O drug terminated two clinical trials, GSK and Merck parted ways, Gilead's $5 billion cooperation too failed?

From BMS to Merck and AstraZeneca, global pharmaceutical giants seem to be caught in a vicious circle of "clinical development failure" from sweet cooperation to parting ways
.

1+1 is not necessarily greater than 2

1+1 is not necessarily greater than 2

Nektar, which reached a $3.
6 billion partnership with BMS, recently suffered two failed clinical studies
.

On March 14, BMS and Nektar jointly announced the results of the first analysis of the Phase III clinical trial PIVOT IO-001 study
.

This study evaluated the efficacy of biased IL-2 bempegaldesleukin combined with PD-1 monoclonal antibody nivolumab (Opdivo) in the first-line treatment of unresectable or metastatic melanoma.

At the same time, BMS and Nektar will also terminate enrollment and unblind the ongoing PIVOT-12 study of the combination therapy for adjuvant melanoma, and patients in both studies will be informed about the treatment they received in the trial, After consultation with the doctor, the adjustment of the follow-up treatment plan was decided
.

Since the official announcement of a global development strategy totaling US$3.
6 billion in 2018, the cooperation between BMS and Nektar in the development of combination cancer therapies has continued to deepen, especially Nektar's long-acting IL-2 immunostimulatory therapy bempegaldesleukin (NKTR-214) and Opdivo's The combination has been granted breakthrough therapy designation by the FDA for the treatment of patients with unresectable or metastatic melanoma
.

In addition, NKTR-214 has been granted orphan drug designation by the FDA for the treatment of stage IIb to IV melanoma

Although two clinical trials for the treatment of melanoma have been terminated, the combination therapy of bempegaldesleukin and Opdivo is still underway in four other studies, including muscle-invasive bladder cancer, renal cell carcinoma, and head and neck squamous cell carcinoma.
Preliminary findings from two clinical trials in renal cell carcinoma and urothelial carcinoma are scheduled for publication in the first half of this year
.

As the two "leaders" of immunotherapy, the day after BMS announced that the O-drug combination therapy suffered a clinical trial failure, Merck announced the termination of the K-drug combination therapy clinical trial
.

Yesterday, Merck announced that the combination of its blockbuster Keytruda and AstraZeneca's PARP inhibitor Lynparza failed to outperform the currently commonly used anti-androgen in previously treated patients with metastatic castration-resistant prostate cancer (mCRPC).
Hormone therapy, decided to discontinue the development of Keytruda-Lynparza combination therapy
.

Trial results showed that the Keytruda-Lynparza combination failed to further prolong the lives of mCRPC patients or halt tumor progression compared with Johnson & Johnson Zytiga or Pfizer Xtandi
.

It is worth noting that, as the world's best-selling PD-1 and best-selling PARP inhibitors, K drug and Lynparza are both leaders in their respective therapeutic fields

Even worse, the Keytruda-Lynparza combination led to an increased incidence of grade 3-5 drug-related serious side effects in mCRPC patients
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After the disastrous results of the interim analysis of the Phase III Keylynk-010 trial, Merck decided to follow the recommendations of the independent data monitoring committee and stop the combination therapy development trial as soon as possible

Nine deaths and no regrets

Nine deaths and no regrets

If you sort out the R&D pipelines of global pharmaceutical giants today, it is not difficult to find that the expansion of their own new drug R&D pipelines through acquisition, investment, authorization and cooperation is a strategy that large pharmaceutical companies generally choose in the process of accelerating their drug R&D
.

On the one hand, for drugs already on the market, the combination is used to seek opportunities to expand the scope of indications and improve the effect of monotherapy; Drugs with clinical trial data of treatment regimens are incorporated into their own R&D system through project authorization, introduction or acquisition, or investment in companies, and cultivated to become the next performance growth point
.

Although this kind of external cooperation can quickly supplement its own pipelines, the projects that big pharmaceutical companies have invested in huge capitals of hundreds of millions of dollars or even billions of dollars in the early stage are faced with the failure of clinical trials, changes in the market competition pattern, and adjustment of the focus of project research and development.
Uncertainty like the "bamboo basket to draw water" in cooperation and research and development
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Just like Gilead, whose $5 billion cooperation was almost completely in vain, the 10-year cooperation with Galapagos is almost regarded as one of the most failed deals in recent years
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In July 2019, Gilead and Galapagos announced the signing of a 10-year global R&D cooperation agreement
.

