In the next 10 years, the two "pharmaceutical kings" will carry 15 blockbuster drugs with successive patents that expire, and the opportunity for $110 billion in imitations is here

AbbVie's Humira patent protection in the United States will expire in 2023

Since AbbVie signed the first Humira biosimilar settlement agreement with Amgen in September 2017, AbbVie has signed eight similar Humira biosimilar settlement agreements, including Boehringer Ingelheim, Pfizer, Samsung Bioepis, Mylan, Sandoz and other companies have extended Humira's patent protection in the United States

However, not every biosimilar developer is willing to settle with AbbVie

As the industry's highest-selling drug, Humira has attracted a lot of attention over the years-but not all are positive

AbbVie has been preparing for the Humira patent cliff for many years, and the upcoming biosimilar competition is the driving force behind the company's decision to acquire Allergan for $63 billion in 2019

Although there is competition for biosimilars in Europe and other regions, Humira generated US$19.

2.

Keytruda was first approved by the FDA in 2014 and is still on a rapid growth track

At the same time, Keytruda's wide range of indications have become the driving force for its sales growth, including metastatic non-small cell lung cancer (established as the standard of treatment for newly diagnosed patients), as well as kidney cancer, postoperative melanoma and bladder cancer

The expanded list of Keytruda indications will only get longer

In its annual evaluation report released in December last year, Evaluate Pharma predicted that as the undoubted king of PD-1/L1 inhibitors, Keytruda is expected to replace AbbVie's Humira in 2023 and become the world's best-selling drug

On the other hand, Keytruda is becoming more and more successful, and Merck needs to prepare for the drug before the patent cliff in 2028

Some of Merck’s internal R&D programs can help compensate for the invasion of biosimilar drugs
.
This includes the 15-valent pneumococcal vaccine V114, which is comparable to Pfizer's blockbuster Prevnar 13 and its newly approved follow-up injection Prevnar 20
.
Merck’s P2X3 receptor antagonist Gefapixant for the treatment of chronic cough is currently under review by the FDA and has the potential for wider indications
.

But these drugs are not enough to fill Keytruda's revenue, so Merck is also looking for business development opportunities externally
.

Merck has just raised $9 billion in cash by splitting its women’s health, biosimilar drugs and mature drugs into Organon, and is ready to buy
.

The company has just acquired Pandion Therapeutics for approximately US$1.
9 billion and obtained an IL-2 drug for the potential treatment of autoimmune diseases
.
Merck also recently spent US$2.
75 billion to acquire VelosBio to develop potential first-class ROR1 anticancer drug conjugates
.

3.
Revlimid (lenalimid)

Revlimid was acquired by Bristol-Myers Squibb when it acquired New Foundation for US$74 billion in early 2019
.
Revlimid is used to treat multiple myeloma, myelodysplastic syndromes and other diseases.
It will perform well in 2020, with sales of approximately US$12.
15 billion
.
However, the drug eclipsed AbbVie's immunology giant Humira and Merck's immuno-oncology drug Keytruda, and the drug's generic competitors will join the competition between 2025 and 2026
.

However, before Bristol-Myers Squibb/Xinji reached a settlement agreement with four generic drug companies (Natco, Alvogen, Dr.
Reddy Laboratories and Sun Pharmaceuticals), it may launch a limited number of Revlimid generic drugs as early as March 2022
.
The agreement will end on January 31, 2026, when these companies are free to sell "unlimited" generic drugs
.

At the same time, Revlimid's 2020 success can be attributed at least in part to rising prices
.
The drug was approved for the first time in 2005 and was launched by Xinji at a price of US$215 per capsule
.
U.
S.
Congressional investigators said in September that in the following years, more than 20 price hikes caused the price of each grain to soar above $750
.
The investigation pointed out that Xinji formulated these price increase plans to achieve its financial goals
.

