[Newsmp]

 

Sanofi-Aventis, the global leader in the rare disease treatment market, has received approvals for new therapies in three rare disease fields in 2023 alone.

Among the three new drugs approved in July, Enjaymo (ingredient: sutimlimab) and Xenpozyme (ingredient: olipudase alfa) can be considered as the first-ever treatments for the corresponding diseases.

Even before this, in March, Nexviazyme (ingredient: avalglucosidase alfa) was approved as a treatment for the rare disease Pompe disease, and it became the first biobetter registered in South Korea by showing remarkable efficacy improvements over existing treatments.

Upon taking over as the CEO of global pharmaceutical company Sanofi in late 2019, Paul Hudson made a daring move by reorganizing the specialized rare disease treatment company Genzyme and merging it with Sanofi. Since then, Sanofi's leadership in the realm of rare diseases has strengthened even further.

In light of this, Newsmp interviewed Kim Bo-young, the Head of Sanofi-Aventis Korea Specialty Care Rare Disease Franchise, to hear about the mission and vision of Sanofi's rare disease franchise.

 

 

◇ The core value of Sanofi's Rare Disease Franchise is 'patient-centricity.'
Sanofi's merger with rare disease specialist Genzyme in 2011 allowed the company to expand its reach into rare diseases beyond vaccines and chronic diseases.

Sanofi has maintained the Genzyme brand after the merger in order to continue to develop rare disease treatments and improve brand value and capabilities.

However, Paul Hudson, who took over as CEO in 2019, said, "We need to invest resources in efficient and opportunistic areas," and under the "Play to Win" strategy, he merged independent brands such as Genzyme and Sanofi Pasteur under one brand, Sanofi.

Following this, Genzyme became a part of Sanofi Specialty Care franchise (Rare Disease Franchise) and continued to concentrate on the field of rare diseases with substantial unmet medical demands.

Kim said that the Specialty Care franchise is a major growth driver for Sanofi as a whole. "We currently have a large pipeline in five treatment areas (immune diseases, rare diseases, rare blood diseases, cancer, and multiple sclerosis), and we are focused on specialty diseases that have a high medical need for treatment."

"Sanofi Specialty Care places utmost importance on two aspects related to new product development. Firstly, supplying 'first-in-class therapies' in areas where rare diseases have no existing treatments, creates transformative milestones in the lives of patients. Secondly, developing superior therapies compared to current treatments, offering the market 'best-in-class therapies' that contribute to enhancing the quality of life for patients undergoing treatment," said Kim. "We are highly focused on these aspects and are preparing multiple treatments for rare diseases and rare blood disorders.”

On the surface, it may seem that Sanofi has integrated its rare disease business into one division after the brand integration, however, in other words, the company's mission to help patients who do not have access to treatment has actually been expanded to the entire company.

"The brand integration was not a major change, but rather a way to spread the heritage and strengths of the rare disease franchise to the entire company as the business diversified," Kim added.

"The rare disease franchise's distinctive value lies in 'patient-centricity,' as the company was established with a focus on patients, making them the center of all decisions," Kim emphasized. "We place our reason and purpose for our work in contributing to the betterment of patients' lives through the 'Miracle of Science."

Furthermore, Kim said, “One of the most crucial aspects in Paul Hudson's Play to Win strategy at Sanofi is taking action for the patients. In short, the corporate brand integration into Sanofi is that the unique value of the Rare Disease Franchise has become the central value of Sanofi, beyond Specialty Care."

 

◇ People who are paving the way for the diagnosis and treatment of rare diseases
The origins of Sanofi's Rare Disease Franchise can be traced back to Genzyme, where the research initially centered around enzyme replacement therapies.

Today, although companies are turning to rare diseases as the chronic disease market is saturated, there were not many companies that were interested in rare diseases at that time, as the number of patients was small, and even doctors had a low understanding of the disease.

Nevertheless, Sanofi has focused on the field of rare diseases with the mission that even a small number of rare disease patients should be able to live a healthy life.

