta Pharmaceuticals reevaluated its biopharmaceutical strategy going forward, deciding to move forward only with its investigational adalimumab and aflibercept biosimilars. Yesterday, Momenta announced that it has joined the long queue of pharmaceutical manufacturers signing a biosimilar licensing deal with Abbvie, which will allow commercialization of M923, its biosimilar to Humira, should it obtain regulatory approval. Momenta’s licensing deal is the fifth one signed by prospective biosimilar marketers in the US.

This agreement was pretty much a no-brainer for Momenta. The company did not have the stomach for attempting either an extended patent fight or an at-risk launch. However, the biosimilar licensing agreement only allows Momenta to market its adalimumab biosimilar in the US after December 2023, which will make it the fifth Humira biosimilar that will launch under the licensing agreements (Table). The main patents for Humira have expired in Europe, and these agreements have generally allowed the European launches to occur as of October 16 of this year.

Of the manufacturers signing biosimilar licensing deals with Abbvie , only Amgen and Sandoz have earned FDA approval for Amjevita® and Hyrimoz®, respectively. And Boehringer Ingelheim is still duking out patent litigation with Abbvie in the courts over its approved biosimilar agent Cytelzo®, for which it hopes to receive an interchangeability designation. The second through fifth agents entering the fight will be likely pounding away at subsequently smaller slices of revenue.

Perhaps the most frustrating part is that Abbvie is running a lucrative game; it will collect royalties from all of these manufacturers in 2023 and beyond, which will help offset declining marketshare from its biggest revenue contributor.

 

In Abbvie’s Web: Who Has Signed Licensing Agreements for Biosimilar Adalimumab?

Company/Partner

Drug Name

Launch Date

Amgen

Amjevita*

January 2023

Samsung Bioepis/Merck

SB5

June 2023

Mylan/Fujifilm Kyowa Kirin Biologics

Hulio

August 2023

Sandoz

Hyrimoz*

September 2023

Momenta

M923

December 2023
*Received FDA Approval.

Note: This post was revised and corrected, November 8, 2018.

Sandoz Decides Against Marketing Rituximab Biosimilar in US

On October 30, Novartis announced that it was culling its investigational drug pipeline and dropping 20% of its development programs. Just three days later, its subsidiary Sandoz announced that it would halt its efforts to obtain approval for its biosimilar version of rituximab from the US Food and Drug Administration (FDA). The decision by Sandoz to halt its rituximab biosimilar filing efforts seems to have culminated from Novartis’ announcement and FDA actions.

Sandoz had received a complete response letter on May 2, 2018 in its attempt to obtain approval for use for Rituxan®’s oncologic (but not autoimmune) indications. According to Sandoz’s press releaSandoz Halts Rituximab Biosimilar Filingse, the FDA had asked them for additional information before providing a new decision. Sandoz did not specify the type of data sought in the request, although the company’s Global Head of Biopharmaceuticals, Stefan Hedriks, hinted that additional studies were involved. He stated, “We appreciate the important conversations with the FDA, which have provided specific requirements for our potential US biosimilar rituximab, but believe the patient and marketplace needs in the US will be satisfied before we can generate the data required.” Generally, that means more than a re-analysis of existing data. This seems to be the principal reason for its decision to development and the rituximab biosimilar filing.

However, Rituxan is already available in several major markets, including Australia and New Zealand, the European Union, Japan, and Switzerland. Sandoz received US approval for three biosimilars, but only Zarxio® is currently marketed. Next up for Sandoz will be a refiling for FDA approval of its pegfilgrastim biosimilar. The company announced the original FDA rejection of this product in July 2016.

A Third Biosimilar Adalimumab Approval in the US and Potentially Huge Humira Price Discount in Europe

The Food and Drug Administration (FDA) announced yesterday the approval of adalimumab-adaz from Sandoz. The new agent, dubbed Hyrimoz™, will not be launched in the US until 2023. The approval of Hyrimoz is the third for Sandoz (but only one, Zarxio®, is available for prescription in the US).

The FDA approval of adalimumab-adaz covered several indications, including adult Crohn’s disease, ankylosing spondylitis, juvenile idiopathic arthritis, plaque psoriasis, psoriatic arthritis, rheumatoid arthritis, and ulcerative colitis. The drug’s approval was based partly on the findings of a phase 3 clinical trial in patients with chronic plaque psoriasis, in which the biosimilar was found to be noninferior to the originator product Humira® in terms of efficacy (i.e., PASI 75 score) and safety.

Hyrimoz is the third  approved adalimumab biosimilar, none of which have been marketed due to patent litigation.  Abbvie has signed licensing agreements with Amgen and Samsung Bioepis to delay US launches.

HUMIRA PRICE DISCOUNT IN THE EU

This biosimilar is being marketed in the EU, competing with several others for the Humira marketshare overseas. However, signs of real competition are heating up in Europe, as Abbvie has offered a Humira price discount of as much as 80%.

According to an article published in Fierce Pharma, Abbvie is hoping to squash the biosimilar competition and prevent it from gaining valuable European experience ahead of US launches in 2023. The article cited a report by Bernstein analyst Ronny Gal, indicating that even at an 80% discount, Humira will still be profitable for Abbvie. “The objective is to defend the US market by denying the biosimilars in-market experience [in Europe] and then arguing the Europeans ‘chose’ Humira over the biosimilars for quality reasons beyond price,” according to Gal’s report.

On the other hand, this puts the biosimilar makers in a tight spot on the continent. They need to earn back their R&D costs and may be unwilling to face an immediate low-profit reality. Revenues within the EU for Humira are $4 billion. Even if it offered tenders of 80% for every member country (and they were accepted), revenues would still be in the range of $800 million. This would drastically reduce the size of the revenue slices for the European biosimilar competitors. It could be possible that some may drop out of the market, at least until the time of the US launches.