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  1. Analysis
June 7, 2022

Pipeline Moves: Eledon’s advancement shot in ALS reviewed after Phase IIa data reveal

The Clinical Trials Arena team also dig into benign tumours, hepatitis B, lymphomas, myelofibrosis, polycythemia vera, and soft tissue sarcoma.

By Clinical Trials Arena Team

In this week’s edition of Pipeline Moves, the Clinical Trials Arena team review the likelihood of further study of Eledon Pharmaceuticals’s Phase IIa amyotrophic lateral sclerosis (ALS) asset tegoprubart, as well as Bristol-Myers Squibb’s relatlimab in lymphomas. The team also dive into the approval chances of SpringWorks Therapeutics’s nirogacestat in soft tissue sarcoma and benign tumours on the heels of Phase III data.

There is also a revisit of Ascentage Pharma’s pelcitoclax, this time in myelofibrosis and polycythemia vera, due to a recent company decision surrounding a Phase I/IIb trial. We also review Antios Therapeutics in hepatitis B now that a Phase II ATI-2173 study was terminated.

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Eledon’s ALS asset likely to advance

Eledon’s tegoprubart for ALS saw its Phase Transition Success Rate (PTSR) jump 16 points to 61% after the company reported positive Phase IIa data. Eledon reported topline data in a May 31 press release, and the PTSR change took effect June 1. PTSR is the probability, given as a percentage, of a drug progressing successfully from one development stage to the next.

The 54-patient Phase IIa trial (NCT04322149) assessed the safety and tolerability of multiple ascending doses of tegoprubart, also known as AT-1501. Tegoprubart met its primary endpoint of safety and tolerability with no reported drug-related adverse events, per the company press release. The trial also demonstrated dose-dependent target engagement and signs of pro-inflammatory biomarkers. Tegoprubart is a monoclonal antibody that inhibits the CD40 ligand, a protein associated with immune response and neuroinflammation in ALS.

Nirogacestat’s approval shot jumps

SpringWorks’snirogacestat saw its Likelihood of Approval (LoA) increase in soft tissue sarcoma and benign tumours after hitting the primary endpoint of a Phase III trial. The LoA rose 12 points to 43% in soft tissue sarcoma and 11 points to 37% in benign tumours.

Phase III DeFi trial (NCT03785964) data was revealed on May 24 via a media release, with the asset’s LoA appraisal occurring May 27. LoA is identified via GlobalData’s analysis using a combination of machine learning and its proprietary algorithm and can be calculated by considering characteristics like therapy area, indication and molecule type.

The 142-patient DeFi trial was designed to target desmoid tumours. They are rare, locally invasive tumours of the soft tissue that do not go through metastasis but have a high risk of recurrence. Nirogacestat demonstrated a statistically significant 71% improvement in DeFi’s primary endpoint of progression-free survival (PFS) compared to placebo (p<0.001). It also reached statistical significance in all key secondary endpoints, including overall response rate (ORR) and patient reported outcomes (PROs).

SpringWorks has said it will present additional data at a medical conference and file an NDA for nirogracestat in H2 2022. Nirogacestat is a small molecule that inhibits gamma secretase, which is implicated in activating pathways associated with desmoid tumour growth.

Opdualag data in lymphoma revealed

Bristol-Myers Squibb’s relatlimab saw its PTSR in Hodgkin lymphoma and non-Hodgkin lymphoma increase after the completion of a Phase I/IIa trial. The PTSR grew by eight points to 34% in Hodgkin lymphoma and by six points to 41% in non-Hodgkin lymphoma.

Relatlimab, as a part of the Opdualag combination approach with BMS’s own Opdivo (nivolumab), secured an FDA approval on March 18 in unresectable or metastatic melanoma. Opdualag was deemed as a step forward in the checkpoint inhibitor space as relatlimab’s anti-LAG-3 mechanism may open the door to a new approach. In fact, this news service reported on March 23 that future first-line melanoma clinical trial designs may have to adjust accordingly.

The 90-subject Phase I/IIa hematologic neoplasm trial (NCT02061761) was updated as completed in a May 26 update on ClinicalTrials.gov, and the PTSR updated by GlobalData the next day. The trial was designed to investigate relatlimab as a monotherapy or in combination with Opdivo. The Phase I/IIa has a variety of coprimary endpoints, covering adverse events, laboratory values and response rates.

Phase Ib/II pelcitoclax trial withdrawn

Ascentage’s APG-1252 (pelcitoclax) saw a slump in its Phase Transition Success Rate (PTSR) in three different indications after the Suzhou, China-headquartered company decided to withdraw a Phase Ib/II study. The PTSR plunged by 15 points to 20% in myelofibrosis. It also dropped by 12 points in both post-essential thrombocythemia myelofibrosis and polycythemia vera, falling to 35% and 24%, respectively.

As per a 2 June update, the Phase I/IIb trial’s (NCT04354727) ClinicalTrials.gov page shows its status changed to “withdrawn”, as well as the study not recruiting any participants. GlobalData appraised the asset a day later.

The study sought to evaluate pelcitoclax in myelofibrosis patients previously treated with Incyte’s Jakafi (ruxolitinib phosphate). The trial tested the asset as a monotherapy, as well as in combination with Jakafi. It has coprimary endpoints looking into toxicity and reduction in spleen volume.

Ascentage’s website lists 11 different assets as part of its pipeline, such as for oncology and hepatitis B. The company is at this year’s ASCO to present updated results from studies in five different assets, including pelcitoclax and olverembatinib. Olverembatinib is approved in China for myeloid leukemia (CML). On May 31, this news service reported pelcitoclax’s decline in advancement chances in small-cell lung cancer after the termination of a Phase Ib/II study.

Antios terminates hepatitis B trial

Antios’s ATI-2173 for hepatitis B saw its PTSR drop nine points to 23% after its Phase II trial was terminated. Antios terminated the trial due to partner collaboration ending, according to a May 31 update to ClinicalTrials.gov. GlobalData updated the PTSR on June 1.

Atlanta, Georgia-based Antios designed the Phase II trial (NCT05238844) to test the safety and efficacy of ATI-2173 and Assembly Biosciences’s vebicorvir in combination with Gilead Sciences’s Viread (tenofovir disoproxil fumarate). There were seven listed primary endpoints, including measures of adverse events, dose-limiting toxicities, and laboratory vital signs. The trial had an anticipated enrollment of ten volunteers with chronic hepatitis B, but only accrued two prior to the study’s termination, according to the trial’s listing.

ATI-2173 inhibits DNA polymerase, which can prevent the replication and spread of the hepatitis B virus. Vebicorvir exhibits antiviral activity by targeting the viral capsid protein. Viread is FDA-approved to treat chronic hepatitis B, and HIV in combination with other antiretroviral agents. 

Need to Know:

GlobalData’s proprietary model uses a combination of machine learning and an algorithm to calculate an individual drug’s PTSR. PTSR indicates the probability of a drug’s advancement to the next stage of clinical development. The model uses data points from the individual drugs, clinical trials, regulatory milestones, company, and financial databases.

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