Transitioning from treatment to cure

Characterized by defective hemoglobin that causes Red Blood Cells (RBC) to assume a sickle shape, SCD is a rare genetic condition which affects 8M patients globally. Accelerated RBC breakdown leads to anemia, dizziness, and reduced blood flow, causing chronic pain, potential organ damage, and increased mortality risk. Pain levels vary, often resulting in unpredictable vaso-occlusive crises (VOCs) that severely affect a patient’s quality of life.

Until 2023, the only interventions for SCD, such as hydroxyurea or Pfizer’s Oxbryta, were used to manage associated VOCs, pain, and haemolytic anaemia. In addition to these therapies, blood transfusions may also be used to increase the number of “normal RBCs” in circulation and reduce complications. Bone marrow or stem cell transplants could be considered in severe cases.

The FDA’s historic approval of Vertex’s Casgevy (Jan 2024) and Bluebird Bio’s Lyfgenia (Dec 2023), two pioneering gene therapies (GTs) signified a transformative shift for Sickle Cell Disease (SCD) patients. GTs offer the promise of a cure by editing the patient’s DNA to switch on fetal hemoglobin production or deliver a functional hemoglobin gene to outnumber the sickle cell hemoglobin, respectively.

In line with the new generation of GTs, payors recognise the value of curative therapies despite their premium cost (Cost per patient: Casgevy $2M, Lyfgenia $3M vs. $1M-$3M for previously approved GTs in other rare indications). In the US, Vertex reports strong payer interest in Casgevy – with reimbursement policies in place (commercial insurance) or discussions underway (Medicaid).

Drawing inspiration from early movers in gene therapy, innovators must partner with payors and providers to unlock access by:

  • Implementing “outcome-based rebates” (Novartis’ Zolgensma)
  • Exploring “outcome-based annuities” (Bluebird’s Lyfgenia)
  • Setting up “outcome-based prospective cohort pricing” model based on RWE program (Biomarin’s Roctavian)
  • Engaging with the patient pool early to streamline operations (Biomarin screening eligible patients while conducting reimbursement discussions for Roctavian)

However, besides these pricing considerations, access is also limited by the complexities of GT manufacturing and administration, which require specialized medical centers, stem cell transplants, complex supply chains for cell harvesting and reengineering, and extensive patient processing from chemotherapy to post-treatment monitoring, including prolonged hospital stays and follow ups of up to 8-12 months or longer in specific cases.


Dichotomy of cure – Global North vs. Global South

SCD primarily affects populations of African, Hispanic, and South Asian descent, and the highest disease burden is concentrated in central sub-Saharan Africa and India. As such, GTs are inaccessible and unaffordable to 80% of the prevalent SCD population. Both Vertex and Bluebird Bio have acknowledged that these treatments are unlikely to impact patients in India and Africa who have been closely following the development of these two therapies. “A medicine that is so resource intensive as this is may not be appropriate in many places where the amount of resources for health care is more limited,” said Vertex’s chief scientific officer, Dr. David Altshuler. Bluebird Bio’s, Jess Rowlands, said it was “the unfortunate reality” that the infrastructure needed for such gene therapies “does not exist in much of the world.”

The irony is that these regions with limited infrastructure and ability to continuously support patients in managing VOCs and pain crises, are likely to benefit the most from a one-time curative gene therapy for SCD.

This dichotomy in SCD care, wherein patients in affluent nations have access to potentially curative treatments while those in less developed regions rely on symptomatic management, necessitates a multi-faceted approach with tailored patient outreach and community engagement plans. Albeit unfortunate, this gap presents a commercial opportunity for companies developing SCD-specific solutions and digital tools in low-resource settings.

While the Global North has matured from SCD symptom management to finding an effective cure and improving treatment outcomes, the maturity of available and accessible SCD treatment in emerging countries requires a targeted approach to determine the effective levers to improve patient outcomes.


Diagnosis: Catching up with Global North

The Global North has progressed along the maturity curve in this space, with payors and regulatory authorities focusing on improving patient outcomes and increasing access to potentially curative solutions.

However, the Global South continues to grapple with lower-order problems such as:

  • The lack of widespread SCD screening and diagnosis
  • The availability and access to generic Hydroxyurea in resource-constrained geographies
  • Lack of infrastructure and access to blood transfusions and stem cell transplants

Countries in the Global South can benefit from from ongoing efforts and partnerships to improve the situation, including some driven by Pharma, such as:

  • India’s National Sickle Cell Elimination mission, aiming to provide early diagnosis and screening and a national registry to identify and follow SCD patients
  • Novartis’ Africa SCD program providing early diagnosis and interventions as well as funding research initiatives in SCD
  • Pfizer’s SCD awareness efforts, along with the Nigerian Sickle Cell Foundation

With the increase in internet penetration, digital interventions may also offer a step change in symptom management in the Global South. Smartphone-based solutions are designed to improve treatment adherence and enable early interventions (Sanius, SCD Warrior), thus reducing the risk of VOCs. As the ecosystem matures (e.g., wearables to track hemoglobin levels, patient diaries to report pain, track hydroxyurea use or predict VOCs) digital solutions could ultimately converge into a simple one-stop app for SCD patients vs. the fragmentation today.


Treatment: Bridging the gap to standard of care

Patients in the Global South continue to rely on symptom management via small molecule therapeutics, which have a significantly lower pricing and access barrier, such as  Pfizer’s Oxbryta and generic hydroxyurea. In pockets, patients could also benefit from blood transfusion and a small portion of them may be able to afford to travel to large centres and pay out of pocket for bone marrow transplants, further enhancing treatment outcomes. Evidently, existing health infrastructure and affordability constraints in these regions may limit wider access to novel GTs that can provide significantly improved outcomes for these patients.

Governments in the Global South should rethink existing healthcare delivery models while making the most of limited resources. Partnering with innovators and local patient advocacy entities to increase access to SCD treatments could potentially help bridge the gaps in standard of care (SoC) compared to the Global North.

At the same time, Pharma companies developing GTs should also seek opportunities to engage with relevant government, clinical and payer stakeholders in the Global South to introduce early SCD screening in clinical practice and create national registries to identify suitable patients, establishing regional treatment “hubs” with trained personnel and establishing a potential trial network to provide access to GTs – thus enabling a step change in the SCD treatment paradigm.

Other ongoing efforts to address the challenges of the Global South include industry and academic innovators led “grassroot” innovations such as:

  • Novartis and Precision Biosciences’ research-stage program (PBGENE-NVS) targeting in-vivo administration to offset the requirement for stem cell transplants
  • Penn Medicine’s and Children’s Hospital of Philadelphia’s in-vivo gene editing model for blood disorders (preclinical/research stage)

These solutions may offer a streamlined “one-and-done” approach, eliminating the lengthy and expensive chemotherapy precursor needed to administer traditional gene therapies. However, they are in early-stage research and may take considerable time to become clinically and commercially viable.


Unlocking opportunities in Sickle Cell Disease: bridging the global divide

The stark contrast in care between the Global North and South presents a unique opportunity for SCD innovators to reimagine access models. By focusing on early diagnosis, adopting digital solutions, and embracing creative funding models like the Nigerian Cancer Fund, pharmaceutical companies can revolutionize access and care for patients in the Global South. Key strategies include engaging closely with payers, forging robust partnerships with local governments and NGOs, and learning from successful funding and treatment models in other rare diseases. These steps can help bridge the care gap, addressing both immediate and long-term needs in this underserved population while unlocking substantial untapped value and achieving business growth.

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