Challenges in access to novel IgA nephropathy therapeutics in South Asia

Summary

IgA nephropathy (IgAN) is a major cause of chronic kidney disease in South Asia, particularly among young adults. Although recent therapeutic advances have transformed IgAN management globally, access to these treatments in South Asia remains limited. Most patients continue to rely on supportive care and conventional immunosuppressives, which have limited efficacy and significant adverse effects. Multiple barriers hinder implementation of newer therapies, including shortage of healthcare capacity and specialist nephrology care leading to delayed diagnosis, high treatment costs, limited resources, lack of universal health coverage, regulatory challenges, and underrepresentation of South Asian populations in clinical trials. This viewpoint discusses the current landscape of IgAN management in South Asia and outlines strategies to improve equitable access to novel therapies, including strengthening healthcare infrastructure and workforce, expanding screening and diagnostic capacity, implementing pricing and reimbursement reforms, facilitating clinical trials and local evidence generation, improving disease awareness in the community as well as healthcare professionals, and enhancing stakeholder advocacy and policy engagement.

Background

IgA Nephropathy (IgAN) is a common primary glomerular disease with a notably higher prevalence among Asian population.¹ The disease typically progresses slowly but leads to kidney failure in majority of individuals within a period of 10–20 years from disease onset.² The global incidence of IgAN varies across region and populations ranging from 0.06 per 100,000 in South Africa to 4.2 per 100,000 in Japan, with limited data available from South Asia.¹ This variation probably reflects regional differences in disease burden, screening practices, healthcare access and biopsy uptake. It is considered an important cause of kidney failure in South Asia, particularly among young patients, although epidemiological data remains limited due to absence of nationwide kidney biopsy registries. Proportion of IgAN in primary glomerular diseases in kidney biopsy cohorts varies widely in this region from 4 to 45%, with limited data from Sri Lanka and Bangladesh.3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13 The proportion of kidney failure attributable to IgAN in this region remains uncertain, however, longitudinal studies have shown that about 30–50% of IgAN patients progress to end stage kidney disease within 3–5 years (Supplementary Table S1).14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24

Management of IgAN patients in South Asia, primarily involves supportive care with optimum blood pressure control and renin angiotensin system blockade with angiotensin converting enzyme inhibitors (ACEi)/angiotensin receptor blockers (ARBs). Systemic corticosteroids, has been the first line therapy for persistent proteinuria, even prior to guideline inclusion,^25,26 but carries substantial risk of infections and other adverse effects.^27,28 The TESTING trial which included 15% South Asian patients, has demonstrated efficacy and safety of low-dose steroids.²⁹ Despite limited evidence in slowing disease progression, Mycophenolate mofetil is often prescribed in steroid-resistant or intolerant patients, however it remains costly with notable infection risk.^25,30 Though hydroxychloroquine use has been reported, it is not widely adopted. Ongoing adaptive platform trials evaluating accessible therapies are expected to clarify the role of the currently available treatments.³¹

Globally, management of IgAN is shifting towards more personalised and mechanism-based approaches to improve patient outcomes. Several new therapies targeting immunologic and non-immunologic pathogenetic pathways of IgAN have been recently approved (Table 1) and some are in development reshaping disease mangement.³² Drugs such as sodium glucose cotransporter 2 (SGLT2) inhibitors,^33,34 sparsentan³⁵ and nefecon³⁶ were included in the updated Kidney Disease: Improving Global Outcomes (KDIGO) guidelines²⁵ for patients with progressive disease. Subsequently, atrasentan,³⁷ iptacopan,³⁸ and sibeprenlimab³⁹ have received approval and are likely to be incorporated in the future.

Table 1.

Novel therapies currently approved for IgA nephropathy.

Therapy	Mechanism of action	Key clinical trial(s)	Regulatory status	Availability in South Asia
SGLT2 Inhibitors Dapagliflozin Empagliflozin	Reduce intraglomerular pressure, anti-inflammatory effect, cardio-renal protection	DAPA-CKD, EMPA-KIDNEY	Approved	Available, including generic formulations
Nefecon	Gut-targeted steroid reducing Gd-IgA1 production	NefIgArd (Phase 3)	FDA approved (2023)	Not available
Sparsentan	Dual endothelin and angiotensin II receptor antagonist	PROTECT (Phase 3)	FDA approved (2024)	Not available
Atrasentan	Selective endothelin A receptor antagonist	ALIGN III (Phase 3 interim analysis)	Accelerated FDA approval (2025)	Not available
Iptacopan	Oral complement factor B inhibitor (alternative complement pathway)	APPLAUSE- IgAN (Phase 3)	Accelerated FDA approval (2024)	Not available
Sibeprenlimab	APRIL (A Proliferation-Inducing Ligand) inhibitor	VISIONARY (Phase 3 interim analysis)	Accelerated FDA approval (2025)	Not available

