With limited treatment options, rare diseases continue to be a challenge globally. According to the Observer Research Foundation (ORF), of all cases of rare diseases across the globe, around one-third occur in India.
These diseases are called rare because they affect a small number of people, however, there is no single accepted definition. Studies suggest there are around 6200 rare diseases across the world. Globally, rare diseases affect between 3.5 percent and 5.9 percent of the population.
In India, there are over 450 types of rare diseases. According to the Organization of Rare Diseases in India (ORDI), 1 in 20 Indians is affected by one of the rare diseases. One such rare disease is Pompe disease.
According to Dr Priya S. Kishnani, Dr. Priya S. Kishnani, a distinguished Indian researcher and Chief of the division of Medical Genetics at the Duke University, Pompe disease is a rare neuromuscular genetic disorder that affects the body’s ability to convert glycogen (stored sugar) into energy. This leads to a buildup of glycogen in a cell type in the body called the lysosome which is the garbage disposal system of the body.
Consequently, this build-up of glycogen, primarily affects skeletal and cardiac muscles, including muscles needed for breathing, leading to progressive muscle weakness and respiratory failure.
“Symptoms of Pompe disease result due to the deficiency of a key enzyme called acid alpha-glucosidase and a patient’s presentation varies depending on the amount of residual enzyme that the body can make: infantile-onset, or late onset. These range from severe muscle weakness, heart problems, respiratory problems, developmental delays and death within the first two years of life in babies with infantile Pompe disease. Patients with late-onset Pompe disease can have a more variable presentation, yet is progressive leading to muscle weakness and ultimately requiring the use of a wheelchair and ventilator support. Enzyme replacement therapy (ERT) remains the specialised treatment for Pompe disease, aimed at replacing the missing enzyme and managing symptoms,” Dr. Krishnani told Financial Express.com.
Dr. Kishnani has made some tremendous contributions in the field of rare genetic disorders and it has transformed the landscape of rare disease treatment across many countries, including India.
Pompe disease differs from other rare diseases in that each rare disease usually has different genes that are involved in making that enzyme important for that particular condition.
Similarly, available treatments vary greatly depending on the specific problem, she said.
The scientist also revealed that it is crucial to understand that Pompe disease is one of many rare diseases, each with its own set of complications. “Understanding the unique characteristics of each condition while sharing some similarities is important for accurate diagnosis, management and research progress,” she added.
‘Pompe disease poses a unique challenge in India’
In December last year, Nidhi Shirol, India’s first Pompe disease patient, passed away last month at the age of 24 years after battling the disease. According to a report by Indian Express, she spent the last six years in a semi-comatose state. In 2010, her father Prasanna Shirol started the Organisation for Rare Diseases India (ORDI) which is the first NGO in the country for rare diseases.
Although the data available is limited, Pompe disease poses a unique challenge in the Indian context, Dr. Kishnani revealed.
“While exact number of patients is unclear, based on understanding from NBS, the frequency is 1:20,000. In India, there are approximately 50 -60 patients in India diagnosed with Pompe disease. Firstly, the limited knowledge of health professionals about Pompe disease delays diagnosis, especially for late-onset Pompe disease. Secondly, the high cost and lack of use of tools like genetic testing prevents early and confirmatory diagnosis. Thirdly, ERT is expensive for most families due to lack of government subsidies or insurance. Lastly, access to primary respiratory care, physical therapy, and other supportive services necessary for management of Pompe disease remains limited,” she told Financial Express.com.
According to findings of research conducted on this subject, late-onset Pompe disease can present earlier and with more rapid disease progression in India, emphasizing the need for early intervention.
In India, more focus needs to be laid on raising awareness, improving diagnosis and advocating for affordable treatment along with increasing clinical research focuses on understanding the specific symptoms of Pompe disease in the Indian population, she emphasised.
“However, the silver lining here is that while significant challenges exist, there are ongoing efforts to improve the diagnosis, management, and overall quality of life for individuals with Pompe disease in India,” she added.
She also maintained that more education amongst geneticists and neuromuscular physicians could lead to more clinical suspicion which in turn would lead to more confirmatory testing.
“It is important to recognize that testing for Pompe disease is extremely easy. It requires blood on a dried blood spot paper card which then can be assessed for the enzyme deficiency,” she said.
While there is currently no cure for Pompe disease, there are some treatment options to manage symptoms. Currently, the Enzyme Replacement Therapy (ERT) is a standard treatment for Pompe Disease. Dr. Kishnani has played a crucial role in the development of the ERT and she was the also associated with Nidhi during her battle with Pompe Disease.
“I am very honoured to have had the opportunity to contribute to the development of Enzyme Replacement Therapy (ERT) and to have worked with Nidhi Shirol, India’s first Pompe patient. Nidhi’s path has demonstrated the tenacity of people fighting uncommon diseases, and her death serves as a reminder of the hurdles that exist in the profession. One of the most difficult aspects of diagnosing Pompe disease, especially those with late onset Pompe disease is the variability in the clinical presentation. Pompe disease can appear at any age, with symptoms ranging from mild to severe, frequently causing delays in diagnosis because symptoms are confused for other more common disorders,” she told Financial Express.com.
It is noteworthy that patients often have a long diagnostic odyssey, see multiple specialists, are often misdiagnosed as limb girdle muscle dystrophy, or polymyositis, on average the diagnostic delay is approximately 6 years for those with an adult presentation, and up to 12 years in those with a childhood presentation.
