The ‘buy-and-bill’ coverage model
This difference in drug administration between inclisiran and the antibody-based PCSK9 inhibitors set up Novartis to promote insurance reimbursement for inclisiran using a “buy-and-bill” paradigm that was first developed for oncology drugs and which may provide a loophole around the prior-authorization roadblocks that hindered early uptake of the antibody-based PCSK9 inhibitors.
It’s also an approach that has made U.S. clinicians unsure how it will play out in practice. Infrequent inclisiran dosing may also boost patient compliance.
“Adherence is the greatest challenge in preventive cardiology, and thus inclisiran has the potential to be a game changer,” commented Christie M. Ballantyne, MD, professor and chief of cardiology at Baylor College of Medicine, Houston.
“Will it be easier for physicians to write a prescription and for patients to get the medication without a demanding and frustrating prior-authorization process?” he wondered during an interview. “I’m waiting to see how this unfolds, especially in systems where pharmacy is not fully integrated with the outpatient setting. In some ways, this is as big of an experiment as was development of the drug,” Dr. Ballantyne said.
Although the prior-authorization hoops for evolocumab and alirocumab have become easier to jump through, “most physicians don’t have the resources to handle it and don’t bother,” noted Dr. Davidson, and he’s concerned that infrastructure challenges will also hamper the buy-and-bill strategy for inclisiran.
He also expressed skepticism that the prior-authorization barrier will disappear. “Payers don’t want to open a large population to a very expensive drug without some gatekeeping,” he said, while acknowledging that in late January 2022 he did not yet have personal experience administering inclisiran or navigating its insurance reimbursement.
Boosting patient compliance
Dr. Davidson agreed that the prospect for enhanced patient compliance with inclisiran was intriguing and had already drawn the interest of some of his patients.
“There is a lot of appeal” to a treatment that’s only given once every 6 months, he said. “Compliance is a major issue, and this is less work for patients.”
“The biggest possible attraction of inclisiran is that it is given twice a year, but whether this plays out as anticipated in the real world need to be seen,” cautioned Vijay Nambi, MD, a cardiologist at the Michael E. DeBakey VA Hospital, Houston, and at Baylor College of Medicine who has written about inclisiran. He noted that while two doses a year is “on paper very attractive,” this scheme opens the door to missed or delayed appointments because of vacations, other patient travel, or events like a pandemic.
“The biggest pro for inclisiran is the dosing schedule,” said Chandni Bardolia, PharmD, a drug information specialist at Tabula Rasa Healthcare, Moorestown, N.J., who has analyzed and written about inclisiran and other lipid-lowering medications. “Twice yearly dosing following initiation will be a huge benefit to improve adherence and reduce the number of injections.”
However, inclisiran’s attractive dosing schedule as well as its safety and potent efficacy do not tell the whole story, she highlighted in an interview.
Inclisiran’s clinical evidence still cooking
“I see inclisiran as a last-line drug, mainly because the current alternatives have more safety and efficacy data,” Dr. Bardolia said.
Inclisiran’s “cost and the fact that there are other agents with clinical outcome data already available [alirocumab and evolocumab] means inclisiran is not a first-line agent after statins,” agreed Dr. Nambi.
The FDA based its inclisiran approval entirely on the drug’s demonstrated safety and LDL-lowering efficacy. The cardiovascular outcomes trial for inclisiran, ORION-4, with about 15,000 enrolled patients, started in 2018 and remains in progress with full results expected in 2026.
The lack of clinical outcomes data for inclisiran is a major limitation, said Neil J. Stone, MD, a cardiologist and professor at Northwestern University, Chicago, and vice chair of the panel that wrote the most recent cholesterol guideline for the American College of Cardiology and American Heart Association.
“My greatest concern is the lack of outcome trial data. That’s very important,” Dr. Stone said in an interview.
But others minimize this limitation given the overwhelming evidence that links lower levels of LDL-cholesterol to reduced clinical events.
Most clinicians “support lower LDL as a surrogate” for reduced clinical events, “just like blood pressure and hemoglobin A1c,” noted Dr. Davidson, although he conceded that a “substantial minority wants to wait to see inclisiran’s outcome benefits.”
It’s all about price
While opinions are mixed on the need for clinical outcomes data, experts are more uniform in seeing drug prices that run to several thousands per year as the main uptake issue.
“We need to look at the cost-efficacy with inclisiran, and we need benefit data to determine this,” said Dr. Stone.
“Outcomes data are central to characterizing value. I imagine that costs will impact adoption and dissemination” of inclisiran, commented Paul L. Hess, MD, a cardiologist at the Rocky Mountain Regional VA Medical Center, Denver.
Patient interest in less frequent dosing will be important for driving use, but “ultimately cost will be the most important driving factor,” for inclisiran uptake, commented Robert H. Eckel, MD, an endocrinologist affiliated with the University of Colorado School of Medicine, Aurora.
Dr. Davidson has ties to New Amsterdam Pharma and Amgen, which markets evolocumab (Repatha). Dr. Ballantyne is a consultant to numerous companies, including Amgen and Regeneron, which market alirocumab (Praluent). Dr. Nambi has been a site investigator for studies sponsored by Amgen, and by Merck, which markets the LDL-cholesterol drug ezetimibe (Zetia) and is developing an oral PCSK9 inhibitor (he said that the views he expressed are his own and don’t represent that of the department of Veterans Affairs or Baylor.) Dr. Bardolia had no disclosures beyond her employment at Tabula Rasa Healthcare. Dr. Stone, Dr. Hess, and Dr. Eckel had no relevant disclosures.