Semaglutide Shows Remarkable Efficacy in Chronic Kidney Disease, Phase III FLOW Trial Stopped Early

Yesterday, the phenomenal drug semaglutide, which has been globally popular under the name "weight-loss injection," made new progress:

Novo Nordisk announced the latest news about semaglutide.Phase Ⅲ Clinical Study FLOW in China,Due to significant efficacy and fully achieving the preset criteria, the trial will be terminated ahead of schedule.

This time, the significant efficacy was not in lowering blood sugar or reducing weight, but in treating kidney disease.——For patients with type 2 diabetes and renal insufficiency, and patients with chronic kidney disease.

Novo Nordisk announced yesterday. Image source:Reference 1

Early Termination? Efficacy Too Good!

Semaglutide belongs to the GLP-1 receptor agonist (GLP-1RA) class of hypoglycemic drugs. GLP-1 is an incretin that promotes insulin secretion in a glucose concentration-dependent manner, inhibits glucagon secretion, lowers blood sugar, and can also delay gastric emptying to suppress appetite.

Semaglutide injection currently has two products, one is administered once a week at doses of 0.25mg, 0.5mg, or 1mg. It was initially developed as a diabetes treatment drug, launched in the U.S. at the end of 2017, and became available in China in April 2021. Within six months, it entered the national medical insurance negotiation directory.

In April 2021, another SemaglutideSemaglutide Injection (Once Weekly, 2.4mg) Finally Approved by the U.S. FDA for the Indication of "Overweight or Obesity" Following Liraglutide, and Subsequently Approved by the EU in the Same Year [2]。

FL mentioned in yesterday's announcementOW, is aMachine, double-blind, parallel-group, placebo-controlled trial of semaglutide injection 1.0mg versus placebo for the treatment of diabetesThe trial was initiated in 2019, conducted across 28 countries, with a total enrollment of 3,534 patients.

The primary objective of the trial is to compare the effect of semaglutide in preventing the progression of renal impairment in patients with type 2 diabetes and chronic kidney disease (CKD), as well as reducing the risk of renal and cardiovascular death in the composite primary endpoint, which consists of the following five components:

Compared with baseline, 1) persistent reduction of eGFR1 ≥50%; 2) persistent eGFR1<15 mL/min/1.73m²; 3) initiation of dialysis or kidney transplantation; 4) renal disease-related death; 5) cardiovascular disease-related death.

Novo Nordisk's Decision to Halt the Renal Outcomes Trial FLOWThe decision was based on the recommendation of an independent Data Monitoring Committee (DMC). After analyzing the interim results of the study, the committee concluded that it met the pre-specified efficacy criteria for early termination of the trial.[1]

Why, upon reaching the predetermined criteria, is it necessary to halt the clinical trial?

Because clinical trials need to maintain clinical equipoise, meaning that the trialists must ensure that the potential benefits or risks for participants are roughly equal in random grouping. For clinical trials involving patients, it is also necessary to ensure that patients receive appropriate treatment.

In order to maximize the benefits and minimize the risks for trial participants, most clinical trials entrust an independent data monitoring committee to conduct real-time analysis of the trial.If the committee finds that the planned interim analysis has achieved the expected efficacy difference, such as when the intervention in the experimental group is clearly superior to that in the control group, the trial can be terminated early.

Because, at this point, the clinical equipoise for the comparative therapy has been broken by the existing data, and if it continues, it would obviously be unfair to patients assigned to the less effective treatment group.

Currently, to protect the integrity of the trial, the data obtained from the trial remains blinded to the company. Novo Nordisk stated that the full results of FLOW will be published in the first half of 2024. [1]。

Blockbuster "Weight Loss Injection": Will It Become the All-Rounder?

Novo Nordisk's 2022 financial report shows,Semaglutide's global sales have reached $10.9 billion, becoming the first GLP-1RA drug to break $10 billion in annual sales.Despite global shortages, lack of approval for weight loss indications, and prescription restrictions to ensure availability for diabetic patients, sales in China still exceeded $20 billion. [4]。

Star ProductSemaglutidePeptides have become a global phenomenon, with demand outstripping supply, and Novo Nordisk has been relentless in exploring their efficacy in other diseases.

On January 16, 2020, the FDA approved semaglutide's cardiovascular indications based on the results of its SUSTAIN 6 Phase III clinical trial.Namely, the approval of semaglutide for patients with type 2 diabetes and established cardiovascular disease to reduce the risk of major adverse cardiovascular events. [5]。

And just two months ago, Novo Nordisk announcedSemaglutide Injection (Once Weekly, 2.4 mg)SELECT Primary results of the cardiovascular outcomes trial,Evaluated the effect of this drug in preventing the risk of major adverse cardiovascular events (MACE) in overweight or obese patients with cardiovascular disease but without diabetes.(Research Details: "Weight Loss Injection" Has New Uses? Long-Term Results Just Announced)

Compared with using placebo, these patients taking the drug for 5 years reduced the risk of MACE by up to 20%. [2]。

In response to this result, Dr. Martin Holst Lange, Executive Vice President of Development at Novo Nordisk, expressed great excitement: "Obesity increases the risk of cardiovascular disease, but among the weight management drugs currently on the market, none have been shown to reduce the risk of heart attack, stroke, or cardiovascular death while promoting weight loss."

Market feedback also reflects the value of this result from another perspective——After the announcement, Novo Nordisk's stock price surged 16% at the opening of the U.S. market, with its market value surpassing $400 billion for the first time.

AboveWhen the results were announced,Novo Nordisk announced that it is expected to apply for regulatory approval in the United States and the European Union within this year to expand the new indications of once-weekly semaglutide injection (2.4 mg). [2]。

Source of the title image: Visual China

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