Roivant Sciences to Discontinue RVT-2001 Development in Myelodysplastic Syndrome


Investigation of RVT-2001 will be discontinued following an insufficient display of benefit in patients with myelodysplastic syndrome.

Matt Gline, chief executive officer of Roivant

Matt Gline, chief executive officer of Roivant

Development of the investigational SF3B1 modulator RVT-2001 (previously H3B-8800) will be discontinued based on findings from an interim analysis of the phase 1/2 Encore-MDS trial (NCT02841540) in patients with myelodysplastic syndrome (MDS), according to an announcement from developer Roivant Sciences.1

“Unfortunately, the data generated in the phase 1/2 study did not meet our bar for progressing,” Matt Gline, chief executive officer of Roivant, said during Tuesday’s investor call. “And so, we’ve decided to discontinue development of RVT-2001 after an interim analysis of that data.”

The company had invested a “reasonable modest low double-digit million-dollar sum” on RVT-2001, Gline added. “I think just sometimes these things don’t work out the way you want scientifically, and so, we’re trying to be efficient in making those decisions.”

Prior to its discontinuation, RVT-2001 was being developed as a potential first-in-class treatment for transfusion-dependent anemia in patients with lower-risk MDS. Roivant licensed the oral small molecule modulator from Eisai in January 2022. The company conducted this 84-patient phase 1 study, showing that RV-2001 did not produce complete or partial responses despite 5 of 15 patients with MDS and missense SF3B1 mutations achieving red blood cell (RBC) transfusion independence with the agent.2

Encore-MDS was a first-in-human, open-label, multicenter trial designed to evaluate the safety, pharmacokinetic and pharmacodynamic activity of RVT-2001 in patients with MDS, acute myeloid leukemia (AML), and chronic myelomonocytic leukemia (CMML).3

To be eligible for enrollment patients had to have received a confirmed diagnosis of MDS, CMML, or AML, meeting specific criteria pertaining to their diagnosis and have an ECOG performance status of 0 to 2 and adequate baseline organ function.

The study was designed with 3 cohorts for dose escalation, dose expansion, and dose optimization.

Patients with AML (n = 38), higher-risk MDS (n = 20), lower-risk MDS (n = 21), and CMML (n = 4) received RVT-2001 in the dose escalation portion.2

In the expansion cohort, patients had to have lower-risk MDS with an SF3B1 missense mutation defined as low or intermediate-1 per International Prognostic Scoring System (IPSS) criteria.3 In the dose optimization cohort patients had to have transfusion-dependent, lower-risk MDS defined as very-low to intermediate risk per Revised IPSS criteria, with an SF3B1 mutation. In both cohorts, patients had to have an absolute neutrophil count of at least 500 mcL and a platelet count above 50,000 mcL.

Patients with lower-risk MDS were required to be naive to hypomethylating agents (HMAs) and lenalidomide (Revlimid) to be eligible for enrollment in the dose optimization cohort.

Patients with higher-risk MDS/CMML had to have been intolerant to HMAs or unresponsive to 4 cycles of treatment with decitabine or 6 cycles of azacitidine or progressed at any point after starting an HMA.

The primary end points of the trial were the number of patients with dose-limiting toxicity and any treatment-emergent adverse effects (AEs) and serious AEs. Secondary end points included the area under the plasma concentration-time curve from time 0 through the last measurable point, maximum observed plasma concentration, time of maximum observed plasma concentration, the rate of RBC transfusion independence and hematologic improvement, objective response rate, duration of response, time to progression, overall survival, and 3- and 6-month mortality rates.


  1. Roivant to shutter MDS-focused ‘vant’ after disappointing phase I/II trial results. News release. BioSpace. February 14, 2024. Accessed February 15, 2024.
  2. Steensma DP, Wermke M, Klimek VM, et al. Phase I first-in-human dose escalation study of the oral SF3B1 modulator H3B-8800 in myeloid neoplasms. Leukemia. 2021;35(12):3542-3550. doi:10.1038/s41375-021-01328-9
  3. A study of H3B-8800 (RVT-2001) in participants with lower risk myelodysplastic syndromes (Encore-MDS). Updated February 14, 2024. Accessed February 15, 2024.

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