Novartis Halts Phase II Trial for MIJ821 in Suicidal Major Depressive Disorder, Jeopardizing $770M Cadent Acquisition

On October 9, local time in the United States, pharmaceutical giant Novartis confirmed to the biopharmaceutical industry media Endpoints News that the company has canceled a Phase II clinical trial for the MIJ821 pipeline, which was intended to treat severe depression associated with suicidal ideation.

Novartis spokesperson said in an email that the decision was made "after a benefit-risk assessment of the existing data." The spokesperson added: "The investigators did not find any new or changed safety signals." "We then communicated with the researchers and health authorities, and we continue to be committed to sharing study information with patients and the scientific community to help inform future treatment options for this challenging disease."

MIJ821 Pipeline Originates from Cadent Therapeutics, a Biopharmaceutical Company Focused on Neuroscience. The Company Was Acquired by Novartis in December 2020 for up to $770 Million, Including $210 Million in Upfront Payment and up to $560 Million in Subsequent Milestone Payments. The Termination of the Phase II Clinical Trial of the MIJ821 Pipeline Also Signifies the Collapse of Novartis' $770 Million Acquisition.

Cadent is an innovative technology company dedicated to creating breakthrough therapies for patients with cognitive and motor impairments. The company was established in 2017 after merging with Luc Therapeutics and Ataxion Therapeutics.

But as early as before Cadent was acquired, in 2015, the MIJ821 pipeline had already been licensed to Novartis.

Before being acquired by Novartis, Cadent had completed several rounds of financing, accumulating tens of millions of US dollars. The largest financing occurred in 2018 when Cadent raised 40 million US dollars in its Series B round, gaining favor from several well-known investment institutions including Cowen Healthcare Investments, Atlas Venture, Qiming Venture Partners, Access Industries, Clal Biotechnology Industries, and Novartis Institutes for Biomedical Research.

In that year, Cadent also signed an exclusive licensing and cooperation agreement with Novartis to jointly develop a negative allosteric modulator for the treatment of patients with depression.

Two years later, Novartis announced the acquisition of Cadent, gaining Cadent's complete neuroscience product portfolio, with a focus on the core pipeline CAD9303 and MIJ821.CAD9303 is a positive allosteric modulator of NMDAr for schizophrenia, while MIJ821 is a negative allosteric modulator of NMDAr for the treatment of depression, which can selectively modulate a subset of NMDA receptors associated with depression.

In July 2021, Novartis began a comparative trial of intravenous MIJ821 versus placebo to observe whether MIJ821 could better alleviate depressive symptoms.Previously, Novartis tested different doses of the MIJ821 drug against a placebo and ketamine, stating that MIJ821 "was designed to act like the antidepressant ketamine but with a lower probability of dissociation."

According to the entry on clinicaltrials.gov, the trial involving nearly 200 patients ended in July this year.

But according to the latest information from clinicaltrials.gov, Novartis' another Phase II clinical trial of subcutaneous injection MIJ821 is still recruiting patients with treatment-resistant depression.

Despite the difficulties, Novartis has not abandoned the MIJ821 pipeline, as it is linked to a vast blue ocean market worth billions, involving hundreds of millions of patients.

According to statistics from the World Health Organization (WHO), approximately 1 billion people worldwide are suffering from mental disorders, with over 350 million affected by depression. Following the COVID-19 pandemic, the global burden of mental health disorders has intensified, with cases of major depressive disorder and anxiety disorders increasing by 28% and 26%, respectively. Globally, there are over 70 million new cases of depression and 90 million new cases of anxiety, while hundreds of millions of individuals are experiencing issues such as sleep disorders.

Depression has become the fourth largest disease in the world. According to the "2022 National Depression Blue Paper," there are approximately 95 million patients in China alone. However, the treatment rate for patients in China is severely insufficient, with only 9.5% receiving treatment (compared to nearly 50% in high-income countries), and only 0.5% of patients receiving adequate treatment, showing a significant gap compared to high-income countries.

According to the analysis by Research and Markets, the global antidepressant market was estimated at $14.5 billion in 2022 and is projected to reach $17.6 billion by 2030, with a compound annual growth rate (CAGR) of 2.5% from 2022 to 2030; the size of China's antidepressant drug market was approximately 17.2 billion yuan in 2022 and is expected to reach 23.8 billion yuan by 2030, with a CAGR of 4.2% from 2022 to 2030, growing at a faster rate than the global average.

Despite the urgent clinical needs and the vast pharmaceutical market, curing depression remains a challenge. According to data from Deutsche Securities, the relapse rate of depression is as high as 50%-85%, with 50% of patients experiencing a recurrence within two years after the onset of the disease. Additionally, an article published in The Lancet Psychiatry in 2019 indicated that the lifetime prevalence of depression is 6.9%, while the 12-month prevalence is 3.6%.

The development of depression drugs has both a sufficiently high threshold and a sufficiently broad market space, naturally attracting many companies to actively invest.

International pharmaceutical companies such as Lundbeck, Eli Lilly, Pfizer, Wyeth, Teva, and domestic companies like Kanghong Pharmaceutical, Betta Pharma, Kelun Pharmaceutical, Harbin No.3 Pharmaceutical, Huahai Pharmaceutical, Jingxin Pharmaceutical, Western Point Pharmaceutical, Jianfeng Group, Dongyangguang Pharmaceutical, Guangwei Pharmaceutical, Hansoh Pharmaceutical, Salubris, CSPC, Enhua Pharmaceutical, Luye Pharmaceutical, Huachun Biotech, Yiling Pharmaceutical, and Siji Pharmaceutical have all made strategic moves.

At present, the global antidepressant drug R&D industry is in a flourishing period with a profusion of developments, as pharmaceutical companies are vigorously competing to make breakthroughs.

According to the data statistics from PharmaYun,There are 2,744 depression R&D drugs globally(including active and inactive), of which only 3% are drugs in the IND and above R&D stages, including 37 in clinical Phase I, 38 in clinical Phase II, 4 in clinical Phase III, and 3 applying for marketing approval. The top five popular targets are IDO1, GRIN2B, GABRA1, NMDAR, and SLC6A4.

There are 723 antidepressant drugs under development in China.(including active and inactive), of which only 2% are drugs in the R&D stage above IND, including 9 in clinical Phase I, 4 in clinical Phase II, and 1 application for marketing.

Despite the vigorous development of the industry, among the aforementioned drug developments, there are 155 drugs in a terminated state of research and 405 drugs with no subsequent progress reported, accounting for 20.4% in total.

From this perspective, Novartis' announcement to terminate the Phase II clinical trial of the intravenous MIJ821 pipeline represents a failure that is not uncommon in clinical cases. Despite this setback for Novartis in this pipeline, the company has stated that it will release its latest pipeline on October 24. Let us be patient and look forward to Novartis achieving outstanding results in other areas.

In this "Alexandra" social environment, we inevitably face pressure and negative emotions from all sides. When we can still digest these emotions, perhaps we should learn to be friends with time and learn to be friends with tolerance. When we cannot deal with these emotions in time, we should actively seek help from friends, family, and doctors.

When faced with friends around us who have depression and seek help, we should not simply attribute their condition to "being in a bad mood" or "under too much pressure." Instead, we need to learn to listen and understand.Perhaps, the support and understanding of friends and family can also be a good medicine for treating depression.