A Blueprint for Successful Infliximab Biosimilar Switching

Payers have not been quick to add biosimilar infliximab to their drug coverage. Yet, biosimilar switching is the objective for most health plans and insurers who are thinking about long-term savings. Even if they do not exclude the reference product Remicade® from coverage, some health plans, like Kaiser, have been moving forward in this effort.

At the Academy of Managed Care Pharmacy’s Nexus 2018 meeting in Orlando this week, two clinical pharmacy specialists from Kaiser Foundation Health Plan of the Northwest described what may be a best practice in converting patients to biosimilar Inflectra®.

RELEVANCE OF BIOSIMILAR SWITCHING AT THE PLAN LEVEL

Kayla Hubrich, PharmD, emphasized the importance of patient education, and patients’ reliance on Google for research. She said, “When patients will turn to Google and type in ‘Should I switch to an infliximab biosimilar?’ the first search result they see is an ad for ‘Finely Tuned,’ a Janssen website.” This, of course, discourages the use of biosimilars.

At Kaiser Foundation Health Plans, coverage decisions are made at a national level for its 12.5 million members and implemented at the regional plan level, according to Lynsey Smith, PharmD. The health plan made Zarxio® its preferred filgrastim product in 2016, and registered 96% of all filgrastim dispensings in self-injected settings, and 100% of all clinical administrations for this biosimilar.

Biosimilar switching
Source: Kaiser Foundation Health Plan

Obtaining that level of use means that not only treatment-naive patients were using Inflectra, but also those using Remicade in the past. Dr. Smith outlined the key steps in this conversion, starting with the providers. “For new starts,” said Dr. Smith, “the tactic was just to have the doctor choose the biosimilar” using tools incorporated into the electronic health record that encouraged them to order the preferred product. Concerning those patients needing to be converted from the reference product, Kaiser asked the prescriber to sign a ‘Therapeutic Equivalency Protocol’ agreement, which authorized the plan to make the switch. The biosimilar switching agreement was voluntary, and virtually all the rheumatologists, dermatologists, and gastroenterologists signed. “One GI out of 20 declined to authorize the switch in patients already receiving Remicade,” she said.

Kaiser emphasized patient notification and education. A letter, signed in their doctor’s name, was sent to each patient at least 2 weeks before the conversion date, explained Dr. Smith. Clinical Pharmacy Services was enlisted to answer patients’ questions via phone and E-mail. Patients were also given informational handouts about the biosimilar switching program at their infusion center.

“During this process, the clinical pharmacists received 30 to 40 calls,” she said. “The patients’ main concerns were whether the product was going to work as well as their old drug and whether they would receive the same copay assistance as before.” Active patient outreach was not conducted after the switch was instituted. Any patients reporting issues or concerns were triaged through Clinical Pharmacy Services.

Dr. Hubrich added that infusion center pharmacists reviewed all patients scheduled for infusions one week ahead of their appointment. The infusion center confirmed that the provider signed a TEP document, that patients were sent the notification letter, and that the infliximab order changed to Inflectra. Kaiser also developed a nurses’ protocol for the biosimilar switch and worked to educate practice staff about the program.

 

INFLIXIMAB SWITCHING PROGRAM RESULTS

The conversation program began on May 1, 2017, with dermatologists and rheumatologists, focusing on patients who were getting their first infliximab treatment. Dr. Hubrich stated that notification letters were sent to 158 patients. Three weeks later, current patients began to be switched from Remicade to Inflectra. The GI conversion began on May 11, 2017 with treatment-naïve patients, and letters were sent to 188 adult patients (as Inflectra did not have the pediatric ulcerative colitis indication). Active therapeutic switching began in September. “The one GI who declined to sign the TEP agreement joined in 2018,” said Dr. Hubrich. This is likely because of the experience of this doctor’s peers.

A total of 22 patients (6.4%) across specialties reported adverse events, with nine being changed back to reference product (2.6%), five changed to a different medication class, four resulted in a dosage increase, one patient decided to discontinue therapy, and three continuing biosimilar infliximab treatment without any change. They did find that 12.8% of patients experienced some “nocebo” effects, despite the fact that “no statistically significant changes in effectiveness and safety were observed after a medican of four infusions in 9 months of study.”

Dr. Smith asserted that communication was critical to the success of the program, with patients and providers. The provider’s agreement to sign the TEP document was a necessary step, and was accepted by all Kaiser’s specialist providers.

It must be emphasized that Kaiser has a different magnitude of leverage over its physicians than a network plan like Aetna or CIGNA. Yet a biosimilar switching program like this could be a blueprint for other integrated health plans to move forward if they desire to move patients quickly and efficiently to biosimilar therapy.

Biosimilar Step Therapy for Medicare Part B: Does This Make Sense?