4.
Elito/Eliquis (Apixaban)

Bristol-Myers Squibb and Pfizer’s blockbuster drug Eliquis had sales of US$9.
17 billion last year, an increase of 16% over 2019, and has a place in the top five best-selling drugs in the world in 2020
.

The Eliquis generic drug has received provisional approval from the FDA
.
However, due to last year’s settlement and key litigation, it will be able to withstand generic competitors at least until 2026
.

Two companies, Bristol-Myers Squibb and Pfizer, have been working hard against generic competitors for many years
.
For example, in 2017, Bristol-Myers Squibb and Pfizer filed patent infringement lawsuits against 25 companies that have applied to the FDA for approval of their generic drugs
.

In August of the same year, the U.
S.
Patent and Trademark Office granted Eliquis a key substance component patent, extending its patent protection from February 2023 to November 2026
.
The drug also has another formula patent, which is valid until 2031
.

The two companies eventually reached a legal settlement with several of their competitors, including Mylan (now Viatris) and Micro Labs
.

However, not all competitors will give in
.

Then in August of that year, when a Delaware District Court judge upheld Eliquis' patent against other generic challenges from Sigmapharm, Sunshine Lake and Unichem, Bristol-Myers Squibb and Pfizer achieved another major victory
.
Unless an appeal or future challenge produces any new results, ensure that Eliquis continues to monopolize the market for several years
.

For Bristol-Myers Squibb, the company is facing the three biggest patent cliffs in the next decade for Eliquis and cancer drugs Revlimid and Opdivo
.
The imminent invasion of generic drugs caused the company to acquire New Base for US$74 billion and MyoKardia, which was acquired for US$13.
1 billion, and set off a frenzy of mergers and acquisitions
.

5.
Eylea (Eylea)

Regeneron’s best-selling drug Eylea was approved for the treatment of wet age-related macular degeneration, diabetic retinopathy, and diabetic and non-diabetic macular edema.
Last year's sales were 8.
36 billion U.
S.
dollars, an increase of 7% over 2019
.

Eylea has already competed with Novartis’ Beovu, but the biggest threat to Eylea may be that its key patents expire in 2025-2026
.
The main competitors come from Novartis’ generic drug companies Sandoz, Amgen, and Samsung Bioepis
.

Sandoz said in May that it will soon begin registration of its Eylea biosimilar drug Phase III Mylight study
.

At the same time, South Korea's Samsung Bioepis began late-stage research on its Eylea biosimilar SB15 at the end of June last year, and the trial is expected to end in April next year
.
Other South Korean biosimilar companies, Alteogen, Celltrion, and Samchundang Pharm are also developing generic versions of this product
.

In the United States, the pharmaceutical giant Amgen is expected to complete its own Phase III trial of Eylea biosimilar drug in April 2022
.

Another potential threat is the emergence of biosimilars of Roche's wet age-related macular degeneration drug Lucentis, which may face competition from biosimilars in the second half of this year
.
In November last year, the FDA stated that it would review the applications of Samsung Bioepis and Biogen's Lucentis biosimilar SB11, which will undergo a standard 12-month review
.
If Lucentis biosimilars are launched in the second half of 2021, it may swallow a large portion of Eylea's market share at a low price
.

6.
Starno/Stelara (Usnumab)

Johnson & Johnson's best-selling immune drug Stelara is used to treat plaque psoriasis, psoriatic arthritis and Crohn's disease.
Last year's revenue was $7.
7 billion, an increase of 21% over 2019
.
The key patent for the drug expires between 2025 and 2026
.

However, Johnson & Johnson stated in its annual filing to the US Securities and Exchange Commission in 2020 that the last patent for the drug will expire in 2023
.

Many biosimilar manufacturers are potential competitors for Stelara
.
South Korea’s Celltrion seems to be the fastest in the competition, and its drug candidate is already in phase III testing for Stelara
.
The study should end in the second half of 2022, so if it succeeds, the company may be preparing to launch it in 2023 or 2024
.