Gilead acquires Galapagos an innovative portfolio of compounds, including six molecules currently in clinical trials, more than 20 preclinical programs, and an experience through a $3.

The beginning of a partnership is often promising and confident
.

There are multiple reasons for Gilead to reach this cooperation
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As early as 2015, Gilead reached an agreement with Galapagos totaling up to $2 billion to jointly develop Filgotinib, which was discovered by Galapagos

Not just Filgotinib, Galapagos also has two FIC grade compounds - GLPG1690 and GLPG1972
.

GLPG1690 is clinically used for the treatment of idiopathic pulmonary fibrosis, and the data shows that it is superior to the existing treatment regimens in the Phase IIa clinical trial; GLPG1972 is clinically developed for the treatment of osteoarthritis, in the early clinical 1b trial Positive preliminary top-line study data was obtained

However, in the face of the development of new drugs in the face of nine deaths, everything is unknown
.

Entering 2020, the cooperation between Gilead and Galapagos is like entering a Mercury retrograde period
.

First, the JAK inhibitor Filgotinib, which spent US$80 million to purchase priority review vouchers to accelerate the approval, was rejected by the US FDA.

The failure of the clinical study will hit both sides into 2021
.
The Phase III ISABELA trial of another partner drug, GLPG1690, in patients with idiopathic pulmonary fibrosis (IPF) also suffered termination
.
The Independent Data Monitoring Committee believes that the profit-risk profile of GLPG1690 no longer warrants further development
.
At the same time, the parties also discontinued all clinical trials of GLPG1690, including the long-term expansion of the Phase IIa NOVESA study in diffuse cutaneous systemic sclerosis
.
This is also seen as a possible "security issue"
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The failure of the clinical trial of another candidate drug SIK2/3 inhibitor GLPG3970 of the two parties in the field of rheumatoid arthritis/ulcerative colitis has been included in the list of the top ten clinical failure cases released by Fiercebiotech in 2021
.
Although the cooperation between the two parties is still in progress, the 10-year cooperation planned by the two companies may be terminated early in view of the potential safety hazards of the cooperative drugs and the pressure brought by changes in the market competition pattern
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In fact, it is not uncommon for cooperation to be terminated due to problems such as poor clinical data, changes in the market structure, and potential safety hazards
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In 2021 alone, many MNCs such as Roche, Merck, GSK, Johnson & Johnson have chosen to terminate their transactions with their respective project partners due to poor clinical trial data
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The termination of the cooperation between Roche and Atea on the oral new crown drug AT-527 is the transaction with the highest down payment in the past year.
Commercialize rights to AT-527 with upfront payment of $350 million, future milestone payments and royalties
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One year later, on November 17, 2021, Atea announced the termination of the joint development of the new crown oral drug AT-527 project with Roche.
The reason for the termination of the cooperation may be related to the poor phase II clinical results of AT-527
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The failure of GSK and Merck to develop the bifunctional fusion protein Bintrafusp alfa that combines anti-PD-L1 and TGF-β inhibition also makes the industry regret
.
The excellent clinical data of Bintrafusp alfa in the past made this therapy publicized as a strong competitor of Keytruda in the future, but Bintrafusp alfa suffered four failures of Phase II/III clinical studies in the past year, forcing GSK and Merck to terminate the research and development
.
This powerful alliance with a down payment of 300 million euros and a total transaction value of 3.
7 billion euros has also stopped
.
The termination of the Bintrafusp alfa R&D project has made many "followers" re-examine the value of PD-L1/TGF-β dual antibody clinical research
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According to data, among the top ten multinational pharmaceutical companies in the world, 60% to 70% of their products enter the pipeline through external cooperation
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A person in charge of a domestic pharmaceutical company once told the E-pharmaceutical manager that although they face huge research and development risks, the search for new blockbuster drugs and new driving forces for performance growth are related to the survival and development of large pharmaceutical companies
.
Licensing cooperation is currently the most popular innovative model.
Big pharmaceutical companies can quickly replenish their pipelines and even grasp the opportunities for research in some disease fields and new targets through "buy, buy, buy" licensing transactions
.