Barring SGLT2 inhibitors, none of the new treatments are currently marketed in South Asia. There are anecdotal reports of some being imported for compassionate use under named patient supply programs. Nefecon, a targeted-release budesonide which reduces steroid related adverse effects like infections may be especially beneficial for South Asian patients, considering the regional infectious disease burden. Ongoing research may further expand treatment options, but future availability of these therapies is also less likely in the region. Thus, despite global advances in IgAN management, little has changed in South Asia, where patients have access to only limited supportive therapies and those with progressive disease continue to rely on conventional immunosuppressive agents. This viewpoint examines key barriers to implementing these advances in South Asia and proposes strategies to improve equitable access and long-term outcomes.

Key challenges to optimal IgA nephropathy management

IgAN is usually diagnosed with incidentally detected hypertension, haematuria, and/or proteinuria. Absence of screening programs and trained primary health care workforce for kidney diseases coupled with paucity of symptoms in initial stage of disease prevents early diagnosis.⁴⁰ Pilot cross-sectional studies in India and Nepal have explored urinary screening to enable earlier detection of glomerular diseases.^41,42 However, the feasibility of scaling such programs in resource-limited settings remain unknown considering challenges in access to kidney biopsy and limited awareness about the condition among primary and secondary healthcare providers. There is also a marked shortage of nephrologists in South Asia, with a median of 1.8 per million population (IQR 1.4–2)⁴³; compared to the global median of 11.8 (IQR 1.8–24.8).⁴⁴ Data regarding nephropathologists, is limited, however, in India, only about 316 nephropathologists (Indian Society of Renal and Transplant Pathology members) are documented for approximately more than 3000 nephrologists which in turn is impacting diagnosis of IgAN.45, 46, 47 These result in presentation of disease at an advanced stage rendering them ineligible for targeted therapies and, in some cases, even kidney biopsy.

Another challenge in access to the new drugs is their prohibitive cost. Barring SGLT2 inhibitors, the cost of the new therapeutics exceeds $100,000 USD annually or per treatment course. The lack of universal healthcare results in substantial financial burden for the patients, making expensive therapies in any disease unaffordable even when available, as demonstrated in cancer patients.⁴⁸ The need for prolonged management in IgAN patients can further increase the cumulative health costs, deepen poverty and widen health disparities.

Despite high kidney disease burden in the region, several new IgAN treatments were approved based on evidence from clinical trials with limited South Asian population representation.⁴⁹ Global trials of nefecon, iptacopan, atacicept, had limited participation from India and Sri Lanka and subgroup analyses for efficacy in this population were mostly unavailable. The Sibeprenlimab trials had substantial participation from this region and interim analysis of its phase 3 trial which included 26% South and Southeast Asian patients indicated efficacy in these populations.³⁹ While guidelines recommend referring IgAN patients with significant disease to clinical trials when available,²⁵ this is challenging in most parts of South Asia. The limited trial infrastructure, lack of priority for novel drug development coupled with absence of large-scale IgAN registry supporting participant recruitment poses severe challenges for generation of regional evidence. This underrepresentation raises concerns about the applicability of trial findings to these populations especially when they have a unique disease phenotype.¹⁸ Though trial participation may gain access to novel therapies, ensuring continued access to these treatments depends on the trial design, sponsor policies, and national regulatory frameworks which are largely inconsistent. Importing drugs through compassionate use programs often involves complex administrative procedures and significant delays, which can result in treatment interruptions and disease relapse. Ultimately trial participants usually revert to locally available care, highlighting a critical gap in equitable access.

Facilitating access to novel therapies in IgA nephrology

A combination of increased healthcare capacity, government policy with respect to regulatory reforms, stakeholder engagement and generation of robust local evidence could be a feasible pathway to broaden access to new therapies in this region.

Introducing urine screening with dipstick testing by community healthcare workers in primary healthcare setting, can facilitate early diagnosis of IgAN and other kidney diseases. This could be built upon similar existing decentralised models for non-communicable diseases and cancer screening which have been successfully embedded in primary healthcare programs in this region.50, 51, 52, 53 Sustained educational campaigns are needed to emphasise the importance of routine urine analysis among young patients with hypertension, and to facilitate timely referral to nephrologists. Strengthening secondary and tertiary healthcare facilities with training initiatives for nephrologists and nephropathologists is essential to improve diagnostic yield and ensure optimal care. International and regional scientific organisations, such as the International Society of Nephrology (ISN), have contributed to capacity-building and training of the nephrology workforce in LMICs, however, substantial gaps remain in workforce distribution and expertise enhancement. Access to specialist care could be improved by leveraging digital telemedicine platforms. Private sector, which is often the main source for advanced care can be effectively harnessed through public–private partnerships and expansion of public health insurance coverage.

