AstraZeneca’s first-quarter results (PDF) put a twist on a fairy tale, telling the lesser-known story of GOLDILOX and the porcupine. The drugmaker axed a cardiovascular disease prospect after wrapping up the phase 2 GOLDILOX trial while stopping work on early-stage assets bought in from Ionis Pharmaceuticals and Redx Pharma.
The drugmaker is locking the three assets away in its tower as part of a strategic portfolio prioritization. MEDI6570, an antibody that blocks ligands to the LOX-1 scavenger receptor, is the most advanced asset affected by the quarterly cull. AstraZeneca took the molecule into a phase 2 trial in 2020 to assess whether it improves outcomes in patients with a history of heart attacks.
Having wrapped the study up in November, AstraZeneca removed the asset from its pipeline Thursday. Earlier studies implicated LOX-1 in all the main stages of the buildup of plaque in arteries, but the clinical data have failed to persuade AstraZeneca that the molecule is a good use of its money.
Aradhana Sarin, chief financial officer at AstraZeneca, discussed the termination on a media conference call, explaining that the action was based on the company’s “internal evaluation” and was “just part of our normal prioritization process.”
AstraZeneca kicked MEDI6570 out alongside two partnered phase 1 programs. The drugmaker picked up the rights to RXC006, a porcupine inhibitor, for fibrotic diseases from Redx for $17 million in near-term payments in 2020. Porcupine is a key enzyme in the Wnt signaling pathway that is implicated in diseases such as idiopathic pulmonary fibrosis. In theory, targeting porcupine could address lung scarring.
To test that theory, AstraZeneca ran four phase 1 clinical trials between 2021 and 2023. The drugmaker has said little publicly about what it learned in the studies but has decided it has seen enough and cut the program from its pipeline.
The third asset to land on the discard pile is AZD7503, an antisense oligonucleotide AstraZeneca was developing with Ionis. AstraZeneca took the molecule through a series of early-phase trials, culminating in the initiation of a study in people with suspected non-cirrhotic nonalcoholic steatohepatitis in 2023. The liver condition is now known as metabolic dysfunction-associated steatohepatitis (MASH).
Ionis designed AZD7503, also known as ION455, to treat MASH by inhibiting production of a protein that is associated with the progression of the condition in mice and humans. Genetic changes in the gene encoding for the protein, HSD17B13, correlate to the occurrence and severity of MASH, but the molecule failed to survive AstraZeneca’s portfolio prioritization.