“In the setting of the latter they are often mistaken for spinal muscular atrophy, developmental delay, etcetera. Furthermore, healthcare personnel’s lack of information regarding Pompe disease and considering it in the differential diagnosis delays the appropriate tests being done to confirm the diagnosis. The disease is frequently underdiagnosed or misdiagnosed, resulting in delays in receiving proper treatment and care,” she said.
The actual number of Pompe patients in India is unknown due to underdiagnosis, misdiagnosis, and the absence of a central registry, Dr. Kishnani revealed. “To summarise, while great advances have been made in the diagnosis and treatment of Pompe disease, there are still obstacles that must be addressed. Increased awareness among healthcare practitioners, better access to diagnostic tools, and continued research are critical to improving outcomes for Pompe patients,” she said.
Undertanding Enzyme Replacement Therapy (ERT) for Pompe Disease
Dr. Kishnani explained that ERT for Pompe disease has been a substantial development in managing the disorder. Some of the benefits of ERT include:
- completely changing the clinical course from a once lethal disease to babies living to adulthood;
- reversal of the heart muscle thickness;
- clinical evidence of improvements in motor function, muscle strength, and regaining strength in breathing muscles as well.
The downsides are:
- high expense,
- limited efficacy, and
- lifelong reliance on infusion.
“The development of alternative treatment options for Pompe disease has been difficult for a variety of reasons, including the disease’s complexity, which includes a wide range of symptoms and disease severity, making it impossible to develop a single medication for all patients. Gene therapy is currently in development, yet it has its own hurdles at this time,” she pointed out.
Currently, Sanofi has two FDA-approved therapies for Pompe’s Disease. “While one of Sanofi’s therapies (Myozyme) to treat Pompe has already been available in the market over a decade, the other therapy (Nexviazyme) is being made available to patients in India through our India Charitable Access Program (InCAP),” Raina told Financial Express.com.
He also informed that Sanofi is planning to launch Xenpozyme, the first and only therapy for the treatment of Niemann-Pick disease (ASMD), in India this year.
“Over the last 15 years, we have been working not only towards enhancing awareness of rare diseases, providing free diagnostic support, but also building capacity of the clinicians, and supporting Centres of Excellence (CoEs) in public and private institutions. We started a charitable access program in India over 25 years back and have treated over 300 patients under this program. In 2024, we plan to launch Xenpozyme in India – the first and only therapy for the treatment of Niemann-Pick disease (ASMD). With this launch, Sanofi Specialty Care in India will be treating 5 debilitating rare diseases, offering hope to those who thought they had none,” he informed.
‘We have just started the journey of rare diseases in India’
In India, diagnosing and treating rare diseases presents a multitude of challenges rooted in limited awareness, insufficient diagnostic infrastructure, and constrained access to specialized care.
“Firstly, the general populace and healthcare providers often lack familiarity with the signs and symptoms of rare diseases, resulting in delays in diagnosis or misdiagnosis. Furthermore, the country faces a shortage of advanced diagnostic facilities, particularly in rural areas, where access to specialized tests for rare conditions remains scarce. Even when available, the high costs associated with diagnostic procedures and genetic testing render them unaffordable for many patients, exacerbating the issue of under-diagnosis,” Anil Raina, General Manager – India, Specialty Care, Sanofi told Financial Express.com.
Additionally, a paucity of physicians who can make timely diagnosis, along with inadequate research and data on rare diseases further hinder efforts to understand these conditions and develop effective management strategies, he explained.
To address these challenges, decisive efforts are needed to enhance awareness, expand diagnostic capabilities, improve access to treatment, train more healthcare professionals, and foster collaboration among stakeholders to advance research and innovation in rare disease care in India, he said.
Over the past few years, rare diseases have caught the attention of a growing number of drugs researchers. Raina revealed that the pharmaceutical industry is increasing its focus on developing novel therapies for many rare diseases, and approvals in the US and Europe are accelerating.
“Besides the conventional therapeutic options, gene therapy is being explored and developed for several rare diseases. The major challenges faced by pharmaceutical companies are the limited access opportunities to these drugs, the high cost of developing and manufacturing the drugs and the extremely limited patient population. These ‘orphan’ drugs (how they came to be called ‘Orphan Drugs’) are intended to treat diseases so rare that sponsors are reluctant to develop them under usual marketing conditions. The process from the discovery of a new molecule to its marketing is often a long one, expensive and uncertain,” he told Financial Express.com.
He also said that with the announcement of the NPRD 2021, the Government has taken a giant leap forward to address the needs and challenges of those living with rare disorders in India.
“However, there is much more that can be done. Development of relevant infrastructure, streamlining of procurement at the COEs and sustainable financial aid are steps that if taken, can help patients with the much-needed support they need. Ensuring early diagnosis and timely treatment is the best way to address the struggles people living with rare diseases face,” Raina told Financial Express.com.
The Dr. Kishnani also maintained that there are a lot of things that needs to be done in the space of rare diseases.
“We have just started the journey of rare diseases in India. There is still a long way to go, beginning with a sense of urgency among the designated Centres of Excellence to commence treatment of all eligible patients. What is also needed is a sustained funding mechanism beyond the one-time INR 50 Lakh assistance given by the Ministry of Health and Family Welfare so that patients can reap the benefits of continued ERT and not be left stranded once the initial amount is over,” she said.
She also highlighted that research and innovation in Pompe disease and other rare diseases are fast progressing, thanks to the technological advancements, improved collaboration among researchers, and growing awareness of these conditions.
“While hurdles exist, the future appears extremely bright for the discovery of novel and improved treatments for these disorders,” she added.
