Manufacturing Drugs for Selected Rare Diseases: Dr Vinod K Paul

Manufacturing Drugs for Selected Rare Diseases: Dr Vinod K Paul

This is a transcribed speech of Dr. Vinod K. Paul, Member of the National Institution for Transforming India (NITI) Aayog, on “Manufacturing Drugs for Selected Rare Diseases.” He delivered this speech at the World Rare Disease Day 2025 conference, organized by the Indian Organisation for Rare Diseases in Vijayawada, Andhra Pradesh, on February 28, 2025. Check the full video here. 

Honorable Minister for Health, Family Welfare, and Medical Education, Government of Andhra Pradesh, Shri Satya Kumar Yadav Ji, my distinguished colleague, Dr. Ramaiah Muthyala Ji, esteemed dignitaries on the dais, invitees, scientists, pediatricians, colleagues, and friends,

I am deeply honored to be connected with you on this World Rare Disease Day 2025. It is a privilege to express my solidarity and full support for your commendable efforts in addressing the challenge of rare diseases in India and beyond. Due to unavoidable circumstances, I am unable to be present in person, but I am grateful to the organizers for providing this virtual platform to engage with you.

As a pediatrician by training, I have had the good fortune of working with NITI Aayog as part of the policy enabler team of the Government of India. I would like to share an important area of work undertaken by the government. Beyond reaffirming our collective commitment to ensuring the highest levels of health, survival, and quality of life for children born with rare diseases, my primary message today is about the initiatives to provide essential drugs for selected rare diseases and pathways to prevent their occurrence in the future.

I will now present an overview of the government’s initiatives on providing drugs for selected rare diseases. One of the pressing concerns has been the exorbitant cost of importing life-saving medications for rare diseases. While treatment and therapies for many rare diseases remain unavailable globally, those that do exist are often unaffordable for families in India.

In collaboration with leading experts, particularly from the pediatric fraternity, we prioritized the treatment of 13 rare disorders. These include:

• Small molecule drug-treatable disorders: Tyrosinemia Type 1, Gaucher’s Disease, Wilson’s Disease, Dravet/Lennox-Gastaut Syndrome-related seizures, Phenylketonuria (PKU), Hyperammonemia, and Cystic Fibrosis.
• Genetic therapy or enzyme replacement therapy-requiring disorders: Spinal Muscular Atrophy, Duchenne Muscular Dystrophy, Achondroplasia, Pompe’s Disease, Mucopolysaccharidosis, and Niemann-Pick Disease.
• Sickle Cell Disease: While not classified as a rare disease, it was included due to its genetic nature and the need for a concerted effort in management.

For the first group of disorders treatable with small molecule drugs, targeted therapeutics were identified:

• Tyrosinemia Type 1 – Capsule Nitisinone
• Gaucher’s Disease – Capsules Eliglustat and Miglustat
• Wilson’s Disease – Capsule Trientine
• Lennox-Gastaut Syndrome – Cannabidiol Oral Solution
• Phenylketonuria – Tablet Sapropterin
• Hyperammonemia – Tablet Sodium Phenyl Butyrate and Tablet Carglumic Acid
• Cystic Fibrosis – Tablet Ivacaftor
• Sickle Cell Disease – Syrup Hydroxyurea

While tablet hydroxyurea was available, the syrup formulation was not readily accessible in India.

Through a systematic effort involving the genetic research community, pharmaceutical industry, and the regulatory authority (CDSCO), we streamlined the approval process. I am pleased to report that four drugs are now approved and available in the Indian market:

1. Nitisinone (Capsules) – for Tyrosinemia Type 1
2. Eliglustat (Capsules) – for Gaucher’s Disease
3. Trientine (Capsules) – for Wilson’s Disease
4. Cannabidiol (Oral Solution) – for Lennox-Gastaut Syndrome or Dravet Syndrome

The remaining five drugs—Sapropterin, Sodium Phenyl Butyrate, Carglumic Acid, Miglustat, and Ivacaftor—are under process, with significant progress made on Miglustat, which is expected to receive FDA approval within the next few months, followed by Indian regulatory approval later this year.

A key achievement of manufacturing these drugs in India is the significant reduction in costs, making treatment accessible to more patients. For example:

• Nitisinone: Previously priced at ₹2.2 crore ($265,000) annually, the Indian version costs ₹3.7 lakh ($4,500), a cost reduction of nearly 1/60.
• Eliglustat: Originally ₹3.4 crore ($400,000) annually, now available for ₹12 lakh ($15,000), reducing costs by 1/30.
• Trientine: Previously ₹3.2 crore ($385,000) annually, now just ₹3.5 lakh ($4,200), a 1/90 reduction.
• Cannabidiol Oral Solution: Reduced from ₹34 lakh ($41,000) to ₹3 lakh ($3,600), making it 11 times more affordable.

While these drugs are now accessible, the challenge remains in ensuring their widespread availability. Given the limited market demand for rare disease drugs, they cannot be stocked at every pharmacy. Thus, we are exploring alternative distribution models, such as:

1. Centers of Excellence: Ensuring availability through prescription-based channels.
2. Direct Manufacturer Supply: Exploring mechanisms where manufacturers directly supply medications to patients based on authentic prescriptions.
3. Janaushadhi Kendras: Leveraging India’s extensive network of over 15,000 Janaushadhi Kendras, expected to grow to 25,000 soon, to distribute these essential medicines.

Additionally, syrup hydroxyurea, manufactured in India, will be available at an estimated cost of ₹1,500, compared to ₹70,000 for imported versions. This will soon be integrated into the government’s sickle cell disease mission.

India is witnessing remarkable advancements in gene and cell therapy. Notably:

• Indigenous Gene Therapy: In October 2023, India licensed its first indigenous gene therapy for relapsed and refractory B-cell leukemia and lymphomas. Developed by IIT Mumbai and trialed at Tata Memorial Center, this treatment is now available at ₹25 lakh ($30,000), significantly lower than the ₹3.3 crore ($400,000) cost in the US.
• Gene Therapy for Hemophilia A: Recent research published in the New England Journal of Medicine highlights promising trials of lentiviral gene therapy using CD34+ hematopoietic cells.

These breakthroughs inspire confidence that India is poised to develop affordable and advanced therapies for even the most complex rare diseases. The government, scientific community, and industry stakeholders are collaborating to establish a Cell and Gene Therapy Mission to drive research, development, and accessibility.

As we commemorate World Rare Disease Day 2025, I reaffirm my commitment to this noble cause. Our collective mission is not only to develop scientific solutions but also to ensure that treatments reach every affected family. I eagerly anticipate the recommendations from this meeting and assure you of my unwavering support in this journey.

Thank you and best wishes for a successful event.