What's New?

Karyopharm Therapeutics Inc. has initiated the Phase 2 expansion of a study investigating eltanexor, a novel oral compound, for the treatment of hypomethylating agent (HMA) refractory myelodysplastic syndrome (MDS). The Phase 2 expansion aims to evaluate eltanexor monotherapy's efficacy, with the primary endpoint being overall response rate (ORR). The decision to expand the study follows promising results from the Phase 1 portion, where eltanexor demonstrated a 53% ORR and a median overall survival of 9.9 months in patients with high-risk, relapsed MDS refractory to HMAs. The study includes an additional 83 patients, with the first patient recently dosed. Eltanexor functions by inhibiting the nuclear export protein XPO1, leading to the accumulation of tumor suppressor proteins and selective induction of apoptosis in cancer cells. The drug has shown promising results in preclinical models, suggesting its potential as a cancer therapy. However, eltanexor is still investigational and has not been approved by regulatory agencies.

Geron Corporation updated progress on its IMerge Phase 3 trial for lower-risk myelodysplastic syndromes (MDS) and reported second-quarter financial results. With over 90% enrollment achieved, the trial is expected to be fully enrolled by Q4 2021, with top-line results anticipated by Q1 2023, three months earlier than planned due to an extended follow-up period prompted by the COVID-19 pandemic. Geron plans an investor day in November 2021 to discuss imetelstat's potential, expansion plans, and a discovery program for second-generation telomerase inhibitors. Financially, the company reported a net loss of $29.6 million for Q2, with $239.1 million in cash and marketable securities as of June 30, 2021, expected to fund operations through Q1 2023.

AbbVie's VENCLEXTA® in combination with azacitidine received Breakthrough Therapy Designation (BTD) from the FDA for treating adult patients with previously untreated intermediate- to very high-risk myelodysplastic syndromes (MDS) based on IPSS-R. MDS, characterized by insufficient healthy blood cell production, affects around 10,000 US patients annually, with 30% progressing to acute myeloid leukemia (AML). This marks the sixth BTD granted to venetoclax, reflecting AbbVie's commitment to addressing challenging myeloid malignancies. The designation, supported by Phase 1b M15-531 study data, accelerates medication development for serious conditions. Venetoclax, jointly developed by AbbVie and Roche, targets the B-cell lymphoma-2 (BCL-2) protein, potentially restoring apoptosis in certain blood cancers.

For over 30 years, umbilical cord blood (UCB) has been a crucial source of hematopoietic stem cells for transplantation, particularly for non-white patients who are underrepresented in adult donor registries. However, UCB transplants have higher early treatment-related morbidity and mortality due to delayed hematopoietic recovery. Advances such as dual UCB grafts and better pre-transplant conditioning have improved outcomes, but delays in recovery persist. Early studies show that ex vivo expansion of UCB stem cells can accelerate neutrophil recovery. Omidubicel, a product derived from a single UCB unit and expanded ex vivo with nicotinamide, enhances hematopoietic recovery. A trial comparing omidubicel to standard UCB transplants found that omidubicel significantly reduced the median time to neutrophil recovery from 22 to 12 days, improved platelet engraftment, and decreased infection rates, with no significant increase in graft-versus-host disease.

Jazz Pharmaceuticals announced that the FDA approved Vyxeos® (daunorubicin and cytarabine) for treating newly diagnosed therapy-related acute myeloid leukemia (t-AML) or AML with myelodysplasia-related changes (AML-MRC) in pediatric patients aged one year and older. This approval is based on safety data from two single-arm trials (AAML1421 and CPX-MA-1201) and effectiveness data from an adult study. Vyxeos is now indicated for both adults and children with these forms of AML. Jazz Pharmaceuticals emphasizes the critical need for effective pediatric AML therapies and its commitment to broadening cancer research. The studies demonstrated no age-based safety differences, and Vyxeos' approval marks an important advancement for pediatric leukemia treatment.

AbFero Pharmaceuticals, Inc., a clinical-stage company focusing on iron overload diseases, has begun a Phase 1 study of its lead iron chelator, SP-420, in patients with myelodysplastic syndromes (MDS) and myelofibrosis (MF) suffering from transfusional iron overload (TIO). This trial, conducted by Dr. Elizabeth Bowhay-Carnes at UT Health San Antonio, aims to evaluate SP-420's safety and will lay the groundwork for future efficacy studies. AbFero's CEO, Thomas X. Neenan, emphasized the importance of this trial in advancing SP-420's development. Dr. Ruben Mesa of the Mays Cancer Center highlighted the significance of addressing TIO in patients with chronic leukemia and bone marrow disorders. AbFero's technology, based on Professor Raymond Bergeron's discoveries, targets TIO and iron-related aging diseases like AMD and Parkinson's. The study will provide essential safety data in 2021.

Gamida Cell announced positive results from a Phase 3 study of omidubicel, a potential cell therapy for patients with hematologic malignancies needing a bone marrow transplant. The data, presented at the 2021 TCT Meetings, showed that omidubicel led to faster hematopoietic recovery, fewer infections, and reduced hospitalization compared to standard umbilical cord blood transplants. The study met its primary and secondary endpoints, demonstrating significant improvements in neutrophil and platelet engraftment and lower infection rates. These results will support a Biologics License Application (BLA) submission to the FDA in the second half of 2021.

Medexus Pharmaceuticals has secured exclusive U.S. commercialization rights to treosulfan, an orphan-designated conditioning agent for allogeneic hematopoietic stem cell transplantation (allo-HSCT), through a deal with medac GmbH. Treosulfan, expected to reduce toxicity and improve survival outcomes, has an FDA review date set for August 2021. A Phase III study showed it to be non-inferior to busulfan, the current standard. Medexus plans to launch treosulfan soon after FDA approval, leveraging its U.S. infrastructure. The agreement includes an upfront payment of $5 million, milestone payments, and royalties on net sales.