Subcutaneous Versions of IV Oncology Drugs Can Offer Various Benefits

Reprinted with AIS Health permission from the May 2025 issue of Radar on Specialty Pharmacy

Multiple oncology drugs that first launched as intravenous (IV) infusions are now available as subcutaneous (SC) injections. The new formulations can provide advantages such as shorter infusion times, which can benefit both patients and crowded infusion suites. But an array of considerations should be taken into account, and not every patient may be a suitable candidate for the therapies.

Among the agents are Roche Group member Genentech USA, Inc.’s Herceptin Hylecta (trastuzumab and hyaluronidase-oysk) and Tecentriq Hybreza (atezolizumab and hyaluronidase-tqjs), Johnson & Johnson Innovative Medicine’s Darzalex Faspro (daratumumab and hyaluronidase-fihj) and Bristol Myers Squibb’s Opdivo Qvantig (nivolumab and hyaluronidase-nvhy). Merck & Co., Inc.’s SC Keytruda (pembrolizumab) is awaiting an FDA decision on its approval, which is expected by Sept. 23.

In certain cases, such as when someone is on multiple IV agents, the person likely will remain on the IV formulation, explains Tara Higgins, Pharm.D., senior clinical consultant at Pharmaceutical Strategies Group (PSG), an EPIC company. “The use of a SC formulation is an attractive option when it is used as monotherapy versus part of a chemotherapy regimen that includes other IV therapies,” she says. “Individuals on oral cancer therapies combined with a targeted therapy could be an additional patient population that may opt for the SC formulation in place of the IV.”

Other reasons for preferring the IV formulation would be avoiding “multiple patient sticks, not only for the drug administration but also for associated laboratory and monitoring tests,” states Andy Szczotka, Pharm.D., chief pharmacy officer at AscellaHealth. “The post-monitoring period is also a consideration,” as are the drugs’ safety profiles. While they “generally have the same safety concerns, the SC formulations may tend to have higher local site reactions, which could limit this route of administration for patients. Also, higher rates of local immunogenicity and antibodies may be a factor for the SC route.”

In addition, he tells AIS Health, some people simply prefer the IV route of administration because it allows for “more interaction with their health care providers and their patient support network.” Still, the new formulations have benefits. They offer much shorter administration time: about five to seven minutes vs. 30 minutes to a few hours, which is especially helpful if the drug is being given as a monotherapy.

In addition to the shorter administration time, the SC drugs take less time to prepare, points out Szczotka. That, in turn, also will help free up capacity in infusion centers. In addition, “SC administration may reduce ancillary health system expenses such as IV kits, administration sets, drug preparation times, and nursing administration and monitoring times.”

He notes that studies have found that most patients prefer SC administration over IV for a variety of reasons, including shorter visits, “administration comfort, reduced emotional distress related to the treatments and greater satisfaction with their overall cancer therapy.”

Most Are Similar in Efficacy

According to Szczotka, “some studies have reported that the SC route of administration may potentially show improved patient response through longer duration of response, better progression-free survival and improved overall survival. Most studies of the SC formulations tend to show that the SC and IV formulations are similar in efficacy and patient outcomes.”

But that’s not the case for all of them.

The issue was highlighted earlier this year, after Blue Cross Blue Shield of Michigan issued a provider alert on Feb. 6 explaining that as of May 1, it would require people in its Medicare Plus Blue and BCN Advantage plans to try and fail on Darzalex before they could use Darzalex Faspro.

In a LinkedIn post pushing back against the decision, Ming-Hei Tai, Pharm.D., an oncology pharmacist at Karmanos Cancer Institute, pointed out that when the drug was available only as an infusion, “about half of patients would have an infusion-related reaction, most often during the first dose, and patients had to receive 8-hour infusions due to this risk,” with some people receiving their initial dose in the hospital. In comparison, he wrote, less than 10% of people on the SC formulation have a reaction to it, “and most reactions occur in the first 3 hours of the first dose.”

He maintained that the Blues plan’s move was because the IV cost about $600 more per infusion and noted that some other IV/SC products had equivalent pricing. But Darzalex Faspro, he said, “is genuinely a better product, which is why it is priced higher.”

“Blue Cross isn’t the one who has to find 8 hours of chair time for patients,” he wrote. “They’re not the ones who need to find a nurse to titrate up the infusion rate and monitor the patient. They’re not the ones who have to gather around a patient and give rescue medications, which essentially puts all the other infusions that day on hold.”

On Feb. 19, the plan issued a new provider alert stating that it would not require step therapy for Darzalex Faspro. When Formulary Watch asked why it decided to not implement the change, the Blues plan wouldn’t comment “on what happened or why.”

Both formulations require pre-infusion medications to lessen the chance of a reaction, points out Higgins, who agrees that “Darzalex Faspro has shown lower systemic administration-related reactions (ARR) in comparison to Darzalex. Tecentriq is another targeted therapy where the SC version has lower ARR than the IV administration. Opdivo SC has a similar reaction profile to the IV administration. In general, the targeted therapies like Darzalex, Opdivo, Tecentriq and Keytruda are better tolerated than chemotherapy regimens.”

