Keralam defends generic SMA drug 

Why in News?

The Keralam government has defended its decision to provide generic risdiplam, marketed by Natco Pharma as Natsmart, to patients with Spinal Muscular Atrophy (SMA). 

It has also expressed its intention to negotiate further price reductions and eventually provide medicines free to all SMA patients.

What is Spinal Muscular Atrophy?

• SMA is a group of inherited neuromuscular disorders characterised by degeneration of motor neurons, causing progressive muscle weakness and wasting.

• Caused by mutations or deletions in the SMN1 gene (Survival Motor Neuron 1) on chromosome 5 (5q SMA). This leaves them unable to make enough Survival Motor Neuron (SMN) protein, causing the nerve cells that control muscles to wither and die.
• Effect on muscles: Loss of motor neurons disrupts nerve signals to muscles, causing weakness and atrophy (muscle death).
• Inheritance: It is usually autosomal recessive, i.e., an affected child inherits an altered gene copy from each parent. Parents carrying one altered copy generally do not have symptoms.

Symptoms, Types and Diagnosis:

(i) Major Manifestations:

• Progressive weakness, especially in the trunk and muscles closer to the body, such as the shoulders and hips. Difficulty achieving motor milestones, standing or walking.
• In severe cases, impaired swallowing, coughing and breathing. Complications arise, such as scoliosis and joint contractures.

(ii) Clinical Spectrum:

• SMA ranges from Type 0, with onset before birth, to Type IV, with adult onset. Type I generally appears before six months, Type II between six and 18 months, and Type III after 18 months.
• Diagnosis is confirmed through genetic testing. Early diagnosis matters because treatment is most beneficial before extensive, irreversible motor-neuron loss. 

Major Treatment Approaches:

1. Risdiplam: Risdiplam is an oral, small-molecule medicine that helps the body use its backup gene (SMN2) to produce functional SMN proteins. 

• Humans have a backup gene called SMN2, but it has a built-in spelling error (a missing piece called exon 7). Because of this error, it mostly produces unstable, useless protein fragments.
• Risdiplam fixes this error and successfully transforms the backup gene into a reliable factory to produce functional SMN protein, keeping motor neurons healthy and preserving muscle strength. Risdiplam requires continued administration.

2. Gene-Replacement Therapy: Zolgensma uses an adeno-associated virus vector (AAV9) to deliver a functional SMN gene copy. It is a single-dose therapy for eligible patients. Its US-approved intravenous indication covers children under two years with specified SMN1 mutations. 

Need for Generic Risdiplam: 

• Natco has announced a price of ₹15,900 per bottle, compared with reported innovator prices exceeding ₹6 lakh per bottle.
• Lower procurement costs can enable governments to support more patients within existing budgets and reduce families’ dependence on fundraising.
• As Risdiplam requires continued use, affordability affects both treatment initiation and continuity. A recurring therapy needs dependable long-term financing.

Generic development demonstrates the role of Indian manufacturers in improving access to specialised medicines, subject to regulatory requirements and applicable patent law.

India’s Policy Framework: 

• National Policy for Rare Diseases, 2021: The policy provides for specialised care through Centres of Excellence, with financial assistance of up to ₹50 lakh per patient for eligible treatment at notified centres.
• Tax and Duty Relief: The government has provided exemptions for specified rare-disease medicines imported for individual use and through Centres of Excellence, subject to applicable conditions. 
• Compulsory Licensing: Under Section 84 of the Patents Act, 1970, an interested person may apply to the Controller after three years from patent grant on grounds including:
  • Unmet reasonable public requirements.
  • Lack of availability at a reasonably affordable price.
  • Failure to work on the patented invention in India.

Affordable generic risdiplam can expand access to SMA treatment. Its public-health benefit will depend on early diagnosis, assured quality, uninterrupted financing and comprehensive care, allowing lower prices to translate into better patient outcomes.

Practice Prelims MCQ: 

Q. Consider the following statements:

1. The common SMN1-related form of SMA usually follows autosomal recessive inheritance.
2. Risdiplam is a gene-replacement therapy that inserts a functional SMN1 gene.

Which of the statements given above are correct?

(a) 1 only
(b) 2 only
(c) Both 1 and2
(d) Neither 1 nor 2 

Answer: (a). Risdiplam does not introduce a replacement gene.

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