TOP10 failed clinical studies in August 2021

Article source: Med

Author: Leaf

Based on the industry news section of the Medical Rubik's Cube website, NextPharma database and public information, the "Monthly Clinical Research Report" in August 2021 has screened out 10 clinical studies worthy of attention that did not reach the primary endpoint for your reference

1.

Biophytis SA pipeline products (Source: BiophytisSA)

BIO101 is an oral small molecule.

BIO101 mechanism of action (Source: Biophytis SA)

The SARA-INT study aims to evaluate the safety and effectiveness of BIO101 in the treatment of age-related sarcopenia-induced muscle atrophy and inconvenience

2.

BiTE® is Amgen's immuno-oncology platform.

BiTE® platform products and application areas (Source: Amgen official website)

In addition to AMG 427, Amgen also reported the "bad news" of three other CD3 double antibodies in the 2020 performance report released in February this year, specifically: 1) BCMA target for the treatment of relapsed or refractory multiple myeloma Suspended the recruitment of BiTE molecule AMG 701 for phase I trial due to safety issues (cytokine release syndrome); 2) The clinical development of BiTE molecule AMG 673 that targets CD33 has been suspended; 3) EGFR variant III for the treatment of glioblastoma The clinical development of the targeting BiTE molecule AMG 596 was terminated (the reason is to consider the priority of the investment portfolio)

3.

Sensei pipeline products (Source: Sensei)

SNS-301 is the first generation of immune activation vaccine developed by Sensei using its ImmunoPhage™ pioneering vaccine platform.

SNS-301 drug manifestations (Source: Sensei)

4.

Lomecel-B is in research indications (Source: Longeveron)

Lomecel-B is an allogeneic cell product, which is composed of medicinal signaling cells (MSC) from adult donor bone marrow, and is cultured in a cell processing facility that complies with regulations (cGMP)

Lomecel-B mechanism of action (Source: Longeveron)

The study mainly evaluated the safety and effectiveness of four different doses of Lomecel-B cell therapy (25 million (n=37), 50 million (n=31), 100 million (n=34)) in a single peripheral intravenous infusion.

5.
Donafenib in the treatment of advanced colorectal cancer phase III clinical

On August 17, Zejing Pharmaceutical announced the results of two phase III clinical trials of Donafinil tosylate tablets.
The analysis of the results for the treatment of advanced colorectal cancer above second-line showed that Donafinil was compared with the control group.
The main efficacy index of median overall survival (mOS) did not reach the preset superiority target, and it was decided to terminate the further development of Donafenib monotherapy for this indication
.

The study is a randomized, double-blind, placebo-controlled multicenter trial (ZGDC3), enrolling a total of 536 patients.
The main purpose is to evaluate the effectiveness of Donafenib in the treatment of advanced colorectal cancer above second-line.
The secondary purpose is It is to investigate the safety and tolerability of Donafinil
.
Zejing Pharmaceuticals gave the preliminary reasons for the failure of the study: some patients in the control group did not use other therapeutic drugs in a standard manner; most of the patients in the group were end-line and the disease progressed rapidly; during the trial, after advanced colorectal cancer The standard treatment of the line has undergone major changes
.

Donafenib is an oral multi-target, multi-kinase inhibitor class of small molecule anti-tumor drugs
.
In June 2021, Donafinil was approved for the first-line treatment of advanced hepatocellular carcinoma indications
.
At present, the phase I trial of Donafenib tablets combined with daunorubicin and cytarabine in the treatment of recurrent acute myeloid leukemia (AML) is still in progress, and a number of combinations with tumor immunotherapy drugs have been launched to treat advanced tumors.
Research
.

6.
Phase Ⅲ study of Ultomiris in the treatment of amyotrophic lateral sclerosis

On August 20, AstraZeneca announced that its rare disease company Alexion has decided to terminate the global phase III clinical study (CHAMPION-ALS) of Ultomiris (ravulizumab) in adult amyotrophic lateral sclerosis (ALS)
.
The decision was based on the independent data monitoring committee (IDMC) after reviewing the pre-set interim analysis data, and found that it lacked efficacy and recommended that the trial be terminated
.

C5 complement inhibitor pipeline products (Source: Alexion)

Ultomiris (ravulizumab) is the first and only long-acting C5 complement inhibitor that works by inhibiting the C5 protein in the complement cascade
.
In 2018, Ultomiris was approved for the first time on the market, and is currently approved for the treatment of paroxysmal nocturnal hemoglobinuria and atypical hemolytic uremic syndrome (aHUS) in adults and children
.

In 2021, AstraZeneca completed the acquisition of Alexion in the form of US$39 billion in cash and stock, obtained a variety of rare disease product pipelines including Ultramiris, and officially entered the rare disease field
.
Amyotrophic lateral sclerosis (ALS) is a neurological disease characterized by the progressive degeneration of nerve cells (motor neurons) in the brain and spinal cord that control muscles throughout the body
.
When nerve cells die, the brain can no longer activate and control muscle movement, resulting in severe disability, paralysis and eventually death
.
As a randomized, double-blind, placebo-controlled multicenter global trial, the CHAMPION-ALS trial aims to evaluate the efficacy and safety of Ultomiris in the ALS population
.
The trial enrolled 382 adult patients with sporadic or familial ALS, and the primary end point was the change in scores assessed on the ALS Functional Score Scale (ALSFRS-R)
.

