Fabhalta: learnings for successful drug development in rare diseases
Fabhalta (iptacopan) has emerged as a potential game-changer in the treatment landscape for paroxysmal nocturnal hemoglobinuria (PNH). Recently receiving a positive opinion by the CHMP in the European Union and approval in the United States, this novel drug holds immense promise for patients. In this article, we delve into Fabhalta’s journey, exploring key success factors and drawing lessons from Novartis’s strategic approach to drug development. This article is particularly relevant for drug developers focusing on rare diseases with novel technology platforms.
A new treatment option in PNH
Fabhalta secured FDA approval in December 2023, and a positive CHMP opinion in March 2024, marking a significant milestone. As the first oral monotherapy for PNH in adults, inhibiting Factor B, it aims to reduce anemia and the need for blood transfusions. Novartis, the manufacturer of Fabhalta, recognises its blockbuster potential and as a major contributor to its ambitions for growth. Analysts in turn are excited by its launch with some predicting peak sales of over $1B in PNH alone, indicating that even within rare diseases pharma companies can generate promising returns.
Differentiation
What sets Fabhalta apart? Unlike existing treatments, Fabhalta targets complement Factor B, a critical player in PNH pathogenesis. By binding to Factor B, it prevents both intravascular and extravascular haemolysis, effectively controlling the destruction of red blood cells. This unique mechanism, along with its twice daily oral administration, positions Fabhalta as a promising alternative to the established C5 inhibitors such as eculizumab and ravulizumab. Firstly, Fabhalta takes effect upstream from C5 inhibitors in the disease pathway, potentially leading to better prevention of red blood cell destruction. Secondly, some C5 inhibitors are administered as intravenous infusions which are time consuming for patients and require scarce medical resources.
Clinical and Regulatory Pathway
Fabhalta’s clinical development journey is noteworthy. It underwent two phase 3 trials, one a single arm study of 40 patients in the treatment-naive population and the other for patients previously treated with a C5 inhibitor (97 patients randomised to iptacopan or a C5 inhibitor). These trials demonstrated improvements in haemoglobin levels, reduction in transfusion requirements, and decreased fatigue in patients with PNH.
Additionally, Fabhalta received recognition through regulatory agency designations like Orphan Drug status, PRIME and Breakthrough Designation, streamlining its path to approval.
Competition
Competition in PNH drug development is fierce. Fabhalta faces rivals with established market presence as well as new medications in development. Notably, AstraZeneca’s Factor D inhibitor received FDA approval this month for Vodeya (danicopan) as an add-on to ravulizumab or eculizumab. The addition of danicopan may therefore reinforce existing treatment choices and make it difficult for Fabhalta to take market share. Additionally, new C5 inhibitors such as Roche’s sub-cutaneous crovalimab, approved in China last month, as well as others in development that have reduced dosing regimens, threaten to reduce Fabhalta’s differentiating health economic advantages.
Market Access
Fabhalta’s high list price of $550,000 per patient per year poses challenges. Indeed, the Institute for Clinical and Economic Review (ICER) in its recent review of PNH treatments recommends a price approximately 70% below this level based on its own analysis. Limitations in the study designs, such as a lack of a comparator in the treatment naive patient population, are likely to create downward pricing pressure from payers. Novartis will need to navigate these reimbursement hurdles and demonstrate value to payers and patients alike.
Life Cycle Management
Novartis isn’t stopping at PNH. They’ve invested in exploring six additional therapeutic indications for Fabhalta. In particular, they are planning two additional filings later this year for IgAN and C3 glomerulopathy. This forward-thinking approach and extremely well-timed sequence of launches, will help broaden Fabhalta’s impact.
Conclusion
In summary, Fabhalta’s approval heralds a new era in PNH treatment. Novartis’s strategic choices offer valuable lessons for the pharmaceutical industry, emphasising innovation, differentiation, and lifecycle planning. As Fabhalta enters the market, its success will echo far beyond PNH, shaping the future of drug development.
References:
- Fabhalta: Uses, Dosage, Side Effects, Warnings - Drugs.com
- Fabhalta | European Medicines Agency
- Fabhalta: Package Insert - Drugs.com
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Note, the author of this article does not work for Novartis and has received no payment/compensation from this company.
