FDA Grants Orphan Drug Designation to Evorpacept for AML

The FDA has granted an orphan drug designation to evorpacept (ALX148), a next-generation CD47 blocker, for use as a potential therapeutic option for patients with acute myeloid leukemia (AML), according to a news release from the drug developer, ALX Oncology.¹

“Receiving orphan drug designation in AML, and previously in gastric cancer, from the FDA is an important regulatory milestone and reflects the FDA’s recognition of evorpacept’s potential to improve clinical outcomes in patients with these advanced cancers,” Sophia Randolph, MD, PhD, chief medical officer of ALX Oncology, stated in a press release.

“In our ongoing phase 1/2 ASPEN-05 study [NCT04755244],² we are excited to evaluate the combination of evorpacept with venetoclax [Venclexta] and azacitidine in patients with previously untreated AML who are not candidates for intensive induction therapy or with relapsed/refractory AML,” Randolph added.

The study is expected to enroll 97 patients at least 18 years of age with a cytologically or histologically confirmed diagnosis of relapsed/refractory or newly diagnosed AML per World Health Organization 2016 classification with adequate renal and liver function and performance status.

The primary efficacy outcomes in the phase 1 and 2 portions are the number of patients with dose-limiting toxicities and the number of patients achieving a complete remission with incomplete hematologic recovery per European LeukemiaNet 2017 criteria, respectively. 

In June 2022, the company announced that the phase 1 dose-escalation portion of ASPEN-05 had completed enrollment and that no safety concerns had occurred up to the highest protocol defined dose level of 60 mg/kg of evorpacept administered once every four weeks.³

The company added that patient enrollment would be paused before proceeding into the phase 1 dose-optimization portion of ASPEN-05 pending completion of the phase 1 portion of ASPEN-02 (NCT04417517),⁴ a phase 1/2 study evaluating the combination of evorpacept and azacitidine in patients with higher-risk MDS. 

In the phase 1 portion, patients will receive escalating doses of evorpacept in combination with 75 mg/m2 of intravenous (IV) or subcutaneous azacitidine daily for 7 days of a 28-day cycle. In the phase 2 portion, patients will receive evorpacept at the recommended phase 2 dose in combination with 75 mg/m2 of IV or subcutaneous azacitidine daily for 7 days of a 28-day cycle.

Data from ASPEN-02 will be used to inform the optimal dose(s) of evorpacept to be studied in the ASPEN-05 study in combination with venetoclax and azacitidine. Ongoing patients in ASPEN-05 will continue to be treated and followed per protocol.

“The decision to pause ASPEN-05 is based on the desire to leverage upcoming dose optimization data from the ASPEN-02 MDS study to effectively inform dose optimization in ASPEN-05,” Randolph said.3 “MDS and AML are indications where evorpacept possesses a similar mechanism of action, and this strategy allows us to evaluate evorpacept in a cost-efficient manner in patients with AML while maintaining our focus in our solid tumor programs. We anticipate preliminary dose escalation data from ASPEN-05 to be presented at a scientific conference in 2022, and initial dose optimization data from ASPEN-02 to be presented at a scientific conference in mid-2023.”

References

1. ALX Oncology Receives U.S. FDA Orphan Drug Designation for Evorpacept for the Treatment of Patients with Acute Myeloid Leukemia. News release. ALX Oncology. June 29, 2022. Accessed July 1, 2022. https://bit.ly/3ODSsQz
2. A study of evorpacept (ALX148) with venetoclax and azacitidine for acute myeloid leukemia (ASPEN-05). ClinicalTrials.gov. Updated June 9, 2022. Accessed July 1, 2022. https://clinicaltrials.gov/ct2/show/NCT04755244
3. ALX Oncology announces evorpacept clinical program updates. News release. ALX Oncology. June 3, 2022. Accessed July 1, 2022. https://bit.ly/3a4SzFM
4. A study of evorpacept (ALX148) with azacitidine for higher risk myelodysplastic syndrome (ASPEN-02). ClinicalTrials.gov. Updated May 16, 2022. Accessed July 1, 2022. https://clinicaltrials.gov/ct2/show/NCT04417517