Vonjo (pacritinib)

In conclusion, ruxolitinib was the most potent, and selective JAKinib with no relevant effects in JAK2-independent cells. In contrast, fedratinib, pacritinib, and momelotinib inhibited many other kinases and inhibited cell growth by JAK2-unrelated mechanisms at clinically relevant concentrations.

While no JAK inhibitor has demonstrated clear disease-modifying effects in MF, pacritinib's non-myelosuppressive profile, unique activity against IRAK1, and potential anemia benefit via ACVR1 inhibition suggests potential utility as a backbone for future combination strategies. Ongoing and future studies will be critical to further define its role in phenotype-driven MF management.

P1/2, N=160, Recruiting, National Cancer Institute (NCI) | Not yet recruiting --> Recruiting

P2, N=78, Recruiting, Swedish Orphan Biovitrum | Active, not recruiting --> Recruiting

P2, N=27, Recruiting, University of Washington | Not yet recruiting --> Recruiting

P2, N=58, Recruiting, Karyopharm Therapeutics Inc | N=118 --> 58 | Trial primary completion date: Apr 2026 --> Jun 2027

P1/2, N=25, Not yet recruiting, Thomas Jefferson University

P2, N=78, Active, not recruiting, Swedish Orphan Biovitrum | Trial completion date: Aug 2027 --> May 2028 | Trial primary completion date: Aug 2027 --> Dec 2026

Equally, there is a major focus on next generation JAK inhibitors and mutant calreticulin antibodies. There is also increasing conversation around the need for novel endpoints, as the limitations of symptom assessment, in particular, become apparent and candidate biomarkers of disease modification emerge.

P2, N=78, Active, not recruiting, Swedish Orphan Biovitrum | Recruiting --> Active, not recruiting

He was started on JAK inhibitor therapy with pacritinib but clinically declined over the next several days with worsening diffuse pain and pancytopenia...Shortly after, the patient presented to an outside hospital with septic shock, at which point the patient expired. This case illustrates the aggressive nature of the disease, the need for confirmatory testing when diagnosis is suspected and the difficulty in management as the prognosis is poor and requires aggressive treatment that can lead to life-threatening sequelae.