In addition, several other biosimilar manufacturers, including Bio-Thera Solutions, Epirus Biopharmaceuticals and NeuClone, are conducting early testing of their potential generic versions of Stelara
.

With the imminent arrival of biosimilar drugs, Johnson & Johnson will seek to increase sales of other immunological drugs
.
Tremfya, another immune product of Johnson & Johnson, is gaining rapid growth in the psoriasis market
.

7, Odivo/Opdivo (Navulimab)

In terms of sales, Bristol-Myers Squibb’s Opdivo is far from its rival Merck’s Keytruda, but its sales of $7 billion in 2020 should not be underestimated
.
The drug was down 3% year-on-year
.
Company executives attributed it to the new crown pneumonia pandemic and repeatedly stated that the drug will resume growth this year
.

Some new indications may drive Opdivo's growth
.
As the world's first approved PD-1 inhibitor, it entered the lucrative new diagnostic metastatic non-small lung cancer market last year
.

Opdivo is also ahead of Keytruda in gastric cancer
.
The drug was approved by the FDA in April for use in previously untreated gastric cancer, gastroesophageal junction cancer and esophageal adenocarcinoma
.
In May of this year, Opdivo became the first cancer immunotherapy approved as a postoperative adjuvant treatment for cancer of the esophagus or gastroesophageal junction
.
The use before and after surgery is considered to be a huge growth opportunity for PD-1/L1 blockers
.

Bristol-Myers Squibb also hopes to enhance Opdivo's position through new drug combinations, including a combination with a new checkpoint inhibitor LAG-3 antibody relatlimab for first-line metastatic melanoma.
Research shows that it is superior to Opdivo alone.

.

Evaluate Pharma predicted in a report that by 2026, Opdivo's global sales may reach 11.
75 billion U.
S.
dollars
.
According to securities documents recently submitted by Bristol-Myers Squibb, Opdivo will lose its exclusivity in the US market in 2028
.
Pharmaceutical companies developing Opdivo biosimilars include Sydney company NeuClone Pharmaceuticals, Swedish company Xbrane Biopharma and China Luye Pharma
.

8.
Dolutegravir (Dolutegravir)

GlaxoSmithKline’s dolutegravir has been the main product of its HIV drug portfolio under its joint venture ViiV Healthcare
.
But with a key patent expiring in 2028, the company is now betting on long-acting injections
.

Dolutegravir is one of GSK's four best-selling HIV brands-Tivicay, Triumeq, Juluca and Dovato
.
All in all, products containing dolutegravir will harvest $6 billion in 2020, accounting for more than a quarter of GlaxoSmithKline’s total sales
.

After dolutegravir's patent expires in 2027, these drugs will have to withstand the pressure of generic drugs
.
There are two patents protecting dolutegravir, one is that its molecule will expire in 2027, and the other is that its crystal form will expire in 2029
.

According to the annual report of GlaxoSmithKline, in 2017, the crystal form patent faced challenges from generic drug giants such as Mylan, Cipla, Sandoz, and Dr.
Reddy's laboratories.
These companies claimed that the patent was invalid and the patents they developed The product is not infringing
.
GlaxoSmithKline has reached an agreement with Dr.
Mylan and Reddy, who are now taken over by Viatris
.
At the same time, the company has filed patent infringement lawsuits against other defendants, including Cipla, Apotex, Rubin and Sandoz.
The date of the verdict has not yet been determined
.

By 2031, ViiV expects that 90% of its HIV business will come from long-acting therapies
.

After setbacks in 2019, the company's monthly HIV injection Cabenuva finally received FDA approval
.
Cabenuva combines ViiV's cabotegravir and Johnson & Johnson's rilpivirine
.

The goal of ViiV is to develop injections that are administered for a longer period of time, such as the frequency of dosing every two months
.

ViiV recently partnered with Halozyme, a biotechnology company based in San Diego, California, to try to further extend its dosing interval, possibly from every two months to three to six months
.

