February 2021 | TOP5 failed clinical studies

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Based on the industry news section of the Medical Rubik's Cube website, NextPharma database and public information, the February 2021 "Clinical Research Monthly" has screened out 5 studies that are worthy of attention that have not reached the primary clinical endpoints for your reference.

1.

The KESTREL study is a randomized, open-label, multi-center, global phase III clinical study designed to evaluate durvalumab or durvalumab combined with tremelimumab vs.

According to PACIFIC and CASPIAN studies, Imfinzi has been approved for unresectable stage III non-small cell lung cancer (NSCLC) and extensive stage small cell lung cancer (SCLC).

As part of a broad development plan, Imfinzi is being used as a monotherapy or in combination with other anti-cancer therapies such as Tremelimumab for NSCLC, SCLC, hepatocellular carcinoma (HCC), biliary cancer, esophageal cancer, gastric cancer and gastroesophageal cancer, etc.

2.

However, in the early morning of the 9th, Biotech made another announcement, announcing the termination of the clinical trial of BAT8001 for HER2-positive breast cancer.

This study is a domestic multi-center, randomized, open, positive-controlled, phase III clinical study of superiority.

Regarding the reasons for the termination, the explanation given in the announcement by Biotech is: “This drug will be difficult to gain an advantage in the competition with many targeted anti-tumor drugs.

Biotech has invested 226 million yuan in the BAT8001 project.

HER2 is one of the most competitive targets in China.

3.

At the same time, the two companies pointed out that they will also stop all clinical trials of Ziritasestat, including the long-term expansion of the Phase IIa NOVESA study in diffuse skin systemic sclerosis.

Ziritaxestat (GLPG1690) is an autotaxin inhibitor of lysophosphatidic acid (LPA).
Autotaxin acts as an extracellular enzyme to catalyze the synthesis of various LPA (different fatty chains).
LPA is an important signal molecule that has multiple functions in immune response and maintaining tissue homeostasis.
Although LPA seems to have a certain role in promoting pulmonary fibrosis, its function in other tissues is not clear.
IPF is a disease with a high fatality rate, even more than many tumors, with a 5-year survival rate of about 20%.
There are few therapeutic drugs for IPF.
Except for BI's Ofev and Roche's Esbriet acquired from Intermune, no other innovative drugs are on the market.

Gilead entered into a 10-year global R&D partnership with Galapagos in July 2019, paid US$3.
95 billion in advance and US$1 billion in equity investment, obtained the license right of Ziritaxestat, and began to share the development costs of the third phase.
.
In addition to Ziritaxestat, Gilead also favors Filgotinib.
In August 2020, the FDA issued a complete response letter (CRL) to Filgotinib's new drug application for safety reasons.
Now the two companies have abandoned the clinical registration of Filgotinib in the United States.
the study.
Looking back, this $5 billion cooperation may become the most failed biotechnology transaction in recent years.

4.
Phase I/II and Phase III studies of LentiGlobin gene therapy for sickle cell disease (SCD)

On February 16, Bluebird Bio announced that due to suspected unanticipated serious adverse reactions acute myeloid leukemia (AML), the company has suspended LentiGlobin gene therapy for sickle cell disease (SCD) phase I/II (HGB-206).
) And Phase III (HGB-210) clinical studies.

Bluebird said it is investigating the cause of the subject suffering from AML to determine whether it has any relationship with the use of BB305 lentiviral vector in the production of LentiGlobin gene therapy.
In addition, Zynteglo, a product that also uses the lentiviral vector BB305 and has been marketed in Europe for the treatment of thalassemia, has been affected, and its sales have been suspended.
Affected by this news, Bluebird's shares fell nearly 40% that day, closing at 28.
44 US dollars.

Gene therapy and oncolytic viruses are relatively hot fields in recent years, and many pharmaceutical giants have related layouts.
However, more companies currently choose to use adeno-associated virus (AAV).
Although the probability of integrating into human genetic material is lower than that of lentiviral vectors, there are similar concerns.

This time, although the viral vector DNA was found in the tumor cells of AML patients, whether there is a direct relationship between the BB305 lentiviral vector and the occurrence of AML needs further investigation and confirmation; in addition, the HGB-206 group C patients developed bone marrow Hyperplasia syndrome (MDS) also contributed to the suspension of this trial.

5.
Phase III study of Otividex in the treatment of Meniere's disease

On February 22, Otonomy announced that the phase III clinical trial of Otividex for the treatment of Meniere's disease (formerly known as Meniere's disease) did not meet the primary endpoint.
Affected by this news, Otonomy stock fell 44% to close at $3.

Meniere’s disease is an idiopathic inner ear disease.
The main pathological change is membrane labyrinth hydrops.
The clinical manifestations are recurrent rotational vertigo, fluctuating hearing loss, tinnitus and ear fullness, which can cause permanent Hearing loss.
Otividex is a sustained-release preparation of dexamethasone.
The trial is a prospective, randomized, double-blind, placebo-controlled Phase III study in the United States and Europe.

In 2017, Otonomy announced that Otividex had reached the primary endpoint in its Phase III clinical trial for the treatment of Meniere's disease, and will discuss with the FDA the clinical research and development required to apply for Otividex's listing requirements.
It now appears that the early analysis results have not been recognized by the FDA.

In July 2020, Otonomy submitted a revised statistical analysis plan for the trial to the FDA, proposing to use a negative binomial model to conduct preliminary analysis of the daily vertigo count data reported by patients.
Otonomy believes that this statistical model can provide the most suitable clinical data method for Otividex based on the two comprehensive data sets of Phase IIb (AVERTS-2) and Phase III clinical trials.
However, using the negative binomial model, in the intention-to-treat (ITT) population (n=148; p=0.
312), Otividex was compared with placebo on the primary endpoint of vertigo days (DVD) determined in the third month Did not reach a significant advantage.