Dry! Bicken Prenol Drug Study Report

The 2022 Pujiang Innovation Forum Global Health and Development Forum reported that there were 1.
5 million new HIV infections worldwide in 2021, with an average of 4,000 people living with HIV every day
.
According to the "Progress in HIV/AIDS Epidemiological Research in China" released by the Chinese Center for Disease Control and Prevention in 2021, by the end of 2020, a total of 1.
053 million people in China had been infected with HIV, and a cumulative total of 351,000
deaths had been reported.
According to the data, the AIDS situation is relatively serious
, both domestically and globally.

Worldwide, there is still a lack of effective drugs
to cure HIV infection.
The goal of treatment at this stage is to maximize and sustain viral replication in patients, so that patients can re-establish and maintain immune function, while reducing the morbidity and mortality
of HIV infection and non-AIDS-related diseases.
At present, the main drugs used to treat AIDS are antiviral drugs, and Bicken Pronode is one of
the most popular treatment drugs at present.

Mechanism of action

Bicken Propanol Tablets (B/F/TAF) is a fixed-dose combination
of the antiretroviral drugs bic tepiravir (BIC), emtricitabine (FTC) and tenofovir propofovir propofovir (TAF).

Bictegravir: Bictegravir is an integrase chain transfer inhibitor (INSTI) that inhibits the chain transfer activity
of HIV-1 integrase, an enzyme encoded by the HIV-1 virus that is required for viral replication.
Inhibition of integrase prevents the integration of linear DNA into host genomic DNA, blocking HIV-1 proviral formation and viral proliferation
.

Emtricitabine: Emtricitabine is a synthetic cytidine nucleoside analog phosphorylated by cellular enzymes to form emtricitabine 5'-triphosphate, which terminates DNA strand synthesis by competing with the natural substrate 5'-triphosphate deoxy into nascent viral DNA, thereby inhibiting HIV-1 reverse transcriptase activity
.
Emtricitabine 5'-triphosphate is a weak inhibitor
of mammalian DNA polymerase α, β, ε and mitochondrial DNA polymerase γ.

Tenofovir propofovir: tenofovir propofovir propofovir is a phosphoramide prodrug of tenofovir (2'-dehydroadenosine monophosphate analogue), the tenofovir propofovir exposed in plasma can penetrate into cells, and then tenofovir propofovir is hydrolyzed to tenofovir by cathepsin A in the cell, and then tenofovir is phosphorylated by cytokinase to the active metabolite tenofovir
bisphosphate.
Tenofovir diphosphate is embedded into viral DNA by HIV reverse transcriptase, resulting in DNA strand termination
.
Tenofovir bisphosphate is a weak inhibitor of mammalian DNA polymerase, including mitochondrial DNA polymerase γ, but there is no evidence
of toxicity to mitochondria in cell culture.

Pharmacokinetics

1) In a thorough QT/QTc trial in 48 healthy subjects, BIC at doses 1.
5 and 6 times the recommended dose did not affect the QT/QTc interval and did not prolong the PR interval
.
In a thorough QT/QTc trial in 48 healthy subjects, TAF at the recommended dose or at a dose 5 times the recommended dose did not affect the QT/QTc interval and did not prolong the PR interval
.
The effect of FTC on the QT interval is unknown;

2) effect on serum creatinine;

3) Healthy subjects receiving BIC 75 mg (1.
5 times the approved recommended dose) once a day with food for 14 days, serum creatinine compared with placebo changed from a baseline mean of 0.
1 mg/dL on days 7 and 14
.
BIC had no meaningful effect
on estimated creatinine clearance or true glomerular filtration rate (as determined by probe drug, iohexol clearance).

Clinical application

The current global predomination of Bickenpreferol tablets is as a complete regimen for the treatment of adults with human immunodeficiency virus type 1 (HIV-1) infection and there is no current or previous evidence of
viral resistance to integrase inhibitors, emtricitabine, or tenofovir.

In the United States, Bicken Pronols tablets have been expanded for use in children with HIV-1 infection who have achieved virologic suppression or have just started antiretroviral drug (ARV) therapy with a body weight of at least 14 kg to less than 25 kg
.

