Three Developments That Will Irreversibly Shape the Sickle Cell Disease Therapy Market

Investment in R&D is set to deliver much-needed, potentially disease-modifying therapies for people with sickle cell disease (SCD), especially those with severe disease. Severe disease is characterized by frequent emergency room (ER) visits, long hospital stays, chronic pain, and fatigue. A 20-year gap in new treatments (from the 1998 launch of hydroxyurea to the 2017 launch of Emmaus Medical’s Endari [L-glutamine]) left patients, their families, and physicians with few options (i.e., hydroxyurea, bone marrow transplant [BMT], or chronic transfusions with packed red blood cells). However, the dawn of 2020 offers new therapies and promising data on potentially curative gene therapies. Indeed, the next five years stand to reshape the SCD therapy market into one of increased competition and fragmentation and, more importantly, one characterized by more options, more hope, and potentially better outcomes for SCD patients and their families. Three key developments will underlie this market transformation: the launch and uptake of novel therapies, the arrival of the first gene therapies for SCD, and the battle over these treatments’ pricing.

New treatment options: The recent availability of Novartis’s Adakveo (crizanlizumab), Global Blood Therapeutics’ Oxbryta (voxelotor), and Emmaus Medical’s Endari will change the SCD treatment algorithm. Although these products have rather distinct clinical profiles and product labels, they all face the same challenge—i.e., carving out a niche in an underdeveloped market. Promising clinical data alone will not be enough for success in this market. These companies will need to invest heavily in market development, including educating physicians, patients, and payers about their respective products and ensuring that the right infrastructure is in place for patients to be able to access treatment. Our team is actively speaking to patients and physicians regarding their perception and use of these new therapies and how they are impacting medical practice. We are also following clinical, commercial, and regulatory developments to see their respective effects on the development of this therapy market and the ultimate fate of the various SCD therapies.

Possible curative gene therapy: At present, the only known cure for SCD is a BMT from a bone marrow-matched donor (typically an eligible full sibling). Clinicians estimate that less than one-third of SCD patients can find a matched donor, let alone undergo a BMT. The advent of gene therapy offers an alternative to a BMT that does not rely on a donor but instead uses stem cells from the SCD patient’s own blood. SCD is an ideal target for gene therapy, in part, because a single mutation in the HBB gene for the β-globin subunit of hemoglobin is the underlying cause of the disease. One emerging therapy (Bluebird Bio’s BB305) focuses on inserting a fully functional HBB gene into SCD patients’ stem cells. The other five gene therapies in development (see the table below) aim to induce the production of fetal hemoglobin (HbF). HbF is typically produced only during the first 6-12 months of life. However, when present in children and adults, HbF and its oxygen-carrying capacity can overcome defects in adult hemoglobin.

Gene Therapies in Development for Sickle Cell Disease as of April 9, 2020

Pricing and access: The pricing of innovative therapies, especially treatments for niche and rare diseases, is often very high and comes under close scrutiny from a multitude of stakeholders, including patients, policyholders, physicians, and payers. Therapies for SCD are no different. With the annual U.S. list price of Adakveo estimated at $85,000-113,000 and Oxbryta at $110,000, it is no surprise that these drugs have garnered attention regarding their prices. We are in the early days of understanding the dynamics of drug pricing and reimbursement in the U.S. SCD therapy market, but the following steps should be considered.

• Demonstrate that the SCD drug is cost-effective by showing how treatment reduces physician visits, ER visits, and hospitalizations.
• Demonstrate the SCD drug’s positive impact on patients’ and caregivers’ quality of life.
• Establish a national health agreement with the U.S. Department of Health and Human Services (as is the case with Oxbryta).
• Secure Medicaid approval in key states, particularly the 17 states that account for 85% of diagnosed SCD patients. Of note, the Centers for Medicare and Medicaid Services (CMS) is by far the predominant U.S. payer for SCD: approximately 70% of drug-treated SCD patients are covered by Medicaid or Medicare.
• Obtain favorable positioning on commercial plans’ formularies. Commercial plans cover the remaining 30% of drug-treated SCD patients in the United States.