Luke Gormley, PharmD, BCPS, discusses how pharmacists are involved in the management of inclisiran.
In an interview with Pharmacy Times, Luke Gormley, PharmD, BCPS, a clinical pharmacy specialist at Allegheny General Hospital, discussed how pharmacists are involved in the management of inclisiran, a small interfering RNA treatment to manage low-density lipoprotein cholesterol (LDL-C). In addition to managing the treatment itself and educating patients, Gormley noted that pharmacists play a crucial role in implementing the treatment and establishing payment models.
Aislinn Antrim: Hi, I'm Aislinn Antrim with Pharmacy Times and I'm here with Luke Gormley, a clinical specialist for transitions of care at Allegheny Health Network with heart failure and acute myocardial infarction patients, to discuss inclisiran and what pharmacists really need to know. So, to start, what is inclisiran indicated for and how is it most commonly used?
Luke Gormley, PharmD, BCPS: Yeah, that's a good question. So, inclisiran is a small interfering RNA that is directed at PCSK9 mRNA. And why this is important is because PCSK9 typically tags LDL—or low-density lipoprotein—receptors for degradation. And so, this drug is able to stop the production of PCSK9 protein, which allows for more LDL receptors to actively clear that cholesterol out of the blood. In terms of its current approval or FDA indication, inclisiran is approved as an adjunct to diet and maximally tolerated statin therapy for adult patients specifically, and those patients usually have a history of either heterozygous familial hypercholesterolemia or clinical atherosclerotic disease, and who need additional lipid lowering medications.
So, what this boils down to is a patient population that typically meets usually 1 of 2 criteria: Those with a history of intolerance to other lipid lowering medications, including a statin, usually plus a documented intolerance or allergy to other PCSK9 inhibitor medications that are already on the market, or to patients who have not reached their LDL goal on a regimen that includes a high intensity statin and usually a PCSK9 inhibitor that's already on the market. This second group of patients is usually identified by clinicians after other FDA-approved medications have been exhausted, and usually involves a risk versus benefit discussion, given the fact that we're currently lacking secondary prevention cardiovascular outcomes data with inclisiran and just based on the fact that the medication was newly approved. And those clinical trials are currently ongoing.
Aislinn Antrim: Perfect. Can you review some of the data behind its use?
Luke Gormley, PharmD, BCPS: Yes, so inclisiran has a myriad of clinical trials that have been published and that are ongoing. It all starts with ORION-1, which was simply a trial that looked at, over a period of time, could inclisiran sustain LDL reductions and what was that period of time? So, in that clinical trial, ORION-1 patients received either 1 or 2 doses of inclisiran and the study investigators studied how long it took for patients to get back to their baseline LDL. And what they found was that patients who receive 2 doses of inclisiran and were studied over a period of about a year responded better. And there was a statistically significant reduction and sustained reduction in LDL-C in those patients that did receive inclisiran in 2 doses.
From a maybe a bit more LDL-lowering perspective from clinical trials, there are several of them that have been published. So, ORION-9 specifically looked at patients with a history of heterozygous familial hypercholesterolemia, and ORION-10 and 11 looked at patients with a history of ASCVD or an equivalent and looked at sustained LDL reductions over a period of time up to almost 2 years. So, if you look at the findings from those 3 clinical trials, ORION-9, 10, and 11, with a kind of a different patient population, their LDL was reduced on average by 40% to 50% in those patient populations. Now, where we're really looking forward to with inclisiran in the future is with a clinical trial called ORION-4 and VICTORION-2P. And those clinical trials are going to be looking at more secondary prevention of cardiovascular events, specifically those that are called major adverse cardiac cardiovascular events, also known as MACE. And those findings are expected to be published somewhere between the summer of 2026 and the fall of 2027.
Aislinn Antrim: Wonderful, very interesting. You've been point person for the implementation of inclisiran at the Allegheny Health Network. What has this process looked like and what considerations have really come up?
Luke Gormley, PharmD, BCPS: Yeah, I think inclisiran somewhat surprised us all in terms of maybe the need for a lot of pharmacist involvement, simply from the fact that it's a subcutaneous medication. Like the other PSCK9 medications that are on the market, it's given less frequently. So, it's given initially at month 3, and then every 6 months thereafter. And because of that longer duration between injections, it's really been decided amongst the manufacturers and, you know, clinicians at this point for the need for those patients to be seen by health care providers or for the medication to be administered in a health care setting, simply because that's a long duration. And it [would be] really hard to ensure that patients would remain on schedule if we were unable to administer the medication to them. So here across Allegheny Health Network, we felt like it was appropriate for our pharmacists to begin to help our clinicians identify candidates, help the teams figure out how to submit for medication approvals and procure the medication, and bill for those medication administrations, because in a health care administered setting, from a medication standpoint, that usually generally flips where the medication is billed to the medical benefit versus the pharmacy benefit. And from a cardiovascular medicine management perspective, this is the first medication that really has made its way into the medical benefit in terms of procurement and billing for patients in this world. So that's a really large shift for our clinicians, nurses, and pharmacists to be making their way to. And so, because of that, we felt that pharmacists would be greatly positioned to help clinicians figure out that process.
Aislinn Antrim: Absolutely. Well, speaking of that, how are pharmacists involved and why is that involvement so crucial?
Luke Gormley, PharmD, BCPS: Yeah, so as I was talking about a little bit before, we felt that a guideline to help clinicians begin to figure out where inclisiran may fit into practice for their patients and figure out those foundational principles about the drug safety profile would be super important for our clinicians, since we've never done this for medication in the cardiovascular space. So, a large focus of our education and rollout was focused on prior authorization, approval, and process for procurement of the medication.
