The "patent cliff" crisis of the world's top four best-selling drugs is approaching. How do AbbVie, Merck and BMS respond?

Humira:

Where is the successor of the global "pharmaceutical king"?

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

In fact, AbbVie has also made preparations for many years to deal with Humira's "patent cliff", successfully preventing the listing of biosimilar drugs in the United States through patent strategies, negotiations, and litigation
.

The competition of biosimilar drugs will eventually come.

Skyrizi is an IL-23 p19 monoclonal antibody developed by AbbVie.

In 2019, Rinvoq was approved for listing for the first time.
With only one indication for rheumatoid arthritis, its sales surged from US$47 million to US$730 million last year
.

In China, adalimumab was approved for the first time in 2010
.

  After the official launch of adalimumab injection, Biotech also broke the zero-revenue status.
In 2020, it recorded a total of 183 million yuan in revenue from the sales of Gelly
.

Keytruda:

Expected to reach the top of Merck & Co in 2023, need to plan ahead

  Keytruda, Merck’s PD-1 king, will lose its exclusivity in the US market in 2028
.

  Evaluate Pharma predicted in a report released in December last year 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
.
The drug's global sales by 2026 may reach 24.
32 billion U.
S.
dollars
.
  

  On the other hand, Keytruda is becoming more and more successful, and Merck needs to prepare for the drug before the arrival of the "patent cliff" in 2028
.
In fact, biosimilars are already brewing: A Canadian company called PlantForm Corporation recently announced a collaboration with Bio-Manguinhos/Fiocruz of the Brazilian Ministry of Health to develop Keytruda biosimilars for the Brazilian market
.
Sydney-based NeuClone Pharmaceuticals and the Serum Institute of India are also collaborating on projects including Keytruda biosimilars
.
  

  Merck's related products on the R&D line may help meet the challenges of biosimilar drugs to a certain extent
.
These include the 15-valent pneumococcal vaccine V114, which is comparable to Pfizer's blockbuster Prevnar 13 and the newly approved Prevnar 20
.
The P2X3 receptor antagonist Gefapixant for the treatment of chronic cough is currently being reviewed by the FDA, and the drug also has the potential to be used in a wider range of indications
.
  

  But these drugs are not enough to fill Keytruda's future revenue gap, so Merck is also looking for business development opportunities externally
.
The company just raised $9 billion in cash by splitting its women’s health, biosimilar drugs and mature drugs into Organon, and is ready to buy
.
  

  Earlier this year, Merck acquired Pandion Therapeutics for approximately US$1.
9 billion and obtained an IL-2 drug for the potential treatment of autoimmune diseases
.
It also spent US$2.
75 billion to acquire VelosBio to develop potential first-class ROR1 anticancer drug conjugates
.
    

Revlimid &  Eliquis:

BMS is under great pressure or open "buy, buy, buy"

  For Bristol-Myers Squibb (BMS), not only Revlimid and Eliquis, but Opdivo will also lose patent protection in the United States in the next 10 years
.
As blockbuster products continue to usher in the "patent cliff", it is expected that BMS will become one of the most active M&A traders in the next few years
.
  

  Revlimid was acquired by BMS when it acquired New Foundation for US$74 billion in early 2019
.
At that time, the future of the drug was still full of uncertainties due to patent issues.
It was only after a series of settlements with generic drug manufacturers and a big victory in the US patent litigation that some of the uncertainties were eliminated
.
  

  In September 2020, BMS reached a settlement agreement with four generic drug companies (Natco, Alvogen, Dr.
Reddy Laboratories, and Sun Pharmaceuticals)
.
A limited number of Revlimid generic drugs may be launched as early as March 2022 .
The agreement will end on January 31, 2026, when these companies are free to sell "unlimited" generic drugs
.
  

  In China, in January 2013, lenalidomide capsules were approved for marketing
.
In 2020, Beijing Shuanglu Pharmaceutical's Lenalidomide Capsules passed the consistency evaluation, becoming the third domestic company to be evaluated after Chia Tai Tianqing and Qilu Pharmaceutical
.
According to statistics from Minaiwang, from 2013 to 2017, the domestic market for lenalidomide did not grow very fast, mainly due to the high price of imported drugs and some unacceptable domestic market
.
After the product entered the medical insurance in 2018, the market increased rapidly, especially in 2019, the sales of lenalidomide capsules rose to 710 million yuan
.
  

  Eliquis' generic drugs have received preliminary approval from the US FDA, but due to the settlement and key litigation last year, BMS/Pfizer will be able to withstand generic drug competitors at least until 2026
.
In 2020, the sales of apixaban was 9.
17 billion U.
S.
dollars, a year-on-year increase of 16%, making it one of the top five best-selling drugs in the world in 2020
.
  

  In fact, BMS and Pfizer have been working hard to fight against generic drug manufacturers for many years
.
For example, in 2017, BMS and Pfizer initiated patent infringement lawsuits against 25 companies that applied for the listing of Eliquis generic drugs
.
In August of the same year, the U.
S.
Patent and Trademark Office granted Eliquis a key substance component patent, extending the patent term from February 2023 to November 2026
.
The drug also has a formula patent, which will not expire until 2031
.
  

  In order to meet the "patent cliff" challenge, BMS has also expanded its R&D line and increased its diversification
.
The main newly launched products include: the world's first red blood cell maturation agent approved in 2019, and the first new drug for myelodysplastic syndrome approved in the past 10 years, Reblozyl; approved in March 2020 for the treatment of multiple The sclerosing new generation of highly selective S1PR1/5 inhibitor Ozamod (Zeposia); the micro-innovative formulation of oral azacitidine (Onureg) approved in September 2020 is the first to be extended as a first-line maintenance therapy overall survival of acute myeloid leukemia drugs
.
The above three new drugs will bring a total of 138 million U.
S.
dollars in revenue in 2020, which is a key force driving BMS's future performance growth
.
  

  In addition to the world's top four best-selling drugs, Eli Lilly, Amgen, Novartis, Takeda, and Novo Nordisk all have products with sales of more than US$3 billion in 2020 and their patents will expire in the next ten years
.