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Scleroderma
Published in Jason Liebowitz, Philip Seo, David Hellmann, Michael Zeide, Clinical Innovation in Rheumatology, 2023
The safety and efficacy of a lysophosphatidic acid receptor 1 antagonist SAR100842 was studied in patients with diffuse cutaneous SSc in a double-blind, randomized, eight-week, placebo-controlled study followed by a sixteen-week, open-label study extension (105). Thirty-two patients enrolled, with seventeen receiving placebo and fifteen receiving active drug. The primary end point was safety, and it was found to be well tolerated. The secondary exploratory end point of the mRSS at week 8 favored active therapy (–3.57 [4.18] in the SAR100842 group versus –2.76 [4.85] in the placebo group) but was not statistically significant (p=0.46). Currently, there are two RCTs registered to evaluate the safety and efficacy of ROCK-2 inhibition by KD025 (belumosudil) in diffuse cutaneous SSc (NCT04680975 and NCT 03919799).
Budget impact analysis of belumosudil for chronic graft-versus-host disease treatment in the United States
Published in Journal of Medical Economics, 2022
Carlos R. Bachier, Jeffrey R. Skaar, Sumudu Dehipawala, Benjamin Miao, Jonathan Ieyoub, Haya Taitel
Belumosudil is a selective Rho-associated coiled-coil kinase 2 (ROCK2) inhibitor and immunomodulator that is approved for the treatment of cGVHD for adult and pediatric patients 12 years and older after failure of two or more prior lines of systemic therapy (i.e. 3 L/4L+). National Comprehensive Cancer Network (NCCN) guidelines have included belumosudil as a recommended category 2A option for the treatment of patients with steroid refractory cGVHD8. Belumosudil has been well tolerated in clinical trials, with a low incidence of grade ≥3 adverse events (AEs) (including cytopenias and infections), which may lead to increased compliance to treatment and lower absolute costs9,10. A budget impact model was created to estimate the impact of increasing utilization of belumosudil in 3 L/4L + cGVHD using a US national population or individual payer population perspectives.
A critical review of belumosudil in adult and pediatric patients with chronic graft-versus-host disease
Published in Expert Review of Clinical Immunology, 2023
Amandeep Salhotra, Karamjeet Sandhu, James O’Hearn, Haris Ali, Ryotaro Nakamura, Badri G Modi
Approval of belumosudil in patients with cGVHD was based on the phase 2 ROCKstar trial in which high ORR were seen in patients with advanced cGVHD, a third of whom were previously exposed to ruxolitinib and ibrutinib. Belumosudil has a favorable adverse event profile compared to ruxolitinib and ibrutinib, and median duration of response lasting 54 weeks as described above. Thus, belumosudil may be used in patients with advanced cGVHD failing 2 or more prior lines of therapy and durable responses will be anticipated in such patients. All three currently approved drugs (ibrutinib, belumosudil, and ruxolitinib) inhibit distinct pathways in alloreactive T and B cells and have a unique mechanism of action associated with high response rates in patients with cGVHD. Despite these promising results, the majority of responses seen are partial and most patients need additional lines of treatment due to eventual progression of cGVHD symptoms or side effects of treatment. Further research is ongoing to explore pathways targeting unique immune cell subsets, e.g. activated macrophages (CSF1R blocking antibody axitilimab, NCT04710576). Alternative approaches being attempted include infusion of donor derived regulatory T cells (Tregs) with ex vivo expansion in combination with low dose IL-2 (NCT01937468) or ruxolitinib (NCT03683498). Patients with advanced cGVHD continue to have increased morbidity and mortality from this HCT complication; therefore, patients who are expected to be at high risk of development of cGVHD based on known risk factors such as underlying disease, transplant, and donor characteristics should be monitored closely for early signs of cGVHD onset and appropriate treatment instituted at symptom onset. Newer prophylactic strategies such as the use of post-transplant cyclophosphamide, ATG, and abatacept have been successfully used in both myeloablative and reduced intensity settings in large prospective studies and have shown promise in improving GRFS. Additional strategies being developed such as use of engineered grafts with naïve T cell depletion (NCT03802695) or with Treg/Tcon infusion (NCT04013685) have the potential to reduce the burden of cGVHD in the coming years if results remain promising. Based on the successful use of JAK inhibitors in treatment of acute and chronic GVHD, studies are now underway to explore its use in prophylactic settings in the peri-transplant period in matched donor (NCT04859946 and NCT04339101) and haploidentical donor settings (NCT05364762). With implementation of better prophylactic strategies for GVHD prevention and the availability of newer therapeutic agents to treat established cGVHD, it is hoped that the burden of cGVHD will be lower in the near future in allo-HCT recipients.