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How to extend the life cycle of the original drug product? Rely on these three points

 Last Update: 2023-01-06
 Source: Internet
 Author: User

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The research and development of original research drugs is a long process, which requires huge funds and tens of millions of tests before it can be finally delivered to the regulatory authorities for approval, and only after passing the strict review of the regulatory authorities can it be finally marketed
.

From the establishment of a project to the final launch, a drug can be described as experiencing thousands of difficulties and nine deaths
.
Every product has a life cycle, and pharmaceuticals are no exception
.
After painstaking efforts to obtain a new drug, any manufacturer wants to do everything possible to extend its life cycle and obtain greater returns
.
In order to defend hard-won R&D achievements, original drug companies will find ways to extend their life cycle
.
This article will sort out the strategies
commonly used by original pharmaceutical companies to extend the product life cycle.

From the establishment of a project to the final launch, a drug can be described as experiencing thousands of difficulties and nine deaths
.
In order to defend hard-won R&D achievements, original drug companies will find ways to extend their life cycle
.
This article will sort out the strategies
commonly used by original pharmaceutical companies to extend the product life cycle.

1 Add new medicinal uses

There is a narrow and broad sense of new medical uses
.
In a narrow sense, new pharmaceutical uses refer to the addition of new indications for existing marketed drugs; In a broad sense, new drug use refers to increasing the drug use methods and their combinations
such as the target of administration, the mode of administration, the route of administration, the dose, and the frequency.

In the United States, two new pharmaceutical uses, narrow and broad, can not only obtain legal protection extension, that is, extend the term of product protection by obtaining patent authorization, but also obtain administrative protection, that is, increase the market exclusivity period of the drug to extend the term of protection of the product
.
Generally speaking, companies will choose one or two indications that are most grasped to advance quickly in order to obtain early approval; At the same time, research on other indications, drug delivery objects, delivery methods, routes of administration, doses, frequencies and other drug use methods and their combinations are also being carried out simultaneously, and new drug uses are planned to be added according to research progress, thereby expanding the scope of
applicable populations.

The two new pharmaceutical uses in the narrow and broad sense can not only obtain legal protection extension, that is, the extension of the term of product protection by obtaining patent authorization, but also administrative protection

Adalimumab injection is the world's first fully human anti-tumor necrosis factor monoclonal antibody
approved for marketing.
AbbVie's financial report shows that Humira's sales reached $20.
696 billion in 2021, which is also the first time that Humira exceeded $20 billion
.
Since becoming the global sales champion with 9.
48 billion US dollars in 2012, it has dominated the list for many years and is a veritable "medicine king"
.
Since its launch, Humira has been approved worldwide for 17 indications, such as rheumatoid arthritis (RA), juvenile idiopathic arthritis (JIA), psoriatic arthritis (PsA), ankylosing spondylitis (AS), adult Crohn's disease (CD), Crohn's disease in children, ulcerative colitis (UC), plaque psoriasis (PsO), hidradenitis purulentis (HS), uveitis (UV), etc
.
These new indications have contributed to the extension of the product life cycle and greatly expanded its range of
applications.

Sacubitril valsartan sodium tablets (trade name Entresto) is Novartis' blockbuster product for heart failure, with sales of more than $3.
5 billion in 2021 and a 33%
increase in sales in the first half of 2022.
The product was approved by the FDA in July 2015 for chronic heart failure with reduced ejection fraction, and then expanded to pediatrics through clinical trials of Novartis, and then through new clinical studies, Novartis further expanded the clinical indication and adjusted the initial dose in some patients
.
Based on these studies, Novartis obtained a further extension of the market exclusivity period, from October 1, 2022 to February 16
, 2024.

2 Development of new dosage forms

The research and development of new dosage forms not only increases patient compliance and improves the drawbacks of clinical drugs, but also extends its life cycle through iterative upgrading of products, and has now become the usual means
for original manufacturers to extend the lifeline of products.

More typical examples are aripiprazole
in Otsuka in Japan.
Aripiprazole is a new atypical antipsychotic drug known as a "dopamine system stabilizer"
.
FDA first approved aripiprazole ordinary tablets in November 2002, and Otsuka Pharmaceutical has continued to innovate preparations, successively approving oral solution, oral disintegration tablet, ordinary injection, long-acting injection (1 time/month) and digital tablet with built-in chip
.

On September 13 of this year, Otsuka Pharmaceutical and Lundbeck jointly announced that the FDA had accepted the ready-to-use 2-month long-acting injection of aripiprazole 2-month，Ready-to-Use，Long-acting Injectable) for the treatment of bipolar I disorder and adult schizophrenia
.
It has been a full 20 years since it was first approved for marketing, and through continuous dosage form upgrades, aripiprazole continues its immortal legend
.

