Specialty pharmacists are well positioned to include pharmacogenomics (PGx) in clinical workflow and improve patient outcomes, safety and cost efficiency. But in health system-based specialty pharmacy and other sites of care, considerable implementation barriers remain, presenters noted at the 2024 NASP Annual Meeting & Expo, in Nashville, Tenn.
In this final installment of a seven-part series, PGx experts make the case for why overcoming these barriers is critical. The key driver? “Greater than 99% of people have at least one [genetic] variation that impacts, on average, over 10 commonly prescribed medications that a patient will take,” said Kristine Ashcraft, the president and CEO of YouScript, a precision software system that integrates PGx testing into prescribing practices (Genet Med 2019;21[6]:1345-1354). “This really drives home the importance of committing to integrating pharmacogenomics in practice,” she stressed.
“We have the standards, we have the technology,” Ms. Ashcraft added. “We just need to push it through the system and make it a priority.”
PGx is relevant to a wide array of specialties, including cardiology, oncology, psychiatry and pain management (see box). “One in 5 prescriptions are currently impacted by pharmacogenomics,” said Ms. Ashcraft, citing a U.K. study that included almost half a million patients (Br J Clin Pharmacol 2021;87[7]:2907-2925). Furthermore, an actionable drug–gene interaction was present for roughly 1 in 11 of all new prescriptions for 56 drugs the researchers analyzed.
The FDA has also stated in drug development guidance that drug–gene interactions are similar in scope to drug–drug interactions and should receive similar attention (bit.ly/4hQWeVG). And, like drug–drug interactions, drug–gene interactions can be potentially fatal. For example, pathogenic variants of the DPYD gene dramatically increase the risk for treatment-related death for patients taking standard-dose fluoropyrimidine chemotherapy (Oncologist 2021;26[12]:1008-1016).
Emerging Standards
To ensure consistent industry standards for PGx labs, the Standardizing Laboratory Practices in Pharmacogenomics (STRIPE) Collaborative Community, an initiative of the American Society of Pharmacovigilance, held its inaugural annual meeting in Washington, D.C., in October. “The goal is to align consensus around key areas such as what it means to be a good pharmacogenomics lab, and what it means to appropriately share the results, so pharmacogenomic information can follow you wherever you receive care and continue to improve that care,” Ms. Ashcraft said.
The reason for that? In the early days of PGx testing, some shady practices led to limitations on insurance coverage for these tests. “Unfortunately, there were some bad players early on, and local coverage determinations were issued that stopped coverage,” Ms. Ashcraft said. (Several PGx labs had Medicare payments suspended after evidence came to light that suggested they were using improper tactics to pressure doctors to order tests, as well as other allegations of fraud [bit.ly/3UZc7zD].)
“Fortunately, that has changed, and a Medicare local coverage determination has been in place since 2020,” Ms. Ashcraft said. “Biomarker testing legislation at the state level, led by the American Cancer Society [Cancer] Action Network, mandates that Medicaid and commercial coverage follow suit.” At press time, at least 15 states required biomarker testing coverage for all state-regulated plans; five more required it for at least some plans; and legislation had been introduced in at least nine other states.
Specialty Drugs For Alzheimer’s, MS and Other Conditions Affected
Hundreds of medications have been approved with PGx biomarker information listed in the product labeling (bit.ly/3UAzIHi). Many of these are specialty drugs, such as the multiple sclerosis (MS) disease-modifying therapy siponimod (Mayzent, Novartis); lecanemab-irmb (Leqembi, Eisai and Biogen), an amyloid beta-directed antibody indicated for the treatment of Alzheimer’s disease; and oncologic agents such as osimertinib (Tagrisso, AstraZeneca) and pembrolizumab (Keytruda, Merck). The labeling for some, but not all, of the products includes specific actions to be taken based on the biomarker information, and some drugs are now being approved with companion PGx testing required.