The Centers for Medicare and Medicaid Services (CMS) has decided drugs covered under Medicare part B may be subject to step therapy, if so desired by Medicare Advantage plans. UnitedHealthcare has become the first to publicly implement step therapy policies for these drugs. However, biosimilar step therapy is not the typical utilization management tool that industry executives are used to seeing.

biosimilar step therapyTraditional step therapy or step edits for prior authorization policies are typically used to require the use of an effective, low-cost drug class before trying a more-expensive treatment. For example, a plan might have a step in place before a patient can receive Humira®, such as requiring documented failure on other disease-modifying anti-rheumatic drugs, like azathioprine or methotrexate. This makes very good sense when supported by practice guidelines or treatment pathways, based on solid supportive evidence.

For biosimilar manufacturers, the perspective on the revised CMS policy, seems to imply trying the biosimilar before receiving the branded originator product. This biosimilar step therapy would make very little sense. A doctor would not be practicing evidence-based medicine if he or she prescribed Remicade® to a patient after failure of Renflexis®. There is no evidence to show that the biosimilar will work in a patient who did not receive adequate clinical benefit from the reference product (and vice versa). Similarly, there is no information to show that a patient who has an adverse effect while taking Remicade will not have that adverse effect after injecting with Renflexis (or vice versa). In other words, after failing one, a new mechanism of action should be tried, not a product with a very similar structure. This may be a different argument, if a subcutaneous form of infliximab was introduced, and this might be reason to step the infusible form through this drug.

In United’s announcement, they are clearly seeking to increase biosimilar utilization, as designated preferred part B agents, at the expense of Remicade use, the nonpreferred agent. Therefore, it may make more sense that new patients will have to use a biosimilar before being prescribed the reference product. Step therapy in this case is almost an aside.

Ironically, the Department of Health and Human Services has also expressed its desire to move part B agents like self-administered injectables to part D. This may not apply to infliximab, as it is given as an in-office infusion. Should this be the case, plans will have many pharmacy tools at their disposal beyond biosimilar step therapy.

In other biosimilar news…Fresenius Kabi has signed an agreement with Abbvie to delay its adalimumab biosimilar market entry in the US until 2023. The manufacturer is currently trying to secure European approval for the product. A 351(k) application has not yet been filed by Fresenius in the US.

Pfizer’s Anticompetitive Suit: A Slippery Slope to Competitive Bidding?

When Pfizer first announced its lawsuit against Janssen’s parent Johnson & Johnson in September 2017, it pointed to exclusionary contracting, “anticompetitive” behavior of Remicade®’s maker as the reason for its very limited market access.

The lawsuit claimed that Janssen has withheld or threatened to withhold rebates if payers do not keep Remicade in an exclusive preferred position. The degree to which health plans knuckled under to these demands may only be inferred from the 3% marketshare Pfizer’s Inflectra® now holds. For these drugs, which are still typically covered under the medical benefit, “nonpreferred positioning” usually means no coverage. For drugs covered under the pharmacy benefit, this is not the case.

In August, the Eastern Court of Pennsylvania ruled against J&J in its request that the lawsuit be dismissed. While discovery in the case may be ongoing, we could not find mention of a resolution date for the suit.exclusionary contracting

For the sake of argument, let’s say that the Eastern Court of Pennsylvania rules in favor of Janssen. In other words, exclusionary contracting was not an anticompetitive behavior. That means the status quo is intact, but some factors may affect this situation going forward. These include the Center for Medicare and Medicaid Services’ desire to move part B drugs (the medical benefit) to part D (the pharmacy benefit) for Medicare beneficiaries.

The scrutiny on rebate contracting coming from several sectors, and lack of transparency, may also independently influence future use of these pharmaceutical company tactics. I helped conduct a market research project recently on a nonspecialty drug. As part of these interviews, we were asked by the client to inquire about the range of rebates they were receiving from competitor manufacturers. Their responses were requested as a range (e.g., 20% to 30%), not specific contract details, and we had no intention of providing reports of individual payer deals, only anonymous, aggregate information. We expected little to no response to that query, and that is exclusionary contractingexactly what we received.

Let’s discuss the other potential outcome, in which the Court rules in favor of Pfizer. That implies that this exclusionary contracting practice is indeed anticompetitive. If this is the case, we may be on a very slippery slope. What is the difference between payers and pharma companies engaging in a “1 of 1” contract when there are multiple potential products and a “1 of 2” contract? In both cases, drug makers are committing payers to anticompetitive behavior (as perhaps defined by the Court’s new precedent).

The preferred drug tier (whether preferred generics, preferred brands or whatever) is supposed to be for products with proven clinical, patient care, or economic advantages. Truthfully, payers rarely place medications in the preferred tier for reasons other than net costs or rebate contracting, which is based on marketshare.