"Genzyme, the predecessor of Sanofi's rare disease business unit, was a company that was researching enzyme therapy. After meeting with Brian Berman, a patient with Gaucher disease, Genzyme decided to put all their eggs in one basket and develop a treatment for Gaucher disease," said Kim. "With the desperate efforts of Brian Berman's parents and the hard work of researchers, Genzyme was able to develop the first treatment for Gaucher disease and make it available to patients all over the world."

"This determination and mission to help rare disease patients have continued to be Sanofi's most important spirit to this day. Sanofi has continued to expand its treatment area, starting with Gaucher disease, and has created a historic path for the treatment of lysosomal storage diseases (LSDs) over the past 30 years," Kim added."

“Last year marked the 20th anniversary of Fabrazyme's launch in Korea, and as Sanofi looked back on the collaborative journey with healthcare professionals, we recognized our significant contributions to the lives of patients with Fabry disease. Our efforts in diagnosing, treating, establishing treatment guidelines, and broadening treatment accessibility have filled us with pride as we continue to forge new paths in the field of rare disease diagnosis and treatment.”

 

 

◇Nexviazyme propels Sanofi, the glopbal leader in the LSD field, to a quantum jump
Sanofi's Rare Disease Franchise took its first steps with Gaucher disease, a representative case of Lysosomal Storage Diseases (LSD).

LSDs are rare genetic conditions that result from the progressive buildup of undegraded substances within the lysosomes due to the deficiency or insufficiency of certain enzymes.

Depending on the accumulated metabolic substances that cannot be broken down, various diseases such as Gaucher disease, Mucopolysaccharidosis, Fabry disease, and Pompe disease can occur.

In 1994, Genzyme, the precursor of Sanofi's Rare Disease Division, pioneered the treatment of LSDs with the development of the world's first enzyme replacement therapy, Ceredase (ingredient: alglucerase).

In the following years, Genzyme expanded the application of enzyme replacement therapy to encompass a wide range of LSDs, continually releasing new medicines and offering a newfound life to patients who were previously in the shadows.

Accordingly, Nature Review Drug Discovery ranked Ceredase as the most innovative new drug in the field of genetics in 2013.

"LSD is a progressive disease caused by a deficiency of a specific enzyme in the lysosome. As the patient ages, the disease gets worse and can lead to death if left untreated," Kim explained.

“Sanofi's rare disease franchise started with Gaucher disease, a type of LSD, and expanded its treatment portfolio to include Pompe disease, Fabry disease, and mucopolysaccharidosis,” Kim added. "The LSDs treatment portfolio includes Fabrazyme (ingredient: agalsidase beta) for Fabry disease, Myozyme (ingredient: alglucosidase alfa), and Nexviazyme for Pompe disease, Aldurazyme (ingredient: laronidase) and Elaprase (ingredient: idursulfase) for Mucopolysaccharidosis, along with Ceredelga (ingredient: eliglustat) and Cerezyme (ingredient: imiglucerase) for Gaucher disease."

Sanofi has recently received approval from the Korean Ministry of Food and Drug Safety for Nexviazyme, the second Pompe disease treatment after Myozyme.

Pompe disease is a progressive neuromuscular disorder characterized by the gradual weakening of muscles due to the deficiency or insufficiency of the acid alpha-glucosidase (GAA) enzyme within the cells' lysosomes.

Various symptoms manifest in Pompe disease, including muscle weakness and respiratory-related conditions such as diaphragm weakness, bronchitis, and pneumonia, with respiratory failure being a major cause of mortality in patients with Pompe disease.

Nexviazyme is a new treatment for Pompe disease that is more effective than the first and only approved treatment, Myozyme. Nexviazyme improves GAA activity, which reduces muscle cell damage and improves safety, and it is the first biobetter to be registered in Korea.

"Before Nexviazyme, Pompe disease patients were only able to use Myozyme, which was approved by the FDA in 2006 and Korea in 2012," said Kim. "Nexviazyme is a product that increases the amount of mannose 6-phosphate (M6P), which plays an important role in the cellular uptake of drugs, by about 15 times compared to Myozyme."

