ADC vs PDC——Inventory of current status of ADC-PDC drug research and development at home and abroad

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With the continuous efforts of China's pharmaceutical industry and the increasing attractiveness of China's pharmaceutical market to global innovative drugs, more innovative drug projects have begun to make listing on the Chinese market a mandatory item in their projects

Introduction to ADC Drugs

In recent years, ADC drugs have been the key direction of global anti-tumor drug technology development, as well as the research and development hotspots in the field of biomedicine, known as "intelligent biological missiles" and "magic bullets

PDC (peptide-drug conjugate), or peptide-drug conjugate, is a new type of conjugated drug that has also begun to attract attention in the field of research and development

Figure 1 The mechanism of action of ADC drugs

(Image source ADC Drug Research and Development Report 2020)

ADC drugs on the global market

Since Pfizer’s first ADC drug Mylotarg was launched in 2000, a total of 14 ADC drugs have been approved worldwide (see Table 1 for details)

Figure 2 ADC drug solid tumor antigen target

(Image source: British Journal of Cancer, 2016)

Table 1 ADC drugs approved worldwide

Since ADC entered the pharmaceutical market, its drug development technology has been continuously improving; from the perspective of drug composition and development technology, ADC drugs that have been on the market have undergone three generations of technological changes.

ADC drugs have significant clinical effects.

ADC drugs on the domestic market

Currently, there are 3 ADC drugs on the market in China: Roche’s Kadcyla (Enmetrastuzumab (trade name: Hercelium)) was approved for marketing in China in January 2020; Adcetris, a subsidiary of Takeda Pharmaceuticals, in May 2020 (Vibtuximab (trade name: Anshili)) was approved in China; in June 2021, Rongchang Bio's vedicitumumab was approved for marketing, which is the third ADC antibody drug approved in China , And also the first domestically produced ADC

In addition, in January 2021, Pfizer’s Besponsa (inotuzumab ozolamicin) submitted a marketing application in China, and was subsequently included in the priority review scope by CDE; Genting Pharmaceutical’s Gosartor group list in May 2021 Anti (targeting Trop2) also submitted a listing application in China

It is worth mentioning that in August 2021, Rongchang Biotechnology and Seagen reached an exclusive global license agreement for the development and commercialization of vedicitumumab.

Rongchang Bio is a pioneer in the domestic ADC track.

Figure 3 Rongchang Biological R&D pipeline

(Source: Rongchang Biological Official Website)

Although the research and development of ADC drugs in China started late, the market competition is quite fierce.

In addition, we should also pay attention to the R&D risks of innovative drugs.

The success and failure of PDC drugs

PDC (peptide-drug conjugate) is a new type of conjugated drug.

From the perspective of the global market, only two PDC drugs have been approved for listing.

On October 22, Oncopeptides announced the withdrawal of its peptide-conjugated drug Pepaxto (melphalan flufenamide) for the treatment of relapsed or refractory multiple myeloma in the US market, mainly because Pepaxto failed to reduce the ITT population in the confirmatory phase III OCEAN study The risk of death (HR=1.

PDC drug failure lesson-Pepaxto collapse

In February 2021, Pepaxto was approved by the FDA for accelerated listing, and used in combination with dexamethasone to treat patients with triple refractory/relapsed multiple myeloma

In May 2021, Oncopeptides announced the preliminary results of a head-to-head Phase III clinical trial (OCEAN) of Pepaxto combined with dexamethasone and pomalidomide combined with dexamethasone for the treatment of patients with relapsed and refractory MM.
Pepaxto combined with dexamethasone improved The patient’s PFS and ORR
.
But when the results were updated again in July this year, it showed that the OS data of the pomalidomide combined with dexamethasone control group was better
.

In July 2021, the FDA issued a safety warning against Pepaxto
.
The warning stated that Pepaxto's Phase III clinical trial (OCEAN, Study OP-103) results analysis showed that Pepaxto combined with dexamethasone in the treatment of relapsed and refractory multiple myeloma (RRMM) increased the risk of death
.
The FDA has recommended that medical personnel should review and analyze the disease progression of patients after taking Pepaxto, and then discuss with patients the risk of changing other treatment options to continue treatment
.
At the same time, patients taking Pepaxto should discuss the risks and benefits of taking Pepaxto with the attending doctor
.
At the same time, the FDA requested that OCEAN and Pepaxto other clinical trial patient recruitment be suspended
.

In the end, Oncopeptides chose to withdraw Pepaxto from the US market
.
This failure case should make more companies dedicated to the research and development of such drugs begin to think deeply about the safety of drugs
.

summary

Based on the above information and data, it can be seen that ADC drugs have entered the super hot spot that the industry is highly concerned about
.
The continuous efforts in the field of drug research and development have also made the research and development technology and evaluation standards of ADC drugs clearer
.
It can be predicted that this field will continue to attract R&D investment, and there will also be more excellent products appearing, providing more choices for patients
.

Although there are not many PDC drugs currently on the market, there have recently been cases of withdrawal from the market due to serious safety issues
.
However, the author believes that with the resolution of related technical problems and breakthroughs in supporting technologies, PDC drugs will also become a hot spot for research and development and a crowded track for investment in the next ten years
.

Reference materials:

1-The oncology market for antibody–drug conjugates

2-FDA official website

3-NMPA official website

4- Official websites of major pharmaceutical companies

5-Oncopeptides official website information