MS drug development poses a big challenge for pharma

Despite failing some parts of clinical trials, Sanofi to still file for FDA approval

D&D Pharmatech receives the Phase 2 trial approval in the United States…AprilBio jumps into development

Pharmaceutical companies based in South Korea and overseas are having difficulties developing new drugs for multiple sclerosis.

 

Sanofi failed to demonstrate the drug's efficacy in some parts of clinical trials, and Merck's Phase 3 clinical trial did not meet primary endpoints.

 

However, Sanofi announced that it will attempt to receive approval from the U.S.

 

Food and Drug Administration (FDA) since the company acquired results confirming the efficacy in some parts of the clinical trial.

 

In South Korea, D&D Pharmatech and AprilBIO jump into drug development.

 

Sanofi fails to meet the primary endpoints in some of the Phase 3 clinical trials

According to industry sources on September 7th, Sanofi recently completed clinical trials for 'tolebrutinib,' a new drug candidate for multiple sclerosis, and announced that the company will still plan to file for FDA approval.

 

Tolebrutinib is an oral Bruton tyrosine kinase (BTK) inhibitor that works by selectively inhibiting immune responses in multiple sclerosis by regulating B lymphocytes and disease-related microglia.

 

Sanofi acquired the U.S.-based biotechnology company Principia Biopharma for US$3.7 billion (about KRW 4.95 trillion) in 2021 and secured the development rights for Tolebrutinib.

 

Multiple sclerosis is a chronic disease in which the myelin sheaths are damaged due to autoimmune inflammatory responses.

 

Damages to the myelin sheaths cause muscle weakening, fatigue, and vision impairment, and the disease could lead to atraumatic disorders.

 

As of 2022, there are approximately 2674 patients with multiple sclerosis in South Korea, and people aged 20-40 account for 62% of all patients.

 

Until now, antibody medications such as Tysabri (natalizumab), Gilenya (fingolimod), and Mabthera (rituximab) have been used for treating multiple sclerosis.

 

However, there are ongoing requests for new drugs.

 

Sanofi confirmed the efficacy of tolebrutinib through the Phase 3 'HERCULES' study, which involved patients with nonrelapsing secondary progressive multiple sclerosis (nrSPMS).

 

The results showed that tolebrutinib shortened the time to reach confirmed disability progression (CDP), which has been used as the primary endpoint, compared to the placebo group.

 

However, GEMINI 1 and 2 of the Phase 3 trials, which involved patients with relapsing multiple sclerosis, failed to demonstrate the efficacy of tolebrutinib.

 

In these clinical trials, tolebrutinib failed to reduce the annualized relapse rate (ARR) compared to Aubagio (teriflunomide).

 

Notably, tolebrutinib delayed the time till relapse when the secondary primary endpoints were analyzed.

 

Although GEMINI clinical trial results did not meet the primary endpoint, Sanofi plans to file for FDA approval since it secured positive results from the HERCULES study.

 

In South Korea, D&D Pharmatech and AprilBio jump into the field

D&D Pharmatech recently received the Investigational New Drug (IND) approval for the Phase 2 clinical trials of its 'NLY01,' a new drug candidate for multiple sclerosis.

 

NLY01 is a GLP-1 (glucagon-like peptide 1) receptor agonist that works by inhibiting neuroinflammation, which is known as the major cause of degenerative brain diseases and protecting neurons.

 

The NLY01 Phase 2 trial results for Parkinson's Disease were disclosed in 2020.

 

However, 36 weeks of NLY01 administration, which was set as the primary endpoint, did not show statistically significant improvement in symptom alleviation compared to the placebo group.

 

In detail, at 24 weeks of administration, a significant difference was found between the NLY01 treatment group and the placebo group.

 

However, between 24 and 36 weeks, the placebo group’s symptoms showed more improvements than those of the NLY01 group.

 

Then, D&D Pharmatech changed the clinical plan of NLY01 as a new drug for multiple sclerosis.

 

As NLY01 showed effects in regulating neuroinflammation in patients aged 60 years and below in the Parkinson's Disease clinical trial, D&D Pharmatech plans to investigate the candidate's potential as a new drug for multiple sclerosis.

 

The ongoing Phase 2 clinical trial evaluates whether NLY01 reduces neurodegeneration-related imaging indexes in patients with multiple sclerosis.

 

The primary endpoints include changes to the normalization of cerebral volumes.

 

AprilBio has expanded the clinical indication of 'APB-A1,' a new drug candidate for immune disease, to multiple sclerosis.

 

During a conference call, AprilBio's U.S.-based partnering company, Lundbeck, announced that it would expand the APB-A1 development plan to include multiple sclerosis in addition to thyroid eye disease (TED).

 

In 2021, AprilBio out-licensed APB-A1 to Danish pharmaceutical company Lundbeck for US$448 million (approximately KRW 540 billion).

 

APB-A1 is a new drug candidate that inhibits CD40L.

 

CD40L is commonly found in activated T cells following inflammation.

 

Large quantities of cytokines are released when T Cells’ CD40L binds to CD40 of natural killer cells.

 

APB-A1 works by targeting CD40, inhibiting the formation of cytokine-releasing antibodies through B cells and natural killer cells.

 

Now, UCB’s dapirolizumab and the U.S.

 

biotech company Horizon Therapeutics’ Dazodalibep are under development with mechanisms of action similar to APB-A1.