"Nexviazyme's main clinical trial, COMET, showed that Nexviazyme's forced vital capacity (FVC) was non-inferior to Myozyme at week 49, with an increase of 2.43%," Kim added. "In the 6-minute walk test, the Nexviazyme group showed an increase in walking distance of approximately 30 meters compared to the Myozyme group, and positive trends were observed in secondary endpoints, including muscle strength, muscle function, and health-related quality of life in the Nexviazyme group."

Moreover, Kim explained, "In Phase 2 clinical trial Mini-COMET, Nexviazyme was found to be safe and effective in 22 infants with infantile-onset Pompe disease (IOPD) who were switched from Myozyme. There were no serious adverse events that required long-term treatment and no deaths or treatment discontinuations. In terms of motor function/biomarkers, most of the participants had impaired motor function at baseline, but GMFM-88 and QMFT total percentage scores were stable or improved after using Nexviazyme, and plasma CK (muscle damage) and urine Hex4 (glycogen accumulation) levels decreased over time from baseline to 25 weeks."

"Nexviazyme was recognized for its clinical improvement and progress in pharmaceutical technology, and was the biobetter in the category of rare drugs to be approved," said Kim. "Biobetters are drugs that have been recognized by the MFDS with improved safety, efficacy, or utility (compliance and convenience) compared to already approved biologic drugs."

Given the progressive nature of Pompe disease, minimizing the long-term impact on organs requires choosing a more effective treatment from the outset. As such, Sanofi is committed to doing everything possible to secure insurance benefit entry for Nexviazyme to fulfill its role.

"LSDs are caused by the absence of an enzyme, which leads to the accumulation of waste products in the cells, causing tissue damage. Early removal of waste products from cells can help to minimize the damage to organs," Kim added. "As organs cannot regenerate once damaged, starting with the most effective treatment from the outset may be the best approach for patients' long-term outlook. Choosing Nexviazyme treatment as the primary option following a Pompe disease diagnosis could be the optimal decision from a prognostic perspective."

"The health authorities are also considering covering Nexviazyme. The government is also working to ensure that patients with rare diseases can receive treatment more quickly, and patients and medical professionals are eagerly awaiting the development of new treatments."

 

 

◇Early treatment with newborn screening is important for LSDs
As lysosomal storage diseases (LSDs) can cause progressive organ damage and ultimately lead to fatality, early diagnosis and treatment are crucial.

However, due to its rarity, even doctors find it challenging to suspect LSDs, and with many conditions showing similar symptoms, there are not many patients who receive timely diagnoses.

"LSDs can be prevented from worsening lung function, walking ability, and endurance, and the quality of life can be improved if patients receive effective treatment," Kim pointed out. "If treated early, patients can live a healthy life throughout their lifetime, but unfortunately, in reality, patients often go through a diagnostic odyssey of 7 to 15 years."

Taiwan and other countries have implemented newborn screening programs to diagnose LSDs early.

However, in South Korea, there have been some differences of opinion regarding the usefulness of newborn screening for LSDs. This is primarily because the number of patients with such disorders is relatively lower than in Taiwan, and even if diagnosed, the availability of treatable conditions is limited.

Sanofi has been working to improve awareness of LSDs in order to help patients receive treatment as early as possible. The company has also been supporting the cost of screening tests for LSDs when they are suspected by medical professionals.

Kim said that the awareness of lysosomal storage diseases among medical professionals has increased significantly since she joined the company in 2014, “Over the past 10 years, many healthcare professionals have worked to raise awareness of the diagnosis and treatment of LSDs, including Pompe disease. As a result, while there may be healthcare professionals who have never met a patient with LSD, there is no healthcare professional who does not know about the disease.”

“However, the reality is that rare diseases are very rare, nonspecific, and have a variety of symptoms, making it difficult to diagnose,” said Kim. "Therefore, supporting screening tests for early detection is a core area of the rare disease franchise.”

