Re: The budget impact of enzyme replacement therapy in type 1 gaucher disease in the United States

View addendum:

Re: Response letter to Sanofi’s communication related to “the budget impact of enzyme replacement therapy in type 1 Gaucher disease in the United States”

This article refers to:

The budget impact of enzyme replacement therapy in type 1 Gaucher disease in the United States

Dear Editor,

We read with interest the recently published budget impact analysis (BIA) by Farahbakhshian et al. evaluating velaglucerase alfa (VPRIVⁱ) and two other enzyme replacement therapies (ERTs), namely, imiglucerase (Cerezymeⁱⁱ) and taliglucerase alfa (Elelysoⁱⁱⁱ), for the treatment of patients with type 1 Gaucher disease (GD1) in a hypothetical 10-million-member United States (US) health plan¹. The results indicated that increased velaglucerase alfa uptake for GD1 treatment is cost-saving compared with the other two ERTs for the US health plan¹. However, we would like to highlight important limitations to be considered while interpreting this BIA.

In light of the considerable clinical burden associated with GD1, there are different treatment options available for its management. Of the three ERTs included in BIA by Farahbakhshian et al. imiglucerase was the first to be approved in 1994² and has been a standard of care for more than 20 years. It was followed by the approval of velaglucerase alfa in 2010³ and taliglucerase alfa in 2012⁴ for long-term treatment of patients with GD1. In addition, in 2014, eliglustat (Cerdelga^iv) a substrate reduction therapy (SRT) was approved in the US as the only oral first-line treatment for adults with GD1 who are CYP2D6 extensive, intermediate, or poor metabolizers, categories that encompass more than 90% of the general population^5,6. Its long-term efficacy and safety were shown in clinical trials^7–10 and real-world settings^11,12 for switched and treatment-naïve patients. Additionally, patients can benefit from the convenience of eliglustat, an orally administered drug taken at home with no-weight adjustment on the dose needed^9,10,13. Another SRT, miglustat (Zavesca^v), is indicated in mild-to-moderate adult patients with GD1 for whom one of the previously described ERTs is not a therapeutic option¹⁴.

We noted that Farahbakhshian et al. restricted their analysis of first-line therapies to only ERTs while excluding an oral first-line therapy, eliglustat, which can offer substantial cost savings over ERTs for eligible patients¹⁵. Eliglustat demonstrated safety and efficacy in naïve patients as well as comparable safety and efficacy to imiglucerase in switch patients^7–10. We would like to highlight the need for accurate prediction of BIA, which should account for eliglustat, already on the market at the time of this BIA publication. Therefore, we evaluated the inclusion of eliglustat in this published BIA to support informed decision-making in the management of GD1 from the US payer perspective.

Based on the labelled description^5,6, 90% of adult patients with GD1 are eligible for eliglustat treatment at the highest dose of two capsules (84 mg) per day. The wholesale acquisition cost (WAC) of $28,599.48 per pack of 56 eliglustat capsules¹⁶ was used to estimate the treatment cost to align with the 2021 ERT WACs used in Farahbakhshian et al¹. Average sales prices were not tested as they do not substantially change the results¹. The cost of an IV-administered drug accounts for a considerable amount of the total spent for payers and is reported to be $144,553 – $172,160 per patient per year in Farahbakhshian et al. Drugs administered orally at home incur no administration costs. Therefore, treating patients with oral eliglustat may present cost-saving for payers compared with ERT treatments.

First, we estimated the budget impact of eliglustat on the adult population from Farahbakhshian et al. compared with ERTs from the hypothetical 10-million US health plan WAC perspective over three years¹. If all eligible adult patients (102.6) were treated with eliglustat, it would translate to $49.7 million savings over three years, a substantial cost saving to payers (Table 1).

Table 1. Savings associated with eliglustat treatment in the adult population.

Approach	Farahbakhshian et al.^1 current scenario			Adjusted current scenario^a
	Velaglucerase alfa	Imiglucerase	Taliglucerase	Velaglucerase alfa	Imiglucerase	Taliglucerase	Eliglustat
Market shares each year	40.0%	53.0%	7.0%	4.0%	5.3%	0.7%	90.0%
Number of patients among the 114 adult patients^b	45.6	60.4	8.0	4.56	6.04	0.80	102.60
Yearly budget	$60,929,108^c			$44,369,893
Cost saving per year	-$16,559,215
Cost saving over 3 years	-$49.7 million

^aEliglustat shares are proportionally subtracted from all other treatment shares in Farahbakhshian et al. (e.g. 4% = 40.0% x [1–90%]). ^bPatients evaluated by Farahbakhshian et al¹. ^cRecalculated as a weighted average of annual acquisition costs and number of adult patients.