At present, the global competition for the same target drugs is not fierce, and the research and development of competing drugs is also dominated by the original research company Gilead Sciences, and it is expected that the later Bicken Pronolium tablets will be used as the main drug
for HIV-1 IN targets and Nucleoside reverse transcriptase targets for a long time.

Biktarvy listing

At present, Biktarvy is listed in China, the United States, Japan and the European Union, and its relevant listing status is as follows:

Global R&D progress of co-target drugs

(1) Research and development of HIV-1 IN target

Globally, 6 drugs targeting HIV-1 IN have been successfully marketed, 2 drugs are in clinical phase I.
, and 13 drugs are in the preclinical stage
.
From the perspective of enterprises, Gilead Sciences is the most important R & D enterprise, which has 3 drugs of this target that have been approved for marketing, 1 is in clinical phase I.
, and 4 drugs are in preclinical
practice.

(2) Research and development of Nucleoside reverse transcriptase

Nucleoside reverse transcriptase is an important target for the development of antiretroviral drugs for the treatment of HIV, and 42 drugs with this target have been marketed, 18 drugs are in clinical stage, and 3 are preclinical drugs
.
From the company's point of view, Gilead Science of the United States is still the most developed enterprise
with 8 listed drugs and 1 drug under development.

Progress in R&D of co-target drugs in China

(1) Research and development of HIV-1 IN target

In China, 2 drugs targeting HIV-1 IN have been successfully marketed, and 1 drug is in clinical phase
III.
Among them, the drugs that have been marketed are Gilead's Bicken Pronorol tablets and Merck's raltegravir potassium, and the clinical-stage drug is GlaxoSmithKline's dolutegravir
.

(2) Research and development of Nucleoside reverse transcriptase targets

According to statistics, Nucleoside reverse transcriptase (nucleoside reverse transcriptase) has 7 related drugs on the market in China, in addition to 7 clinical registration applications, 1 drug in clinical stage, and 1 preclinical drug
.
From the company's point of view, Gilead Sciences of the United States is the most important enterprise
of Nucleoside reverse transcriptase target drugs in China with 5 listed drugs and 1 drug under development.

In terms of market, Bicken Pronorium tablets are a blockbuster drug in the field of HIV treatment and a representative product of Gilead Sciences, with a market share far exceeding other similar drugs
.
The excellent market performance also shows that the drug is currently very popular
in HIV treatment.
In addition, the drug has made Gilead Sciences the absolute leader in HIV treatment
.

Market situation of Bicken Prenolium tablets

According to the information released by Gilead every year, the sales of Bicken Propanolium tablets since their launch are as follows
.
With its remarkable efficacy, the sales of Bicern Prenols tablets exceeded one billion US dollars in the first year of marketing, and it has become the largest selling drug in the field of HIV in the second year of marketing, with a compound annual growth rate of 93.
84%
in the past four years.

The world's leading therapeutics

According to related reports, the global scale of HIV drugs in 2021 will be about 38 billion US dollars
.
After the data query of pharmacointelligence, the sales of Bicken Prenolium tablets reached 8.
624 billion US dollars, accounting for 23%, which is the largest drug in the market of HIV treatment drugs, and close to 3 times
that of Jiefucan, the second drug in the field of HIV.

Although Bickenprenol tablets have only been on the market for four years, they have become the most important HIV treatment drug
today.
This is also mainly based on the following factors:

1) Bicken Pronolium tablets themselves show very good efficacy, which is the smallest triple compound single tablet preparation among the existing integrase inhibitors, which greatly improves medication compliance, and has good antiviral efficacy, high drug resistance barrier and smaller toxic side effects than Biken Pronol;

2) It can be seen from the market situation that the market concentration of HIV drugs is very high, indicating that there are still a lot of clinical unmet needs for HIV treatment drugs, and when a relatively excellent drug appears, it can be quickly accepted by the market;

3) Gilead itself is an important player in the field of HIV treatment, and has great advantages
in research and development, marketing and promotion.

The case of Bicken Prenolium tablets can provide some reference for domestic pharmaceutical companies to expand in the field of HIV treatment, first of all, the market in the field of HIV is very broad, and there is a very large unmet demand, and the market acceptance is very high
.
Secondly, the compound preparation of Bicern Pronol, which treats HIV through multi-angle and multi-link combination drugs that inhibit HIV, can be used as an important direction
for the development of HIV drugs.