So, at AHN, or Allegheny Health Network, we currently request that our clinicians send an initial prescription to our specialty pharmacy mostly to figure out if the medication could be filled or billed under the traditional pharmacy benefit, because that tends to be the path of least resistance or a little bit easier and more familiar for our clinicians. And it allows for someone like myself to be included in the discussion about appropriate patient candidates for a medication that has a complex administration procurement and billing process. And sometimes we're able to decide or figure out if a different medication may be more clinically appropriate. But why this process also is helpful is at that point, if the medication can't be billed under the pharmacy benefit, we've also developed a process internally and in collaboration with the manufacturer to figure out if the medication would be covered under the patient's medical benefits, and if so what the cost implications of that would be. And I think that's a really important piece, because when we're adjusting where this medication is being billed, there's an opportunity for the patient to receive a bill that they're not sure of or they're not anticipating getting because it's in the medical benefits, where we're not really used to seeing co-pays outside of maybe doctor's visits or for routine bloodwork. And it also ensures that our clinics are getting reimbursed for the medications that they're administering because they're essentially buying those medications and then billing the patient and their insurance for it after the fact.
In terms of quality improvement or following up with our current guideline implementation, during the last 10 months, we've attempted to adjust our guidance regarding inclisiran based in providing nurses and other physicians with tips about documentation and billing. And we've also adjusted J-codes and CPT billing codes as they become permanent for inclisiran in the last couple of months. Currently, our goal is to review data from each clinic to ensure that our guideline is working as intended. And we also plan to audit the billing practices to ensure that our clinics are getting reimbursed and that patients aren't receiving erroneous bills, as well.
Things to note, since we are collaborating very closely with other nurses and physicians from a pharmacist perspective, we have been getting feedback from our nursing staff. And they've requested that we focus on creating a more streamlined process for submitting requests for initial benefits, inquiries. And so, we take that very seriously and our goal is to change our process with a few minor billing updates to be fully built into our electronic medical record. Therefore, we can minimize manual typing and inputs by our staff at various clinical sites and we hope that this will allow for other clinicians as they begin to use inclisiran or inquire about using it, that they'll be able to follow this guidance seamlessly, and train and introduce it to others when they need to.
We also plan on getting feedback from our staff regarding their current practices for tracking and storing inclisiran, since it does get bought by our clinics and then it gets shipped to them or delivered to those clinics. And we also want to know how clinics have been able to follow up with patients in terms of scheduling their injections or keeping track of prior authorizations that are going to expire. We are hopeful that, again, some of these clinics may have thought of how they want to track their patients, but we also think it's an opportunity for us to be able to help our clinics figure out the right process for tracking the medication and also keeping track of their patients and their prior authorizations. Because, at the end of the day, this is different from a management perspective or medication management perspective. And we want to make this as easy as possible for our clinicians who may be thinking about using this medication in the near future.
Aislinn Antrim: Wonderful. Are there any adverse effects or treatment considerations that pharmacists should be aware of and involved in?
Luke Gormley, PharmD, BCPS: So, inclisiran in general is relatively well tolerated. The most commonly reported side effects in clinical trials were injection site reactions and this was also the most common reason for patients to discontinue therapy in the inclisiran arm of the ORION-9, 10, and 11 clinical trials. From a warnings, precautions, and contraindications perspective, there's none listed in the package inserts. Any currently published safety data including patients who are of an advanced age or have hepatic or renal impairment, but not including end stage liver or renal disease—those patients do not appear to have any different effects of inclisiran during clinical trials as well. The other thing that's really important is that because of how the medication works and is metabolized, there are no expected drug-drug interactions, or even drug supplement interactions. As we know, it's becoming increasingly common for patients to be using natural supplements as well, in addition to their prescription medications.
Aislinn Antrim: Very interesting. Is there anything you want to add or anything that I didn't think to ask about?
Luke Gormley, PharmD, BCPS: Yeah, one thing I forgot to mention earlier about pharmacists being involved in treatment considerations is the piece about counseling patients if they are pregnant or becoming pregnant. This falls into the same category as any cholesterol-lowering medication that can influence cholesterol synthesis, and so patients just need to have a risk-versus-benefit discussion with their physician if they need to or if they want to continue therapy, just given that there could be potential risks to a fetus.
In terms of how inclisiran arrives to the clinic, it comes in a prepackaged, prefilled syringe, and it's intended to be stored at room temperature. It requires no manipulation at all prior to patient administration, and it is administered subcutaneously. The other thing to keep in mind is that both the needle and the needle cap are latex free. In terms of kind of taking it full circle in terms of clinical practice, I would anticipate that some of the other medications that are currently on the market, the other PCSK9 inhibitors, may find their place before inclisiran right now, specifically from the fact that we're currently missing secondary prevention outcomes data from our cardiovascular outcomes perspective. As I've shared previously, those data are going to be published, but not for a bit of time. And from the perspective of that, the other medications are billed for and administered under the pharmacy benefit, which is the more traditional and potentially easier to access benefit that we’re most used to from a cost perspective. The other PCSK9 inhibitors and inclisiran are relatively the same price, but from an authorization perspective, and from generally what we've been seeing, at least from my perspective from an insurance piece, most insurers are requesting that a patient be on a maximally tolerated statin and have tried and failed a PCSK9 inhibitor. And again, I anticipate that simply because of limited evidence in some patient populations, not necessarily because it's not good at lowering LDL, because of those other pieces.
Aislinn Antrim: Absolutely. Thank you so much; this has been such a great overview. Thank you for talking with me about it.