Second, we concede that not all GD patients eligible for eliglustat would switch to or initiate treatment with eliglustat. To study the extent of maintenance therapy in patients with ERT and switch to eliglustat, we conducted an adjusted analysis to estimate the budget impact with eliglustat being part of the market offer and the cost-saving option as presented above (Table 1). We used the eliglustat market share from Nalysnyk et al.¹⁵, to inform the distribution of the market shares in this adjusted ‘current scenario’ (Table 2). To have a similar analysis approach as the projected scenario by Farahbakhshian et al. we considered eliglustat taking 10% of the new market share each year instead of velaglucerase alfa. This resulted in $22.6 million savings over three years, highlighting that half of the savings i.e. $11 million, occurred due to a reduced administration and site-of-care-marked up cost. In addition to eliglustat oral treatment convenience, cost savings worth more than double the reported velaglucerase alfa savings of $8.67 million¹ is achievable by treating patients with eliglustat from the outset of treatment instead of ERTs.

Table 2. Comparison between Farahbakhshian et al.¹ velaglucerase alfa BIA and adjusted BIA with eliglustat on the market.

Approach	Farahbakhshian et al^1.			Adjusted scenario
	Original analysis			With eliglustat on the market^a
	Velaglucerase alfa	Imiglucerase	Taliglucerase	Velaglucerase alfa	Imiglucerase	Taliglucerase	Eliglustat
Current scenario	40.0%	53.0%	7.0%	35.2%	46.6%	6.2%	12.0%
Number of patients among the 114 adult patients^b	45.6	60.4	8.0	40.1	53.2	7.0	13.7
Projected scenario	+10% each year for velaglucerase alfa, proportionally subtracted across treatment shares			+10% each year for eliglustat, proportionally subtracted across treatment shares
Corresponding absolute change per year in market shares	+10%	−9%	−1%	−4%	−5%	−1%	+10%
Cost saving 1^st year	$1,448,595^c			-$3,769,992
Cost saving over 3 years	-$8.7 million^c			-$22.6 million

^aEliglustat shares are 12% from the published ‘current scenario’ of Nalysnyk et al. [15] and proportionally subtracted from all the other treatment shares in Farahbakhshian et al¹. (e.g. 35.2% = 40.0% x [1–12%]). ^bPatients evaluated by Farahbakhshian et al¹. ^cRecalculated from the difference between weighted averages of per patient annual costs (last row of Figure 3) and market shares in the current and projected scenarios (first column of Table 2) from Farahbakhshian et al¹.

The analyses presented above were developed for cost comparison only and do not take into consideration product safety, efficacy, or outcomes. The SRT for second-line treatment of GD1¹⁴ was also not included in the BIA, reducing the generalizability of the published results. In addition, Farahbakhshian et al. states that real-world use of ERT in GD1 may vary and the lack of sensitivity analysis using real-world data on doses of ERTs is a limitation within the reported BIA.

We would like to emphasize the important role of BIAs in assisting payers in making informed decisions for future spending. However, the BIA reported by Farahbakhshian et al. could potentially mislead the payers. This stems from the exclusion of eliglustat, a relevant oral treatment in the management of GD1^11,12,17 on the current market. In summary, this BIA analyses did not consider all the first-line therapies that can impact velaglucerase alfa reported cost-savings. The BIA by Farahbakhshian et al. is highly questionable and should not be used by the payers while making informed decisions in the management of GD1.

Transparency

Declaration of funding

No funding was received in connection with this Letter to the Editor.

Declaration of financial/other relationships

CR, MF, JH, GP, and RPJ are employees of Sanofi and may hold stock and/or stock options in the company.

Acknowledgements

Medical writing support was provided by Haimanti Mandal and Amit Kandhare (Sanofi, India).

Notes

i VPRIV is a registered trademark of Shire Human Genetic Therapies, Inc., Cambridge, MA, USA.

ii Cerezyme is a registered trademark of Genzyme Corporation, Cambridge, MA, USA.

iii Elelyso is a registered trademark of Pfizer Labs Division of Pfizer Inc., New York, NY, USA.

iv Cerdelga is a registered trademark of Genzyme Ireland, Ltd., Waterford, Ireland.

v Zavesca is a registered trademark of Actelion Pharmaceuticals US Inc., South San Francisco, CA, USA.