Memorandum

ADA updates 2019 Standards of Care to include DECLARE (AZ’s Farxiga) and REDUCE-IT (Amarin’s Vascepa) data – March 28, 2019

Farxiga recognized for benefit on heart failure hospitalizations and CKD progression, safety in moderate renal impairment; Novel recommendation of Vascepa for triglyceride lowering in diabetes with ASCVD/high CV risk

ADA just updated its 2019 Standards of Care to incorporate data from the DECLARE CVOT for AZ’s Farxiga and the REDUCE-IT CVOT for Amarin’s Vascepa, as well as Farxiga’s label update approving use in moderate renal impairment.

As a reminder, ADA published its 2019 Standards of Care in December 2018, and these are the first updates since its initial publication. In light of the ever-growing intersection between diabetes, CVD, and CKD, the ADA deemed it an “urgent need to update the Standards of Care to ensure optimal treatment recommendations.”

The Standards became a living document starting with the 2018 Standards of Care – see all updates since then here. We salute the ADA’s commitment to creating a true Living Standards of Care that integrates recent research in the constantly evolving diabetes ecosystem.

  • Data from the DECLARE CVOT is now included in Sections 9, 10, and 11, highlighting Farxiga’s benefit on hospitalization for heart failure (27% relative risk reduction) and CKD progression (47% RRR on composite of 40% decrease in eGFR to <60 ml/min/m2, ESRD, and renal death). Notably, in ADA’s treatment algorithm, dapagliflozin is now recommended (along with empagliflozin and canagliflozin) as an SGLT-2 inhibitor with evidence of reducing HF and CKD progression in large CVOTs. We hope that this class-wide recognition will help improve both access to SGLT-2s and utilization of the class for reducing CV and renal risk. Elsewhere, Section 11 of the Standards was also updated to reflect FDA’s recent approval of Farxiga in moderate renal impairment, bringing AZ’s SGLT-2 in line with Lilly/BI’s Jardiance and J&J’s Invokana (100 mg dose only).

  • In a groundbreaking recommendation the Standards now reflect data from the REDUCE-IT CVOT for Amarin’s Vascepa (icosapent ethyl) and give a Level A recommendation that icosapent ethyl be considered for patients with diabetes and ASCVD or other CV risk factors (i.e., primary or secondary prevention), who are on a statin but have high triglycerides (125-499 mg/dl). The REDUCE-IT trial demonstrated a highly significant 25% RRR on a four-point MACE of CV death, MI, coronary revascularization, and unstable angina, and 59% of participants had type 2 diabetes (including the entire primary prevention cohort). Data just presented at ACC 2019 show a similarly positive 30% RRR on total CV events.

    • This is a huge win for Amarin as it strives to expand Vascepa’s reach and should go a long way in familiarizing HCPs with the unique triglyceride-lowering therapy – the company put out a press release on the update. Encouragingly, Amarin management has remained committed to offering Vascepa at a low cost ($3/month on average with a co-pay card) to ensure broad access and affordability, even in light of investor pressure to increase prices following REDUCE-IT’s readout.

    • Of note, this recommendation precedes even FDA’s approval of a CV indication for Vascepa, for which the company is in the process of submitting an sNDA. Vascepa is currently FDA-indicated for treatment of very high triglycerides (≥500 mg/dl), but Amarin recently submitted a supplemental new drug application (sNDA) to the FDA seeking an expanded indication for reducing the risk of MACE.

 

--by Martin Kurian, Ann Carracher, and Kelly Close