For example, the FDA-approved drug labeling for siponimod, the first oral treatment for secondary progressive MS, requires testing to determine the cytochrome P450 2C9 (CYP2C9) genotype. The specialty drug is contraindicated in patients carrying a CYP2C9×3/×3 genotype, and a daily maintenance dose of 1 mg is required in patients with CYP2C9×1/×3 and ×2/×3 genotypes (Biomed Pharmacother 2022;153:113536). Another example is lecanemab-irmb. This specialty pharmacy medication, like others in its class, requires testing for the APoE gene variant because people who are homozygous for APoE4 are at significantly increased risk for amyloid-related imaging abnormalities, which may signal the presence of microhemorrhages and other cerebral complications (Alzheimers Dement 2011;7[4]:367-385).
Most of the cancer drugs with PGx tests (including osimertinib and pembrolizumab) are for efficacy/targeting, the speakers noted.
Casting a Wide PGx Testing Net
Rather than testing for single-gene variants, comprehensive PGx panels are preferred, said Ms. Ashcraft, noting that single-gene testing may overlook significant interactions and variations that could affect a patient’s overall medication regimen, potentially resulting in adverse drug reactions. “In an analysis I co-authored, we reviewed data on about 30,000 patients who had a pharmacogenomic panel, and we found that almost 60% of them had a clinical drug–gene interaction in more than one area—a mental health medication, a cardiology medication, a specialty medication and a pain medication,” she said. “This is incredibly common, and that’s just what was found at one point in time” (J Pers Med 2022;12[12]:1972).
The STRIPE meeting in October recommended that all PGx lab results be incorporated into the patient’s electronic health record (EHR) as discrete results, defined as health data stored at the lowest level of granularity, using common standards such as those from Health Level Seven International. Usually taking the form of genotypes and phenotypes, these discrete PGx test results allow data to be measurable and reportable within the EHR system, and therefore used for clinical decision support and medication management.
“People move from plan to plan a lot, especially on commercial insurance, so a payor ought not to have to reimburse for a panel again if the last payor covered it,” Ms. Ashcraft said. “That information needs to be kept alive consistently across the industry, leveraging these standards we already have.”
Accelerator Gives PGx Implementation a Boost
To advance the use of pharmacogenomics (PGx) in hospitals and health systems, ASHP and the University of Minnesota College of Pharmacy partnered to offer the Pharmacogenomics Accelerator (bit.ly/3Z1MaRs). The 12-month program, which has trained two cohorts, helps pharmacists develop PGx services at their institutions and build PGx clinical skills. The training includes virtual meetings, webinars and sessions with coaches assigned to participating sites.
The 2023-2024 cohort included Cambridge Health Alliance, in Massachusetts, which launched PGx testing this summer. “We wanted to be prepared as this becomes more popular in terms of patients asking for pharmacogenomic testing or coming to us with results,” Lauren Sullivan, PharmD, a clinical pharmacist at the health system, said in a profile from ASHP (bit.ly/4fub6YH).
Another member of the cohort is Henry Ford Health System, in Michigan. Long To, PharmD, BCPS, a PGx specialist leading development of the health system’s PGx program, commented in another ASHP profile that program-building guidance and networking opportunities were valuable aspects of the Accelerator. “I can tap into relationships I’ve developed with these experts who I would likely see at future conferences or be able to contact for advice,” he said (bit.ly/4fSovtd).
Suzanne Stevens, PharmD, BCOP, an oncology pharmacy manager at Wentworth-Douglass Hospital, in Dover, N.H., shared insights from participating in the program’s first cohort during the ASHP 2023 Midyear Clinical Meeting & Exhibition, in Anaheim, Calif. “Pharmacogenomics allows us to maximize therapeutic effects, improve outcomes and minimize toxicity,” she noted. To achieve these benefits, the hospital initially targeted oncology and surgical patients for PGx testing who were taking more than five medications or experiencing significant medication side effects. Of more than 100 patients tested, 10% received dose adjustments for the chemotherapy drugs 5-fluorouracil and/or irinotecan, and three complex patients referred from surgical services also received changes in medication management. The hospital plans to expand its PGx offerings to introduce features such as referrals to pharmacists for PGx testing and point-of-care testing. “This is very much a very pharmacist-driven service line at our hospital,” Dr. Stevens said.
