[Newsmp]

Duodart (GSK), the first fixed-dose combination of dutasteride plus tamsulosin versus blocker plus 5α reductase inhibitor for the treatment of benign prostatic hyperplasia (BPH), has achieved a market share of over 5% in just one year since its release.

BPH affects more than half of men over the age of 50 and can lead to urinary problems such as frequent urination, nocturia, urgency, and hesitancy, which can significantly impact a person's quality of life. If ignored, it may cause serious complications in the bladder or kidneys.

The treatments for (BPH) typically involve the use of alpha-blockers or 5α reductase inhibitors. Alpha-blockers can quickly relieve the urinary symptoms associated with BPH, while 5α reductase inhibitors can fundamentally reduce the size of the prostate, lowering the risk of serious complications such as acute urinary retention.

Accordingly, major global clinical guidelines recommend that patients with moderate to severe BPH accompanied by urinary symptoms, high prostate-specific antigen (PSA) levels, or a large prostate size and therefore at higher risk of complications should be prescribed a combination of alpha-blockers and 5α reductase inhibitors.

In the meantime, the first fixed-dose combination of a 5α reductase inhibitor and an alpha-blocker, Duodart, was launched in Korea in March of last year.

Duodart has been proven to have better symptom improvement and disease progression inhibition compared to monotherapy with 5α reductase inhibitors or alpha-blockers in major clinical trials. Based on these research findings, it was launched globally in 2010 and is currently the leading treatment for prostate hyperplasia.

In South Korea, Duodart was granted approval by the Ministry of Food and Drug Safety in 2021 and was listed on the insurance coverage list in March 2022.

To commemorate the first anniversary of the launch of Duodart in Korea, Newsmp interviewed Juan Manuel Palacios Moreno, GSK's global medical director of urology, who visited Korea to discuss the clinical benefits of Duodart and its plans.

◇Tamsulosin for rapid symptom relief, dutasteride for long-term disease control
BPH becomes more common with age, with 50% of men in their 50s, 60% in their 60s, and 70% in their 70s experiencing BPH.

Due to the rapid aging of the population in Korea, the number of patients with BPH is increasing steeply, surpassing 1.3 million in 2021.

The active ingredient of Duodart, dutasteride (brand name Avodart), a 5α reductase inhibitor, suppresses the progression of BPH by reducing the production of dihydrotestosterone hormone that causes the disease.

However, the improvement of urinary symptoms that impair the quality of life of patients with BPH appears later with 5α reductase inhibitors than with alpha-blockers.

To address this, GSK developed Duodart, a fixed-dose combination drug that combines dutasteride with tamsulosin using an innovative technology called Poly-cap to enhance the benefits of Avodart while addressing its shortcomings.

Moreno commented that "GSK thought that using both a 5α reductase inhibitor and an alpha-blocker in combination would be more clinically effective than using them alone," explaining the rationale behind the development of Duodart.

More specifically, he stated, "If we combine the ingredient that quickly alleviates symptoms (alpha-blockers) with the ingredient that regulates the progression of the disease over a long period of time (5α reductase inhibitors), the clinical effect can only be significant," and explained that "These two selected ingredients are dutasteride and tamsulosin hydrochloride."

Continuing, "Duodart quickly relieves symptoms with tamsulosin hydrochloride, and as dutasteride acts to control the progression of the disease, symptom relief is maintained steadily," emphasizing that "the addition of dutasteride also reduces the long-term risk of complications such as a lower risk of acute urinary retention or surgery, and all of these effects can be obtained in a single capsule.

◇Large-scale clinical trial confirms Duodart's rapid symptom improvementㆍdisease progression suppression effects

Duodart not only combines two active ingredients in one capsule but also proves the synergy between 5α reductase inhibitors and alpha-blockers through extensive clinical trials.

The Korean approval was based on the clinical trial of CombAT (The Combination of Avodart and Tamsulosin), which was conducted on 4,844 patients aged 50 and over with prostate hyperplasia.

CombAT is a multi-center, double-blind, randomized, parallel-group study that compared and evaluated the combination therapy of dutasteride (0.5mg) and tamsulosin (0.4mg) administered once daily for 4 years with monotherapy of dutasteride (0.5mg) or tamsulosin (0.4mg) administered once daily in patients with moderate to severe lower urinary tract symptoms due to BPH and an increased risk of disease progression.

The results of the study showed that the combination therapy of dutasteride and tamsulosin demonstrated a better symptom improvement effect than dutasteride monotherapy at 3 months and tamsulosin monotherapy from 9 months onwards, and this effect was maintained until the targeted fourth year.

In addition, the combination therapy had a lower risk of symptom progression compared to the monotherapy groups for each of the two ingredients, and it was confirmed that the risk of acute urinary retention and related surgery was further reduced compared to the tamsulosin monotherapy group.

The clinical value of dutasteride was also confirmed in the CONDUCT trial, which targeted 742 patients aged 50 and over with moderate BPH who had a risk of disease progression and no treatment experience.

This multi-center, randomized, open-label, parallel-group study evaluated the effects of a fixed-dose combination therapy of dutasteride (0.5mg) and tamsulosin (0.4mg) and tamsulosin monotherapy in terms of symptom improvement and disease progression inhibition over a period of two years in patients who had not experienced symptom improvement after watchful waiting and subsequently received tamsulosin monotherapy.

The study showed that the group treated with a fixed-dose combination of dutasteride and tamsulosin hydrochloride exhibited a faster improvement in International Prostate Symptom Score (IPSS) starting from one month compared to the group treated with tamsulosin monotherapy and continued to show a superior symptom improvement effect for two years.