Now add in the potential effects of the Administration’s desired shift to part D, where pharmacy benefit rules can be applied. That exposes injectable products that were shielded under Medicare part B to commonly applied formulary placement practices.

To be complete, Janssen’s strategy was not solely based on Remicade. It may be found to have bundled Remicade with other agents in deals to exclude Pfizer’s products. The Court may also react specifically to Janssen’s contract stipulation that threatens to withhold rebates connected to future use of the product, to increase its leverage.

However, if the Court determines that 1 of 1 or exclusionary contracting with rebates are the root of the anticompetitive behavior, why should 1 of 2 or even 1 of 3 contracts in a drug category with 5 similar agents be less so? This is the slippery slope that could undo rebate contracting, and push us towards a system that more resembles a competitive bidding process like in Europe. Alternatively, it could accelerate the move towards outcomes- and value-based contracting. The result could be a system-wide revamping of the drug formulary and the pharmacy–drug maker relationship.

In other biosimilar news…Sandoz has signed a licensing agreement with Abbvie, allowing it to market its biosimilar version of Humira in 2023. The agreement, as with Abbvie’s settlements with other biosimilar makers, halts all patent litigation with Sandoz in exchange for a licensing royalty paid to Abbvie.

Infliximab Biosimilars Savings Could Exceed $400 Million Dollars Annually

Everyone with an opinion believes that biosimilar drug use will save the health system considerable money. Calculations for biosimilar savings have been hampered by several factors. For example, previous high estimates have not been based on real-life scenarios. Only 3 biosimilars have been launched and utilized in the US; so little experience has been gained on which to base calculations.

Yet, isolating the savings associated with a single approved biosimilar does put their potential into perspective. It also demonstrates the promise of cumulative biosimilar savings with their launch and uptake. Based on current infliximab average sales prices (ASPs), wBiosimilar Savingshich considers discounts and rebates, one organization believes that a 50% marketshare for biosimilar infliximab could result in well over $400 million in annual savings system wide.

The analysis, conducted by Wayne H. Winegarden, PhD, Senior Fellow in Business and Economics, Pacific Research Institute, accrued the lion’s share of the annual savings to employer-sponsored health plans ($262 million to $315 million, compared with no sales of infliximab biosimilars). Medicare accounted for up to $150 million savings annually.

Dr. Winegarden tested several scenarios. The calculation considered the cost of the infliximab regimen based its various indications. He calculated biosimilar savings using different add-on percentages to ASP (including the current ASP + 4.3% payment and up to ASP + 20%), as well as different marketshares of the biosimilars (from 10% to 90%).

The current marketshare of the two available infliximab biosimilars—Inflectra® and Renflexis®is below 5%, based on data from the first quarter of this year. This is partly because of Janssen’s tactics in matching the net costs of biosimilars with additional rebates on Remicade. This raises two important points: Dr. Winegarden’s analysis reveals savings accruing to the health care system (not necessarily to the payer). Also, the very existence of infliximab biosimilars has resulted in significant net savings compared with the price increases seen prior to their introduction.

It is a bit more difficult to pinpoint the system savings resulting from the use of the first biosimilar approved in the US, filgrastim-sndz (Zarxio®). The other branded product, tbo-filgrastim (Granix®), was launched a couple of years earlier and gained its own marketshare from the reference brand Neupogen®. No doubt, Zarxio contributed to some level of cost savings. In other words, the infliximab example is an easier calculation with a cleaner result.

With eight biosimilars for six reference products awaiting their turn to hit the market, and drugs like adalimumab and etanercept among them, it is easy to see how biosimilars savings can easily exceed $10 billion. Just not yet.

Is Celltrion Paving a New Road for Biosimilars? A New Route of Administration Being Tested for Infliximab

When payers, patients, or physicians discuss biosimilars, they assume that the biosimilar works just like the reference product. They also assume that the biosimilar is administered in the same way as the originator biologic. Celltrion is actively researching a new subcutaneous infliximab. This could result in a first for the biosimilar industry.

Sponsored by Celltrion and conducted in multiple sites, the research results were announced at the annual meeting of the European Congress of Rheumatology in June. The investigators presented outcomes data on the use of a subcutaneous (SC) form of infliximab-dyyb. Currently, infliximab is only available as an intravenous (IV) infusion at the physician’s office that takes at least 2 hours. Subcutaneous infliximab was given on a biweekly basis.

subcutaneous infliximabThe researchers studied 48 patients with rheumatoid arthritis, finding that outcomes were not clinically different through 30 weeks of follow-up. Three dosages were tested, and in this small study, no ACR20 differences were reported in any subgroup receiving infliximab infusions or SC injections.

Hypersensitivity reactions did occur in one patient each receiving the lowest dose (90 mg) SC and the middle dose (120 mg). None were seen in the group receiving the highest infliximab SC dose (180 mg). Injection site reactions occurred in two patients apiece in the 90 mg and 180 mg dose cohorts. receiving subcutaneous infliximab. The formation of antidrug antibodies was detected in nine patients receiving the standard infusion, but less than half that number in each of the subcutaneous groups.

