How do Hengrui, Qilu, Luye and CSPC perform in the battle for the development of complex injections?

The development of complex injections has high technical difficulty, low conversion efficiency and clinical success rate, and has become one of the main technical barriers to the development of innovative drugs and generic drugs at home and abroad

According to the author’s preliminary statistics, the FDA has approved at least 35 types of liposomes, microspheres, and nanocomplex injection preparations.

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Liposome is a kind of artificial membrane, mainly prepared from natural or synthetic phospholipids (such as DLPC, DMPC, DPPC, etc.

Many foreign products have been launched

In 1995, the FDA approved the first liposome injection drug Doxil (doxorubicin hydrochloride liposome injection) for the treatment of ovarian cancer, AIDS-related Kaposi's sarcoma and multiple myeloma

Doxil (trade name Caelyx listed in the EU) reached a peak annual sales of US$600 million in 2001 and achieved great commercial success, which attracted more pharmaceutical companies to enter the liposome field

  Ambisome (Amphotericin B liposome for injection) was approved in 1997 for the treatment of deep fungal infections, Depodur (morphine sulfate liposome injection, 2004) and Exparel (bupivacaine liposome injection, 2011) Enter the market as an anesthetic

Keep up with the domestic

  In China, the original variety of doxorubicin hydrochloride liposome injection was imported to China (trade name is Kailai/Caelyx), and it was not re-registered after the registration number expired in 2015

  At present, CSPC Ouyi Pharmaceutical, Changzhou Jinyuan Pharmaceutical, and Shanghai Fudan Zhangjiang Biotechnology have obtained 6 approval numbers for the generic drug of doxorubicin hydrochloride liposome injection

  A pharmaceutical company from Shanghai Shangyao Xinya Pharmaceutical Co.

  Hengrui Medicine's application for the marketing of the generic drug of bupivacaine liposome injection was accepted by CDE in April this year

  Several other products-morphine sulfate liposome injection, vincristine sulfate liposome injection, daunorubicin cytarabine liposome for injection, the original research has not yet been listed in the domestic market or applied for registration.

  Microspheres are small spherical particles, usually 1 micrometer to 300 micrometers in diameter

More than ten kinds of sustained-release microspheres have been approved by the FDA

  The first sustained-release microsphere, Lupron depot (leuprorelin acetate microsphere for injection) approved for marketing in the United States, was developed by Takeda (in cooperation with AbbVie)

  At present, more than ten kinds of sustained-release microsphere injections have been approved by the FDA for marketing
.
For example, Sandostatir Lar (Otreotide Acetate Microspheres for Injection) solves the short biological half-life of peptide drugs, extends the administration period to 4 weeks and improves patient compliance
.
Risperdal Consta (Risperidone Microspheres for Injection) solves the problem of drug treatment and drug abuse in patients with mental illness
.

Many original research varieties have been imported into China

  In China, the original varieties of leuprolide acetate microspheres for injection have been imported into China
.
Shanghai Livzon Pharmaceutical obtained the approval number of the generic drug of Leuprolide Acetate Microspheres for Injection
.

  The original varieties of octreotide acetate microspheres for injection have been imported into China
.
Teva/Kaixin Yuanda and Livzon Group’s generic applications for octreotide acetate microspheres for injection were accepted by CDE in February and August last year, respectively
.

  The original varieties of risperidone microspheres for injection have been imported into China
.
In January of this year, Luye Pharma’s risperidone microspheres (II) (Recinto) for injection developed by Luye Pharma have been approved for marketing by NMPA.
It is the company's first approved and marketed innovative formulation developed by a long-acting sustained-release platform
.

  In addition, exenatide microspheres for injection, triptorelin pamoate for injection, and original sulphur hexafluoride microbubbles for injection have been imported into China
.
  

  Nanoparticles are microscopic particles with at least less than 100nm
.
Since the 1990s, nanoparticle drug delivery systems have attracted attention
.

More than ten products have been launched in the U.
S.

  Paclitaxel's albumin-bound nanoparticle preparation Abraxane (paclitaxel for injection (albumin-bound type)) has achieved great commercial success in the treatment of recurrent breast cancer
.
Abraxane has obvious advantages over pure paclitaxel
.
In addition, Abraxane does not contain phospholipids, which can avoid the hemolytic reaction of liposomes
.

  Today, more than ten nanoparticle injection products have been approved for marketing in the United States
.
Among these products, several drugs with new technologies have attracted widespread attention
.
Invega Trinza (palmpaliperidone ester injection (3M)) with nanocrystal technology will be released slowly over a long period of time.
Sublocade (doxycycline hydrochloride gingival system) with Atrigel technology’s in-situ gel forming system The controlled release drug delivery system) is considered to be an epoch-making product
.

Domestic companies have joined

  In China, the original varieties of paclitaxel for injection (albumin-bound type), paliperidone palmitate injection, and palm paliperidone ester injection (3M) have been imported into China
.
The original import application for aripiprazole long-acting intramuscular injection was accepted by CDE in March this year
.

  At present, four pharmaceutical companies, namely CSPC, Hengrui, Qilu and Hunan Kelun, have obtained the approval number of paclitaxel (albumin-binding) generic drugs for injection and have been included in the Chinese Drug Catalogue
.
In addition, 3 companies including Yangzijiang Pharmaceuticals submitted applications for the listing of generic drugs for this product
.

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Conclusion <<<

  Among the 35 complex injections (liposomes, microspheres, nano) approved by the FDA, only 5 generic drugs have been approved for marketing in China
.
With the accumulation of relevant domestic enterprise technology and more pharmaceutical companies entering this field, the types of complex injections will be increasingly developed
.
It cannot be ignored that more and more complex injection products developed by foreign generic drug companies are also accelerating their entry into the Chinese market
.