However, that’s not always the situation, says Szczotka, who points to trastuzumab. Its SC formulation “was similar in the incidence of adverse effects to the IV formulation, [but] more patients had adverse reactions that were classified as serious due partly to infections and infestations. However, over a six-year period, the overall incidence of adverse events between the two groups was similar.” Additional trials found that patients had more adverse reactions and twice as many antidrug antibodies after switching from IV to SC administration.

Ultimately, he says, “the systemic side effect profile may be greater with the IV administration of products compared to the SC administration, as well as a higher incidence of infusion-related reactions, whereas the local site effects may be greater with the SC route.”

Approach to Pricing Varies

While a difference exists in pricing for the Darzalex agents, others, such as Tecentriq and Opdivo, are priced the same for both formulations, says Higgins. But there are factors beyond different wholesale acquisition cost (WAC) to consider, says Szczotka. While the SC formulations have less labor costs, they may require higher dosages to attain a similar therapeutic response. For instance, he says, “for a typical 70 kg patient, Darzalex Faspro drug cost is approximately 23% higher than the comparable dosed IV formulation.”

Another cost consideration for payers is that the new formulations allow drugmakers to extend a product’s line when it is approaching the end of its patent, allowing the SC formulations to avoid biosimilar and generic competitors, Szczotka points out. “Generics and biosimilars have the opportunity to provide significant drug-related cost-saving opportunities, which could overshadow other health system savings.”

As of now, health care professionals must administer the SC versions, allowing them to be given in not only an infusion suite but also a provider’s office or even the home setting by an infusion nurse following initial administration in a health care setting. But the agents may require pre-medication and a monitoring period, so a provider office may have issues with administration. For example, Szczotka explains that trastuzumab requires post-infusion observation for six hours after the first administration and two hours for subsequent dosing.

“An IV infusion center may be able to treat and monitor multiple patients simultaneously,” he states. “While SC products are typically administered over a shorter time interval than their IV formulation, monitoring recommendations may be similar between the different formulations and may be a hurdle for in-office administration.”

Home infusion of oncolytics “is not a new concept,” he says, and it “offers potential advantages over traditional settings, including but not limited to increased patient comfort and convenience, potential reduced costs and freeing up capacity-limited facilities.” The Oncology Nursing Society and American Society of Clinical Oncology have published joint safety standards for home administration of oncology drugs, and the National Home Infusion Association has a list of more than 350 therapies, including cancer drugs, “to serve as a reference when site-of-care decisions are being considered for IV or SC infusions,” he adds.

However, this approach may receive some pushback from providers, who may lose income, although it ultimately depends on their arrangements with payers. “Payers may reimburse the cost of IV drugs used in clinical settings, and the provider may make margin on the drug product, as well as the professional fees for preparation, administration and monitoring of the drug product, and ancillary supplies,” Szczotka says.

But they already may be losing income when using the SC formulation due to decreased administration fees, points out Higgins. “Health plans could direct and educate patients to alternative care sites in place of hospital-based administration. Like with other treatments in other disease states, providers will discuss treatment options with individuals based on their condition, including the option of using an SC version.”

Ultimately, maintains Szczotka, “providers typically will prescribe the optimal therapy for their patient and the particular situation that will lead to the highest possible patient quality outcome.”

Coverage Is Usually Similar

Higgins and Szczotka say that payers usually are covering the new formulations similar to the original IV version unless there are substantial differences. Szczotka points to a 2022 study of SC rituximab that found “significant cost savings as compared to the IV formulation, as well as increasing provider capacity and freeing patient time. The analyses suggested that the SC administration of rituximab will be cost saving for payers even with a market where biosimilars approach 50% of the product market share.”

Opdivo and Keytruda are widely expected to be up for Medicare drug price negotiation when the Inflation Reduction Act (IRA) expands the program to include Part B drugs next year. The new SC versions, however, will not be subject to negotiation due to their inclusion of hyaluronidase, predict industry experts.

“Payer coverage for Opdivo and Keytruda, as well as other drug products, may modify if the pricing significantly changes under the IRA provisions,” observes Szczotka. “If the price[s] of existing IV therapies are significantly lowered and provide substantial overall cost savings, including factoring in the other associated health care administration costs (i.e., administration and staff costs associated with IV formulations), payers may opt to prefer the overall lower cost therapies if they are able to provide similar clinical, safety and health outcomes.”

Payers will continue covering the drugs, says Higgins, “as both of these medications, even with inclusion under CMS price negotiation, will be key treatment options for individuals with a variety of types of cancers.” She also points out that both Opdivo and Keytruda are expected to face biosimilars in 2028.

Ultimately, contends Szczotka, the decision between an IV and a SC formulation is based on a variety of factors. “The availability of SC administration as an option to deliver oncology treatments is anticipated to reduce caregiver and patient burden and to contribute value and cost savings to the health care system overall. As the U.S. health care system continues to grow and leverage new technology, SC delivery of oncology therapeutics is expected to expand with great potential to improve patient experience, lower the cost of care and help optimize the delivery of care.”

By Angela Maas