Approval Granted for Novel RNA Therapy to Reduce Cholesterol Levels by FDA

The Food and Drug Administration (FDA) has approved a groundbreaking cholesterol-lowering drug called Leqvio. This injectable therapy, developed jointly by Alnylam Pharmaceuticals and Novartis, marks a significant milestone in the treatment of high LDL-C (low-density lipoprotein) cholesterol, often referred to as "bad" cholesterol.

Leqvio's mechanism of action is distinct from mRNA-based vaccines, which provide instructions to cells to produce key parts of viruses to train the immune system. Instead, Leqvio's small interfering RNA (siRNA) is designed to reduce the production of a protein from liver cells that regulates LDL-C levels.

The clinical trial data for Leqvio did not definitively answer whether its use leads to fewer cardiovascular events and longer life expectancy. However, the trial involved nearly 3,500 patients with arteriosclerosis and patients with heterozygous familial hypercholesterolemia (HeFH), who were already on the maximum dose of statins they could tolerate.

The average drop in LDL-C levels for Leqvio users after 17 months, compared to the placebo group, was 52%. Patients will receive the first two subcutaneous injections three months apart, then every six months, at a doctor's office.

Leqvio will only be prescribed as an add-on to diet and statin medication for people with arteriosclerosis or HeFH who still have too-high levels of LDL-C. It is important to note that Leqvio will not be recommended for pregnant women.

The Growing Field of siRNA Therapeutics

The approval of Leqvio represents a significant step forward for siRNA therapy, a mechanism that has been previously approved to treat some genetic disorders but is now being used for lowering cholesterol. The siRNA therapeutic field has seen significant growth since the approval of Patisiran (Onpattro) in 2018 for hereditary transthyretin-mediated amyloidosis.

While siRNA offers advantages over traditional small molecule drugs, challenges such as delivery efficiency, stability, immune stimulation, and off-target effects are being addressed through ongoing research and technological advancements. New siRNA therapies are continually being developed and tested across various disease areas, including kidney injury, hemophilia, and chronic eye disorders, although specific Phase III data for these conditions is not yet available.

Other RNA-based therapies, such as antisense oligonucleotides, are also advancing in clinical trials. For example, AHB-137 is being tested for chronic hepatitis B, highlighting the broader advancements in RNA therapeutics.

Potential Adverse Events and Future Developments

Common adverse events associated with Leqvio include joint stiffness, urinary tract infection, diarrhea, bronchitis, and injection site pain. As the field of siRNA therapeutics continues to expand rapidly, monitoring clinical trial databases and industry announcements would provide the most updated information on siRNA-based therapies for specific conditions.

The success of Leqvio, if it occurs, may signal a new frontier of medicine, following in the footsteps of mRNA vaccines. Leqvio is likely to have a much wider patient base, as it targets millions of Americans with arteriosclerosis who are still on statins and have higher-than-healthy levels of LDL-C.

For the latest developments, checking platforms like ClinicalTrials.gov or company press releases would be beneficial. Additionally, professional conferences like the ESC Congress may discuss relevant trials or advancements in the broader field of RNA therapeutics.

Approval Granted for Novel RNA Therapy to Reduce Cholesterol Levels by FDA