It has been a full 20 years since it was first approved for marketing, and through continuous dosage form upgrades, aripiprazole continues its immortal legend
.

3 Weaving patent protection nets

The competition of new drugs is essentially a competition of economic strength and scientific and technological strength, and the results of drug research and development can only achieve greater benefits
in the market through good patent protection.
In all technical fields, the biopharmaceutical industry has the highest dependence on intellectual property rights, and the protection of pharmaceutical intellectual property rights by domestic and foreign biopharmaceutical enterprises also runs through the whole process
of drug research and development.
There is even a saying that "to make medicine is to make a patent"
.
If the original drug expires, there will be a "patent cliff"
immediately.

In all technical fields, the biopharmaceutical industry has the highest dependence on intellectual property rights, and the protection of pharmaceutical intellectual property rights by domestic and foreign biopharmaceutical enterprises also runs through the whole process
of drug research and development.

Like the former "drug king" Lipitor, after entering the "patent cliff" in 2011, it quickly fell from a peak of nearly 13 billion US dollars in annual sales to single-digit sales
.
In order to maintain the market position of the original drug, the original manufacturer usually weaves a tight patent protection network, and obstructs the listing
of generic drugs to the greatest extent through three-dimensional, cross-border and all-round patent protection.

Still take Humira as an example
.
Since applying for its first patent in 1994, Humira has applied for a total of 386 patents (including 247 US patents)
in the United States, Europe and Japan in 2018.
Related patents involve antibody-related products, indications, preparation methods, preparations, treatment methods, devices and efficacy evaluation, among which indications and preparation method patents account for a large proportion
.

Although the core structure patent of adalimumab expired in 2016, AbbVie perfectly continued the protection
of Humira products through the layout of preparations, preparation methods, indications, etc.
Coveting the huge market of Humira, a number of pharmaceutical companies, including Amgen, have filed marketing applications and patent challenges for Humira biosimilars to the FDA
.
However, due to AbbVie's patent layout, they could only sign a settlement agreement with AbbVie, according to the terms of the agreement, these companies' biosimilars can land in the United States at different times as early as 2023, and will not be brought forward
due to the listing of other licensed products.

The signing of these agreements means that AbbVie has achieved a comprehensive victory in defending Humira's franchise in the United States, and the basis for these agreements is AbbVie's solid patent layout
for Humira Pharmaceuticals.
A case in point is Boehringer Ingelheim's patent challenge, which was violently countered by AbbVie, suing Boehringer Ingelheim's Humela biosimilars for infringing 1,600 claims
on 74 different patents.
With so many barriers to patenting, this is a great deterrent to potential challengers
.
Patent litigation is a time-consuming and costly process, especially for biosimilar manufacturers, the long patent litigation cycle will lead to the market of their products far away, "the lesser of two evils", biosimilar manufacturers have to accept a settlement with AbbVie, in order to delay the conditions of listing in the United States in exchange for markets
outside the United States.

Patent litigation is a time-consuming and costly process, especially for biosimilar manufacturers, where lengthy patent litigation cycles will result in a long time to market

4 Summary

As a knowledge-intensive industry, the biomedical industry has high entry thresholds, large R&D investment, long cycles, high risks and high
returns.
In order to obtain maximum benefits, innovative drug companies continue to tap the potential of drugs and expand the scope of application through continuous R&D investment, and greatly promote the continuation of their own product life cycle while solving unmet clinical needs, which can be described as a win-win
.

References:

1.
For the treatment of bipolar disorder, the marketing application of aripiprazole 2-month long-acting injection was accepted by the FDA

2.
Aripiprazole: the life cycle continuation of bombshell drugs

3.
Novartis filed another citizen petition with the FDA to prevent the approval of the generic drug for Entresto

4.
386 patent layout, more than double price growth in 4 years: Humira has achieved great commercial success, but it has also attracted criticism!

5.
HUANG Lu, QIAN Lina, ZHANG Xiaoyu, et al.
Patent protection and patent layout strategy in the field of medicine[J].
China Journal of New Drugs, 2017, 26(2):6.

6.
Chen Yanchuang, Li Ning.
Peripheral patent: a patent defense weapon for adalimumab (Humira) [J].
China Science and Technology Information, 2021(14):3.

7.
FDA website

8, Wu Kewei.
Concise Labeling and Determination of Patent Infringement for Second Medical Use: From Normative Construction to Standard Selection [J].
Science and Technology Progress and Countermeasures, 2022, 39(2):101-110.

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