For that reason, Kim added, “Most patients experience a diagnostic odyssey that can last up to 15 years. We believe that it is important for these patients to be able to turn their lives around through early diagnosis and treatment. We are implementing a patient support program to lower the barriers to screening for patients. The screening will be conducted under the medical judgment of medical professionals.”

As awareness of lysosomal storage diseases has improved and the number of diseases that can be treated with enzyme replacement therapy has increased, the voices advocating for government support in newborn screening have gained momentum in recent times in Korea.

According to Kim, newborn screening is the fastest way to diagnose patients, “In South Korea, since 2018, infants aged 28 days or younger have been eligible for free health insurance coverage for tests on about 50 congenital metabolic disorders, and the health authorities are currently considering expanding the program.

"As the birth rate continues to decline, it is becoming more important and urgent for children to grow up healthy and free of disabilities. Even if a disease is diagnosed early, it is important to have a treatment. Currently, most LSDs that can be screened for have treatments, therefore, I hope that the expansion of newborn screening coverage will be actively reviewed."

 

◇We are rare, but we are special
Sanofi has recently expanded its portfolio of rare disease treatments by obtaining approval for Enjaymo, a treatment for the rare autoimmune disorder cold agglutinin disease, and Xenpozyme, a treatment for acid sphingomyelinase deficiency (ASMD)

Beyond leadership in LSDs, Sanofi's commitment is to eliminate suffering in patients with other conditions where no treatment exists and to offer improved therapeutic options.

"Sanofi is expanding its focus to other rare diseases, based on its experience, knowledge, and know-how in the development of lysosomal storage disease treatments. The company is committed to continuing to supply the first or better treatments," Kim said. "On March 25, Sanofi received approval from the Korean Ministry of Food and Drug Safety for Xenpozyme. The company is also conducting clinical trials to provide better treatment options for Fabry disease patients, and is developing an oral substrate reduction therapy (SRT) for the treatment of Tay-Sachs disease, which affects the nervous system."

Kim stated that the Specialty Care Franchise is organizing internal events to raise awareness of rare diseases, involving employees, and actively participating in international campaigns to enhance disease awareness, "Moreover, the company is contemplating its role in enhancing treatment accessibility through maintaining relationships with patient communities, which is particularly important in rare diseases."

"The '6-Minute Walk' campaign, a flagship campaign supporting patients with rare diseases, is based on the '6-Minute Walk' test used to measure disease improvement. Sanofi has been running this campaign for nine years and observed a significant participation rate, surpassing one billion steps in just three days," Kim highlighted.

Kim also said that Sanofi has been working with the Songsuk Foundation, which supports the Fabry Korea patient association, to support young Fabry patients through the "Cheer Up Fabry" program. “Through this program, Sanofi is currently conducting a public relations activity to deliver accurate information about Fabry disease in Korea and working with medical professionals to help many other rare disease patients.”

One example is genetic counseling for the families of Fabry disease patients. Once a patient is diagnosed, Sanofi is working on an efficient support plan to identify other family members early and lead them to treatment by understanding their family tree.

"Fabry diseases can cause serious heart or kidney dysfunction, and patients may die from major heart and kidney complications," Kim said.

However, Kim emphasized that "Fabry disease is an X-linked disorder, which means early diagnosis can be achieved through the patient's family pedigree before organ dysfunction occurs. This means that if one family member is diagnosed, it is important to actively inform the surrounding family members so that they can start early diagnosis and treatment."

"In reality, due to the constraints of the medical conditions in South Korea, where medical professionals must complete consultations within a few minutes, it is challenging for the healthcare team to allocate sufficient time for genetic counseling regarding family pedigrees," Kim added. "In addition to activities to improve patient awareness, we are contemplating in various ways what part of support can be provided so that medical staff can smoothly conduct genetic counseling with patients."

Finally, Kim expressed, "'We are rare, but we are special' is the sentence that explains the purpose of our business unit. I want to convey the message that although rare disease patients face challenges due to genetic reasons, early diagnosis, and treatment can transform their lives from being rare to being special."