7.
Phase Ⅱb clinical study of Izencitinib in the treatment of ulcerative colitis

On August 23, Theravance Biopharma announced the top-line results of a phase IIb dose exploratory study of selective pan-Janus kinase (JAK) inhibitor Izencitinib for the treatment of ulcerative colitis
.
The data showed that compared with placebo, Izencitinib did not reach the primary endpoint of Mayo score change at week 8, or the key secondary endpoint of clinical remission
.

Key research data (Source: Theravance)

This multicenter, randomized, double-blind, placebo-controlled phase IIb dose exploration induction study (NCT03758443) aims to evaluate the clinical efficacy of oral Izencitinib once a day in the treatment of moderate to severe active ulcerative colitis in adults
.
At all doses, Izencitinib was well tolerated, without perforation, opportunistic infections, major cardiovascular or thromboembolic events, complex shingles or non-melanoma skin cancers
.

Theravance will also release the results of the 16-week extended induction and 44-week maintenance study of Izencitinib for ulcerative colitis
.
Theravance has reached a global joint development and commercialization agreement with Johnson & Johnson on Izencitinib (TD-1473) and other compounds for inflammatory bowel disease
.
Theravance received an upfront payment of US$100 million and is eligible for potential payments of up to US$900 million
.

8.
Phase II study of M7824 in the treatment of biliary tract cancer

On August 23, Merck announced that based on the IDMC review opinion, the company decided to terminate the Phase II INTR@PID BTC 055 study because it is unlikely to reach the primary end point of OS
.
This study aims to evaluate the efficacy and safety of the TGF-β/PD-L1 bifunctional fusion protein bintrafuspalfa (M7824) combined with gemcitabine and cisplatin in the first-line treatment of locally advanced or metastatic biliary tract cancer (BTC).
No new findings were found in this study.
Safety signal
.

bintrafuspalfa structure

Comment: This is the second failure of M7824 in the indications of biliary tract cancer, and it also announced that all the exploration of M7824 in biliary tract cancer ended in failure
.
In addition, this is also the fourth failed study of M7824 this year.
It is regrettable that its head-to-head study with Merck’s PD-1 antibody Keytruda failed
.
However, the failure of combined chemotherapy to show efficacy is thought-provoking, whether it is a mechanism problem or a drug problem
.

It is worth mentioning that in addition to cholangiocarcinoma and lung cancer, M7824 is still exploring the therapeutic effects of cervical cancer, urothelial cancer and breast cancer
.

9.
Kymriah in the treatment of B-cell non-Hodgkin's lymphoma phase Ⅲ study

On August 24, Novartis announced the results of the Phase III BELINDA study of Kymriah (tisagenlecleucel) in aggressive B-cell non-Hodgkin lymphoma (NHL) that has relapsed or progressed in first-line treatment
.
Compared with standard of care (SOC), the Kymriah treatment group did not reach the primary endpoint of event-free survival (EFS)
.

Comment: Kymriah is the world's first CAR-T therapy.
It was approved for marketing in 2017.
It is currently approved for B-cell acute lymphoblastic leukemia that is refractory or at least relapsed after receiving second-line regimens, and for relapse after receiving second-line and above treatments.
/Refractory diffuse large B-cell lymphoma
.
The results of the BELINDA study marked the disillusionment of Kymriah's hopes of advancement of the treatment line
.
However, Kymriah’s two CD19 CAR-T competitors, Gilead’s Yescarta and Bristol-Myers Squibb’s Breyanzi, have recently achieved positive results in the same second-line lymphoma
.

As the first CART drug to be marketed, Kymriah has been suppressed by Yescarta and has never had an advantage in market sales
.
In the first half of 2021, Yescarta still leads the CD19 CAR-T field with sales of 338 million U.
S.
dollars
.

10.
Phase Ⅲ study of JTA-004 in the treatment of osteoarthritis

On August 30, Bone Therapeutics announced that the Phase III study of JTA-004 for the treatment of osteoarthritis failed to meet the primary and key secondary endpoints
.
Affected by this news, Bone's stock price fell more than 34%
.

Bone pipeline products (Source: Bone website)

JTA-004 is composed of plasma protein, hyaluronic acid (a natural component of knee synovial fluid) and a quick-acting analgesic, designed to provide extra lubrication and protection for arthritis articular cartilage and reduce the pain of osteoarthritis
.
Previously, in a phase II study involving 164 patients, JTA-004 showed better pain at 3 and 6 months compared with Hylan GF 20 (Synvisc), the global market leader in osteoarthritis treatment.
Ease
.

In this placebo-controlled Phase III study, the primary endpoint was the efficacy of relieving osteoarthritis and knee joint pain after 3 months based on the WOMAC score scale
.
The results of the study showed that JTA-004 failed to prove a statistically significant difference in pain relief compared with placebo and control drugs
.

Reference materials:

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