A new drug called BI 690517 has demonstrated significant benefits for patients with chronic kidney disease in a recent phase 3 clinical trial. The drug aims to inhibit aldosterone synthase, an enzyme involved in producing the hormone aldosterone which drives kidney damage at high levels.
The trial results suggest BI 690517 could be a game changer in managing chronic kidney disease and delaying dialysis for millions of patients.
Trial demonstrates reduced albuminuria
In the phase 3 trial with over 1,000 participants, BI 690517 met its primary endpoint by significantly reducing urine albumin creatinine ratio (UACR) after 12 weeks of treatment.
UACR indicates the amount of albumin in urine and is an important marker of kidney damage. High levels of albuminuria are associated with faster progression to end-stage kidney disease.
Compared to placebo, patients receiving BI 690517 at either of two doses had a statistically significant absolute reduction in UACR ranging from -22.3% to -28.9% (p<0.001).
Reductions were observed regardless of participant demographics or existing UACR levels. For some context, a 30% lowering of UACR is expected to translate to a 20-30% decreased risk of kidney failure events long-term.
Slowing kidney function decline
In addition to reducing albuminuria, preliminary data suggests BI 690517 may also slow the loss of kidney function over time.
After 36 weeks, the annualized estimated glomerular filtration rate (eGFR) slope was reduced compared to placebo in those with albuminuria levels >300 mg/g at baseline.
Though the trial duration is likely too short to draw definitive conclusions, these early signals align with the drug’s mechanism of action and point to potential long-term benefits on preserving kidney function.
|Absolute Change in UACR at 12 weeks
|Annualized eGFR Slope at 36 weeks
|-3.56 mL/min/1.73 m2
|BI 690517 Low Dose
|-2.27 mL/min/1.73 m2**
|BI 690517 High Dose
|-1.98 mL/min/1.73 m2**
* p<0.001 compared to placebo
** In participants with baseline UACR >300 mg/g. Data considered exploratory.
Targeting aldosterone and fibrosis
Chronic elevation of the hormone aldosterone drives progressive kidney injury through inflammation and fibrosis. Attempts to directly block aldosterone receptors have run into challenges with hyperkalemia (elevated blood potassium).
Instead, BI 690517 aims upstream at aldosterone synthase – the enzyme responsible for catalyzing aldosterone production in the adrenal gland. Animal models have demonstrated this approach reduces circulating aldosterone without risks of hyperkalemia.
By lowering aldosterone, BI 690517 is believed to alleviate downstream processes involved in nephron injury and fibrosis. Researchers suggest aldosterone inhibition could become an important therapeutic strategy alongside RAAS inhibition to maximally slow CKD progression.
Potential game changer for patients
Doctors and researchers describe BI 690517’s trial results as extremely promising for patients with CKD.
“This is one of the biggest breakthroughs we’ve seen in medicine for chronic kidney disease in 20 years,” said Dr. Katherine Tuttle, a nephrologist and study investigator. “This could be game changing.”
Currently, treatment options for CKD focus mainly on controlling risk factors like diabetes and hypertension. However, new approaches directly targeting mechanisms of kidney injury offer hope to further slow progression.
Aldosterone inhibition with BI 690517 would give clinicians an additional tool alongside ACE inhibitors and ARBs. Earlier intervention expanding beyond risk factor management could greatly impact patient outcomes.
Next steps towards approval
While additional kidney endpoint data is still being analyzed, the significant albuminuria reductions already demonstrated by BI 690517 will support regulatory submissions expected next year.
Phase 3 trials specifically in diabetic kidney disease patients are also underway, which will provide further evidence of efficacy across different CKD populations.
If approved, BI 690517 would become the first aldosterone synthase inhibitor for treating chronic kidney disease. Availability is eagerly anticipated given the immense unmet need of the 30 million US adults currently estimated to have CKD.
With no treatments yet proven to fully halt CKD progression, BI 690517 brings optimism for expanding the treatment paradigm to better preserve kidney function and delay progression to end stage renal disease.
The phase 3 results for BI 690517 represent an important milestone in developing new therapies to manage chronic kidney disease and associated complications.
Targeting excess aldosterone production promises benefits not achieved with current standards of care alone. Widespread use of this first-in-class aldosterone synthase inhibitor could significantly impact long-term outcomes once efficacy and safety are confirmed.
For a patient population in dire need of better solutions, BI 690517 offers renewed hope for improving quality of life and avoiding kidney failure through maximally preserving function. Ongoing research will continue investigating the potential of addressing root pathologic processes in CKD beyond controlling risk factors like diabetes and hypertension.
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