Regarding clinical progression of the disease, the group that received fixed-dose combination therapy of dutasteride and tamsulosin hydrochloride showed a lower risk of disease progression within 24 months (18%) compared to the group that received watchful waiting followed by tamsulosin monotherapy (29%).

The risk of disease progression in the group receiving fixed-dose combination therapy of dutasteride and tamsulosin was 43.1% lower than in the group receiving tamsulosin monotherapy after watchful waiting.

Regarding this matter, Moreno stated, "The effects we had hoped for during the development of Duodart have been proven through clinical studies," adding, “The medical personnel at the clinical site have experienced and agreed on the clinical effects of Duodart."

"Duodart has been available and in use since 2010 in countries worldwide, including Europe," he said. "In Spain, more than 300,000 patients have been treated with Duodart, and the previous treatments involving separate intake of the two components or commencing treatment with tamsulosin hydrochloride have been widely replaced by Duodart."

He also attributed Duodart's rapid replacement of the existing market to "the fact that it is possible to achieve rapid symptom improvement and long-term disease progression control with a single drug, Duodart," and evaluated that "especially in terms of safety, the market, medical staff, and patients have all been well receptive, and it has been consistently used to this day."

Moreover, he explained that Duodart not only consolidates two ingredients into one capsule but also enhances the low medication adherence of patients with BPH.

In fact, Duodart has been shown to have a statistically significant higher medication adherence rate compared to the free combination therapy of 5α reductase inhibitors and alpha-blockers through real-world data analysis.

Results from the analysis of data from over 140,000 patients with BPH and lower urinary tract symptoms in the IQVIA database in Germany from 2011 to 2017 showed that more than 80% of patients who demonstrated medication adherence (taking the prescribed medication for at least 80% of the expected treatment duration) were found in the Duodart group at 63.1%, compared to 57.8% in the free combination therapy group.

Moreno emphasized that "Medication adherence is a crucial element in treating BPH. As most patients are elderly and have existing issues with taking multiple drugs, reducing medication administration can be a major success."

He continued, "Since medication adherence rates in the treatment of BPH are quite low worldwide, including in Korea, reducing the number of medications prescribed is very important."

 

◇ With over 20 years of accumulated data, Duodart boasts a superior level of evidence
Based on the evidence obtained from various clinical trials evaluating 5α reductase inhibitors and alpha-blockers in combination therapy, including CombAT, the European Association of Urology (EAU) and the American Urological Association (AUA) recommend the use of combination therapy with 5α reductase inhibitors and alpha-blockers from the early stage in patients with moderate to severe BPH.

However, Moreno explains that even though dutasteride is a 5α reductase inhibitor of the same class, it has a different mechanism and there is a disparity in the level of evidence.

He said, "There are dutasteride and finasteride among 5α reductase inhibitors, and depending on the country, there are 4-5 different alpha-blockers to choose from. Global guidelines had to specify in a way that encompasses the ingredients, considering this situation," and he assumed that "It is up to the medical staff to decide which 5α reductase inhibitor and alpha-blocker to use, and theoretically, any combination is possible."

Nevertheless, he underlined that "Duodart possesses a unique advantage in inhibiting both enzymes necessary for the conversion of testosterone to dihydrotestosterone, which is one of the causes of prostate hyperplasia."

Moreover, he explained that "In addition to the mechanistic differences, one thing I want to emphasize is that the level of evidence generated so far is different." He further stated that "GSK has accumulated data for over 20 years on various topics such as the advantages of fixed-dose combination therapy compared to tamsulosin monotherapy or watchful waiting, the impact on sexual function, and differences in efficacy based on the clinical characteristics of patients."

Stating that "medical professionals who practice evidence-based medicine should be able to recognize combinations that have clear clinical evidence," he expressed confidence. “For instance, these pieces of evidence can serve as a guidepost when deciding whether to use dutasteride and tamsulosin or finasteride and doxazosin, and with a little bit of interest in examining clinical research, it is not difficult to determine which combinations have clinical evidence.”

 

◇Duodart provides optimal treatment recommendations through predictive modeling techniques.

In celebration of the first anniversary of the domestic launch of Duodart, Korea GSK recently held the ONEDERFUL Symposium for medical professionals and introduced its major prostate hyperplasia portfolio, including Duodart and Avodart.

Their presentation of post-marketing research findings, particularly on sexual dysfunction and combination therapies, and their use of predictive modeling approaches drew attention.

He stated that "GSK has been working with conviction in the field of BPH from Avodart to Duodart," and added that "currently, GSK is focusing on identifying the most optimal patient group based on the characteristics of fixed-dose combination Duodart."

"Among them, the customized strategy through data prediction modeling techniques is an approach that helps the necessary patients receive optimal treatment in a timely manner, and the visualized results of the very complex analysis are an innovation achieved by GSK," he said. "Through this, medical professionals can easily assess and understand how symptom scores and risks related to acute urinary retention and surgery change for up to four years when patients are treated with single therapy or combination therapy of Dutasteride and Tamsulosin, or placebo, according to their baseline characteristics."

He said that "GSK highly appreciate the successful celebration of Duodart's first anniversary in Korea and are pleased to have been able to overcome several challenges leading up to its release, thus enabling them to provide Korean patients with sufficient clinical benefits of Duodart."

"The Korean GSK dutasteride team is really working hard and given the high expectations of the Korean medical community, there is great anticipation for the future." He added that GSK will do its best to provide clinical benefits of dutasteride to even more patients, just as it has done in the past.