Government pricing negotiations with pharmaceutical companies and subsidies can ensure affordability of new therapeutics. Improving public sector procurement through pooled buying, centralised distribution and reduction in value added taxes on new drugs could reduce cost. Implementing strategies such as China's National Reimbursement Drug List (NRDL) policy which defines access to essential medicines through public insurance using price negotiation to achieve substantial cost reductions could also be considered.⁵⁴ Reducing regulatory barriers to facilitate compassionate import of medicines and exemption of imported drugs from customs duties could facilitate access until they are locally available. Mandatory price revisions may enhance affordability but could potentially discourage pharmaceutical companies from marketing in the region.

Expanded coverage of antiviral therapies in LMICs through national programmes has shown successful results, similar mechanisms could be explored for improving access to drugs for IgAN patients.55, 56, 57 Engagement with non-government organisation (NGO) and capitalising on corporate social responsibility could also reduce the financial burden on patients. However, in the absence of a unified insurance coverage and considering the regions’ resource constraints, even negotiated prices may remain unaffordable for a large proportion of patients.

Cost-effectiveness analysis is a critical tool for informing health policy and optimising resource allocation. Programs such as the UK's National Health Service and Australia's Pharmaceutical Benefits Scheme evaluate the clinical and economic value of treatments before granting free or subsidised access to new therapies.^58,59 Novel therapies for IgAN have been demonstrated to offer substantial long-term benefits in a US-based study.⁶⁰ Comprehensive and locally relevant cost–utility analyses comparing these newer agents with more affordable existing treatments is essential to determine their opportunity cost and guide policy reforms in South Asia.

Governments should facilitate unconditional post-trial access to investigational drugs for trial participants and consider negotiating pricing agreements with pharmaceutical companies during the trial approval process. Policy reforms including accelerated pathways and conditional approvals linked to registry-based evidence can shorten time to marketing, easing restriction and reducing bureaucratic hurdles in drug imports could be beneficial till they are not marketed in this region. Instead of focussing solely on newer therapies, it is crucial to evaluate the efficacy of locally available and affordable alternatives through clinical trials, to improve accessible care. In the absence of nefecon, a more affordable generic controlled-release budesonide formulation approved for inflammatory bowel disease has been repurposed for off-label IgAN treatment in India.⁶¹ Local evidence has informed recommendations supporting the use of hydroxychloroquine and MMF among patients in China,²⁵ an approach that underscores the value of context-specific, accessible treatment strategies, which is worth replicating in South Asia.

Improving awareness about kidney disease and IgAN among healthcare providers and patients can positively influence early referral, diagnosis and health-seeking behaviour. As awareness improves among patients and caregivers, their collective advocacy and dialogue with public health systems, insurers, pharmaceutical companies and regulatory bodies can drive policy change to prioritise access, subsidise costs, and fast-track approvals.

Finally, while facilitating access to novel therapies is crucial, their appropriate use, is equally important. It should be guided by clear regulatory frameworks, guidelines and standardised protocols that are actively enforced to minimise variability in prescribing practices. Asymmetry of information between physicians and patients, can lead to suboptimal treatment decisions and indiscriminate use of therapies with heavy cost implications and potential adverse effects. A pertinent example is the lack of effective antibiotic stewardship which often leads to indiscriminate antibiotic use contributing to alarming levels of antimicrobial resistance.⁶² There is an urgent need for responsible prescribing and active patient participation in clinical decision making.

The evolving landscape of treatment for IgAN, transitioning from non-specific immunosuppressives to targeted therapies, is promising. However, for patients in South Asia, therapeutic approach remains largely unchanged and novel therapies remain a distant hope. Improving access will require concerted efforts including strengthening healthcare capacity and capability at all levels, implementing pricing and reimbursement reforms, facilitating regulatory pathways, evaluating locally available therapeutic alternatives and increasing disease awareness and stakeholder advocacy. Until these new treatments become widely accessible and affordable, they are likely to widen existing global inequities among patients in this region compared to those in high-income countries.

Contributors

SS wrote the initial draft of the manuscript; SBB, EW, MRA, DSS reviewed and contributed to the manuscript; SB: conceived and designed the review, wrote and edited the final manuscript. All authors approved the final version before submission.

Data verification

This manuscript is a review and perspective only. No primary data curation and analysis were performed.

Declaration of interests

SB is a site investigator for clinical trials in glomerular diseases for Novartis, Vera Therapeutics, Fourrts, etc. All funding is received by All India Institute of Medical Sciences with no personal involvement. None of the authors have any competing interest.