The landmark ODYSSEY Outcomes trial reported last March showed a hard clinical outcomes advantage and all-cause mortality reduction with alirocumab (Praluent). You can read 鶹ý's summary here. In this follow-up we examine how the trial has affected practice since then.
Many had hoped that positive findings from ODYSSEY Outcomes would build on the momentum from FOURIER the year before to bring down bureaucratic hurdles to reimbursement and boost use of PCSK9 inhibitors.
Although the relative 15% reduction in major adverse cardiovascular event risk associated with alirocumab (Praluent) wasn't the home run that might have propelled the drugs into their once-expected blockbuster status, the manufacturers went to work with what they had.
Right after the trial was presented in March, Sanofi and Regeneron announced their willingness to cut the price of alirocumab for any insurer that would ease access barriers.
Since then, "the majority of national pharmaceutical benefits managers and national insurers have joined with us to provide more straightforward access, which has reduced burdensome paperwork for HCPs and out-of-pocket costs for some patients," the companies said in a statement to 鶹ý.
In May, they struck just such a deal with the nation's largest pharmacy benefits manager, Express Scripts, making alirocumab the exclusive PCSK9 inhibitor for about 20 million commercially-insured people under the company's National Preferred Formulary.
In exchange for Express Scripts eliminating the burdensome requirements for laboratory results and detailed patient history (to be replaced by physician "attestation"), alirocumab would be discounted heavily to a net price of $4,500 to $8,000 per year beginning July 1.
Competitor Amgen took a different approach. Intent on fixing the high prescription abandonment rates for its PCSK9 inhibitor evolocumab (Repatha) among Medicare patients due to costly copays, the company announced in October it would slash the list price for evolocumab by 60% to $5,850 per year for everyone.
However, evolocumab's new national drug codes haven't yet been adopted into Medicare formularies and the changeover isn't expected to be finished until the end of 2020.
Prescriptions Rise, Differentially
Even so, evolocumab had a head start on alirocumab in prescriptions in 2018, according to public and private payor data from drug market research firm IQVIA (formerly IMS Health).
Both drugs started out fairly even in Q1 2017, before the results from the FOURIER trial with evolocumab had much chance to sink in.
But then evolocumab prescriptions started to climb faster, yielding an 85% increase year over year (from 66,168 in Q2 2017 to 122,670 in Q2 2018).
Alirocumab saw slower growth that added up to a 33% increase over the same period (49,611 to 70,164 prescriptions).
While IQVIA didn't yet have data on the third quarter of 2018 or beyond, a statement to 鶹ý from Sanofi and Regeneron noted that alirocumab growth has started to see the effects of payor deals.
"Based on net sales, our U.S. market share has grown significantly since the addition to the Express Scripts formulary: up to 40% in the third quarter, with the number of prescriptions continuing to increase steadily," the companies said, adding that the third quarter of 2018 saw a 62% year-over-year increase in global net sales.
An analyst who follows both companies had a different interpretation as to why evolocumab prescriptions so outpaced alirocumab's: intellectual property litigation. Prescribing patterns appeared to diverge after Amgen had won the case against Sanofi and Regeneron in 2017, sparking concern that alirocumab would be pulled from the market.
Amgen did not respond to requests for comment on this story.
Prescription Prognostics
The new pricing should help increase prescriptions of PCSK9 inhibitors through 2019, but the analyst predicted that payors will continue to restrict access this year.
"We understand more needs to be done to ease the burden still placed on patients and will continue to work actively with U.S. health plans to address these challenges," Sanofi and Regeneron said.
It remains to be seen how the national lipid guidelines released in November that boosted the profile of PCSK9 inhibitors in the treatment algorithm will impact prescribing and payor willingness to approve it.
An expanded indication for alirocumab awaits approval from U.S. and European regulatory agencies based on the ODYSSEY Outcomes trial results, with an expected response date of April 28 from the FDA.
Despite all the purported progress in widening access to PCSK9 inhibitors, the bureaucratic burden often remains daunting.
Roxana Mehran, MD, of Icahn School of Medicine at Mount Sinai in New York City, said she is still fighting for prescriptions when optimizing medical therapy upfront before coronary interventions. Recently, just one out of 15 of her patients was able to get a PCKS9 inhibitor, she told 鶹ý. As to the paperwork burden, "You need a full-time person just to be your scribe to do this work."