One advantage of participating in the Accelerator was learning from other institutions in the cohort. “You get to see what their struggles are, but you also get to see what their triumphs are,” Dr. Stevens said. “And it’s a great little network to lean on so that you can ask more questions.”
Her advice? “Don’t let great get in the way of good. Sometimes you just need to get started.”
The Pharmacogenomics Accelerator program is on hiatus, according to an ASHP spokesperson.
Pharmacists as ‘Quarterbacks’
Pharmacists should be the “quarterbacks” in directing the use of PGx data in medication management, said Kelee Petzelt, the director of business development at the health technology company Invaryant. “They’re the ones with the expertise on the medication, and they’re the ones that have the best access to the patient,” Ms. Petzelt said. “The physician that has seven minutes to talk to me is never going to get through my pharmacogenomics test, even if it’s just one issue we’re talking about. So why should we put all of that effort there when the pharmacist is the expert on medication, they have a little more time, and they definitely are more accessible to people who work and can’t get doctors’ appointments?”
Ideally, pharmacists should be reimbursed for this function, the experts said. “Pharmacists today do medication reviews based on what they have currently in the system, and they are paid for that. And if you add the pharmacogenomics review, that will lead to better outcomes, lowered hospitalization rates and so on,” Ms. Petzelt said. “So, they should be reimbursed more for that more thorough review.”
In a randomized trial at a hospital-based home health agency, using PGx panel testing and YouScript’s PGx decision support tool in polypharmacy patients ages 50 years and older, rehospitalizations and emergency department (ED) visits at 60 days were both significantly reduced (P=0.007 and P=0.045, respectively) (PLoS One 2017;12[2]:e0170905).
“We also found a $4,832 savings per patient over the 60-day period, driven primarily by those reduced ED visits and hospitalizations,” Ms. Ashcraft said. “As we move into value-based care, ideally, pharmacists will get paid to change the drugs or dosages when appropriate based on pharmacogenomic panel results. It’s a medication intervention that matters a lot, and we want to incentivize those things that we know improve care, and pay the people with the highest amount of training to incorporate that information.”
Drug manufacturers will also be increasingly focused on targeting the right patients with PGx biomarker–based testing, said Wilson Tam, PharmD, the director of sales engineering at Inovalon. “It’s in their best interests to ensure that the right patient gets the right medication. So, a manufacturer will want to point their patients toward networks of pharmacies that are comprehensively incorporating pharmacogenomics within their workflow.”
The NASP panel urged pharmacists to support the bipartisan Right Drug Dose Now Act, introduced in Congress in March by Reps. Eric Swalwell (D-Calif.), the co-chair of the Personalized Medicine Caucus, and Dan Crenshaw (R-Texas). The legislation aims to update the National Action Plan for Adverse Drug Event Prevention by integrating advancements in PGx research and testing. It would also:
- create a healthcare provider educational campaign focused on preventing adverse drug events, in part by using evidence-based PGx information;
- incentivize updates to EHR systems to ensure that healthcare providers are alerted to interactions between medications and genes when making prescribing decisions; and
- enhance reporting systems that would assist with the reporting of PGx-associated adverse drug events.
A second associated bill would authorize sustained funding for PGx implementation research and guideline development. “If we can flag for drug–drug interactions in the EHR, we can certainly flag for drug–gene interactions and appropriate testing as well,” Ms. Ashcraft said.
The sources reported no relevant financial disclosures.
More PGx Coverage
Don’t miss the previous installments in our 2024 series on pharmacogenomics:
This article is from the December 2024 print issue.