Complications of hematopoietic stem cell transplantation are expected to usher in new drugs

Recently, the US FDA accepted Ruxolitinib (Jakafi)'s Supplemental New Drug Application (sNDS) and granted it priority review as a potential treatment for patients with steroid refractory chronic graft-versus-host disease 12 years of age and older select.
It is expected to make an approval response before June 22 this year.

As early as April 2019, Ruxotinib was approved by the FDA for the treatment of steroid-refractory acute graft-versus-host disease (GVHD) adults and children aged 12 years and older.
This is the first and only drug approved by the FDA for the treatment of steroid-refractory GvHD.

▌Chronic graft versus host disease

Hematopoietic stem cell transplantation is currently an important means to cure a variety of malignant blood diseases including leukemia.
Graft versus host disease (GVHD), as a serious complication after allogeneic hematopoietic stem cell transplantation, has gradually increased its incidence in recent years.
rise.

Allogeneic hematopoietic stem cell transplantation is the implantation of one person's hematopoietic stem cells into another person's body, which is equivalent to transplanting another person's immune system at the same time.
If the two parties can live together peacefully, then there will be nothing wrong with each other; if not, they will fight to death and life, causing serious complications-graft-versus-host disease.

Graft versus host disease is mainly divided into acute type and chronic type.
Acute GVHD generally occurs within 100 days after transplantation, while chronic GVHD generally occurs within 100 days after transplantation.

GVHD affects almost every organ system in the body.
The most commonly involved tissues and organs include the skin, oral cavity, liver, gastrointestinal tract, hematopoietic and immune systems.

In addition, GVHD has diverse clinical manifestations, some of which are similar to autoimmune and other immune diseases, such as scleroderma, Sjogren’s syndrome, primary biliary cirrhosis, and chronic immunodeficiency.

The clinical treatment options for chronic GVHD are very limited.
First-line therapy glucocorticoids and calcineurin inhibitors, but the effective rate is only average.
Most patients still need to switch to second-line therapy, which brings a heavy burden to patients and affects their lives.
quality.

▌JAK inhibitor Ruxotinib

Ruxotinib is an oral JAK1/JAK2 tyrosine kinase inhibitor, which was first approved for marketing in the United States in 2011.
At present, the drug has been approved for multiple indications, including primary myelofibrosis, polycythemia vera, etc.

It is worth mentioning that Belumosudil, an oral ROCK2 inhibitor, has also submitted a New Drug Application (NDA) to the FDA for the treatment of patients with chronic graft-versus-host disease.
It is expected to make an approval response on May 30, 2021.

▌Total remission rate is 50%! Help patients "move" the road safely

This sNDA is based on detailed data from a Phase 3 REACH3 study published at the 2020 American Society of Hematology (ASH) annual meeting.
The study aims to compare the efficacy and safety of ruxotinib and the current best available therapy (BAT) in the treatment of patients with chronic GVHD.

Research indicates:

Compared with the best available therapy (BAT), the overall response rate (ORR) achieved by ruxotinib was significantly improved.
At 24 weeks, the ORR of the ruxotinib group was 49.
7%, while the ORR of the BAT group was 25.
6%.

In addition to the primary endpoint ORR, Ruxotinib has shown advantages over BAT in terms of secondary endpoints such as failure-free survival (FFS), symptom improvement, and response duration.

◆ The median FFS of patients in the Ruxotinib treatment group has not yet reached, while it was 5.
7 months in the BAT group;

◆ Compared with the BAT group, the best overall remission rate of Ruxotinib was higher, which was 76.
4% VS 60.
4%;

◆ According to the modified Lee Symptom Score Scale (mLSS), compared with BAT, 24.
2% of patients in the Ruxotinib group achieved clinically meaningful symptom relief, while only 11% in the BAT group;

◆ Ruxotinib did not reach the optimal median duration of overall response, while it was 6.
24 months in the BAT group.

Based on these results, Ruxotinib met all the primary and key secondary endpoints of the REACH3 study.

Graft versus host disease is fatal for patients who need hematopoietic stem cell transplantation, especially those who do not respond to steroids.
It is expected that this innovative JAK inhibitor will be approved for new indications as soon as possible, and will bring new treatment options for chronic GVHD.
(Good doctor)

Reference materials:

https:// style="text-align:justify;text-indent:2em;">

haoeyou.
com/qita/20210226/5930.
html