The company is facing competition from two heavyweight companies: Gilead and Merck, which announced in March that it plans to combine its antiviral drugs-Gilead's lenacapavir and Merck's islatravir-to develop a weekly oral drug.
And an injection every three months
.

9.
Ibrance/Ibrance (Pepicili)

The breast cancer drug Ibrance has been a key blockbuster for Pfizer for many years
.
Pfizer predicts that the drug will not lose its exclusive rights in the United States before 2027, but this has not prevented generic drug manufacturers from formulating development plans for their generic drugs
.

As early as 2019, a number of generic drug manufacturers notified Pfizer that they had applied for generic drug approval and considered that the two key patents of the drug were invalid
.
A recently controversial patent will be extended for four years to 2027, and the drug's crystal form patent will expire in 2034, which also faces challenges
.

Pfizer stated in a recent securities filing that in response, Pfizer has sued generic drug companies in various federal courts
.
These include two lawsuits against Aurobindo Pharma and Dr.
Reddy
.

As a major asset in Pfizer's oncology product portfolio and a growth driver for the entire company, Ibrance is an important brand that Pfizer aims to protect
.
The drug's sales in 2020 were 5.
39 billion U.
S.
dollars, a year-on-year increase of 9%
.

However, the drug has recently come under pressure from rivals Novartis Kisqali and Eli Lilly and Company Verzenio
.
Ibrance’s sales fell by 7% in the first quarter of 2021, but Pfizer attributed the decline to an increase in the number of enrollments in the drug’s patient assistance program, as patients suffered financial difficulties related to the new coronary pneumonia
.
Pfizer CEO Albert Bourla said on a conference call in May that the drug is still the clear leader in the CDK category, accounting for 84% of first-line drug use
.

In the company's oncology field layout, the revenue of the prostate cancer drug Xtandi, which is cooperating with Astellas, has been growing, and the PD-L1 inhibitor Bavencio, which cooperating with Merck, has been adding new indications
.
In addition to these products already on the market, the company's late pipeline looks weak
.

To strengthen its oncology product portfolio, Pfizer acquired cancer drug development company ArrayBioPharma for US$11.
4 billion in 2019
.

10.
Genovia/Januvia (sitagliptin) and Genova/Janumet (sitagliptin/metformin)

Last year, Merck’s blockbuster type 2 diabetes drug Januvia and its compound product Janumet earned US$5.
3 billion in revenue worldwide
.
But with sales falling by 7% in 2019 and 4% last year, patent protection will soon be lost in January 2023
.

Over the years, Merck has spared no effort to protect its Januvia and Janumet patents, and has engaged in long-term court battles with various generic drug manufacturers, including Mylan and Par Pharmaceuticals
.

But most of Merck's lawsuits against Januvia were conducted in India
.
Last year, Merck and Accord Healthcare reached a settlement to stop the development of generic drugs in Januvia
.
Merck said in its 2020 annual report that this is one of nine settlements with generic drug manufacturers on Januvia
.

As disclosed in its 2020 annual report, Merck still hopes to expand its exclusive rights to Januvia through another patent covering "certain phosphates and sitagliptin polymorphs
.
" Par Pharmaceutical questioned the validity of the patent, which will not expire until 2027
.
The protection period of Janumet's salt and polymorphic formulations is 2029
.

The loss of the Januvia/Janumet franchise will have a significant impact on Merck
.
Merck had to do its utmost to achieve its much-needed diversification, such as the acquisition of Oncolmmune and Themis, which were aimed at developing epidemic drugs, but were unsuccessful
.

In addition, Eli Lilly, Amgen, Novartis, Takeda, and Novo Nordisk all have products with sales of more than $3 billion in 2020 and their patents expire in the next ten years
.

The overall sales of the 15 drugs in 2020 reached 115.
92 billion U.
S.
dollars
.

It is worth mentioning that some drugs have lost patent protection in China, and some generic drugs have been approved for marketing
.