Amnolake (tamibarotene)

Collectively, our results suggest that tamibarotene may elicit detrimental effects in patients with EBA by abolishing the recruitment of Tregs into skin. This warrants great caution when using tamibarotene in patients with EBA and possibly other pemphigoid diseases.

Aside from allogeneic transplantation, the current standard of care approach for higher-risk myelodysplastic syndromes/neoplasms (HR-MDS) remains monotherapy with a hypomethylating agent (HMA) including azacitidine, decitabine, or oral decitabine/cedazuridine...In this review, we discuss lessons learned from the recently reported negative trials of azacitidine in combination with eprenetapopt (APR-246), magrolimab, pevonedistat, sabatolimab, tamibarotene, and venetoclax...Instead, we advocate for using the IWG 2023 response criteria to better capture clinically meaningful benefits in HR-MDS. Lastly, we emphasize the need for the scientific community to access patient-level data and samples from failed phase 3 trials in an efficient and expedited fashion to inform the development of subsequent trials.

Tamibarotene, a synthetic retinoid used in the treatment of acute promyelocytic leukemia, has been reported to induce differentiation in the SH-SY5Y cell line into neurons. Inhibition of the PI3K/Akt signaling pathway using LY294002 resulted in a decreased efficacy of AM80-induced differentiation in SH-SY5Y cells, along with downregulation of neuronal marker expression. These findings suggest that Am80 can effectively promote the differentiation of SH-SY5Y cells into neurons and reduce the proliferation of neuroblastoma cells, which is related to the PI3K/AKT pathway, providing a good model for the study of nervous system diseases.

The use of tamibarotene-based therapy to target RARα as a novel approach in HR-MDS pts with RARA gene overexpression is not a paradigm which can augment response rates beyond HMA monotherapy. Further explorations of alternative approaches, including those with a biomarker, to alter the natural history of this disease are warranted.

P3, N=246, Terminated, Syros Pharmaceuticals | N=550 --> 246 | Trial completion date: Feb 2029 --> Nov 2024 | Recruiting --> Terminated; As per Sponsor decision, the study was terminated.

P2, N=66, Terminated, Syros Pharmaceuticals | N=95 --> 66 | Trial completion date: Apr 2028 --> Aug 2024 | Active, not recruiting --> Terminated | Trial primary completion date: Apr 2028 --> Aug 2024; As per sponsor decision, the study was terminated.

P2, N=95, Active, not recruiting, Syros Pharmaceuticals | Recruiting --> Active, not recruiting

The impact of revumenib on KMT2Ar or NPM1c AML cells was significantly enhanced when combined with tamibarotene, demonstrating synergistic differentiation or apoptosis initiation. These findings propose promising strategies for relapsed/refractory AML patients with defined molecular characteristics.

In August Year X-1, she developed molecular relapse and was started on tamibarotene(Am80). She died of gastrointestinal hemorrhage. This is considered a valuable case for accumulating information on the treatment of CD56-positive APL resistant to ATRA and ATO.

P2, N=95, Recruiting, Syros Pharmaceuticals | Trial completion date: Apr 2024 --> Apr 2028 | Trial primary completion date: Apr 2024 --> Apr 2028

P3, N=550, Recruiting, Syros Pharmaceuticals | Trial primary completion date: Dec 2023 --> Nov 2024

P2, N=155, Completed, Syros Pharmaceuticals | Active, not recruiting --> Completed