Currently, infliximab treatment requires a lengthy office visit for each infusion (every 8 wk in the maintenance phase). It is one of the key limiting factors to its use. A self-injectable formulation should result in lower administration costs, and the potential for covering the agent through the pharmacy benefit.

A phase 1, open-label trial of subcutaneous infliximab has already been conducted by Celltrion in patients with Crohn’s disease. That trial found similar outcomes between the SC and IV formulations. Another phase 1 trial is wrapping up, this one evaluating safety and pharmacokinetics in healthy volunteers. Celltrion is also sponsoring a phase 3 trial of more than 300 patients with rheumatoid arthritis. Preliminary results will not be available until December 2018.

It is not yet clear, however, what type of data the Food and Drug Administration would require for approval of a new formulation of a biosimilar. The regulatory agency may decide to treat this as it would a new route of administration for any approved product, which would focus on pharmacokinetic and pharmacology factors. Celltrion seems to be covering all of its bases.

Plans Use Step Therapy to Encourage Utilization of Remicade Over Biosimilars

Health plans and insurers are not yet turning to biosimilar infliximab as a preferred therapy, according to Gillian Woollett, DPhil, MA, of Avalere. Her new report surveyed publicly available policy about health plans across the nation. The principal finding was that step therapy was commonly used  to encourage use of the originator product.

In fact, just one health plan (representing 1% of the 172 million lives covered in this study) supported the use of either Inflectra® or Renflexis® over the reference product Remicade® through step therapy. One plan (2% of the covered lives) allowed the use of either the originator product or Inflectra as a first step.

Gillian Woollett of Avalere on step therapy and biosimilars
Gillian Woollett

Four of the 18 plans with publicly available information did not utilize step-therapy rules for any forms of infliximab. However, “10 of the 18 plans (55% of plans, 52% of covered lives) require the use of [Remicade] first, alone or in combination with another DMARD,” stated Dr. Woollett in the report. A total of 81% of the covered lives from these 18 plans were subject to step therapies limiting access to one infliximab product or the other.

On its face, this type of step policy makes a bit of sense. Step therapies are often used alone or part of prior authorization mechanisms to make sure patients try more cost-effective agents first. In rheumatoid arthritis, that may comprise use of nonbiologic drugs before proceeding to a TNF inhibitor and then to another biologic in patients with rheumatoid arthritis. However, there is no proven benefit (or even logic) to offering a biosimilar infliximab after failing Remicade, or vice versa. If there was a significant clinically relevant difference in immunogenicity, this could be an issue, but this also has not been seen in practice. It makes more sense to try another anti-TNF or perhaps even move to an interleukin inhibitor—something with a different (or slightly different) mode of action.

A policy such as this can confuse the issue for patients, whose knowledge of biosimilars seems tenuous, and even providers, some of whom have little experience prescribing them, particularly because of payers’ Remicade-first policies.

The Avalere report provides some support for how payers are arresting utilization of biosimilar infliximab in favor of the originator infliximab product.

Dr. Woollett paints a very different picture for subcutaneously administered filgrastim products. Forty-nine percent of the covered lives (five large plans) had policies favoring Zarxio®, whereas 27% of covered lives were encouraged to use Neupogen® first.  For these 18 plans, five (28% of plans, 49% of covered lives) demonstrate a preference for the biosimilar, filgrastim-sndz. Five (28% of plans, 27% of covered lives) demonstrate a preference for the reference filgrastim. Eight plans (44% of plans, 24% of covered lives) do not indicate a preference through formulary design. A further 24% were not subject to any preference.

Pfizer’s At-Risk Launch of Inflectra Pays Off (at Least a Bit)

The US Court of Appeals handed Pfizer a big victory in its gamble to bring its biosimilar version of Remicade® to the market before the completion of patent litigation. On January 23, the Appeals Court ruled that Johnson & Johnson’s ‘471 patent in the case was declared invalid, clearing the way for sales of Inflectra® (infliximab-dyyb). Had Pfizer lost the suit, J&J could have sought Inflectra’s (and Samsung/Merck’s Renflexis®’s) revenues in addition to other damage claims.

Remicade’s ‘471 patent expiration was September 2018, but the US Patent and Trademark Office earlier ruling contended that the antibodies at the center of this patent were already included in patents that had previously expired.

Remicade is manufactured and sold by J&J’s subsidiary, Janssen Biotech.

In a widely publicized case, Pfizer sued J&J in September 2017 for anticompetitive practices, which it believes held down the sales of Inflectra to a spare $74 million for the first three quarters of last year. Although J&J is seeking to appeal the decision, with the patent expiration date looming, as well as limited sales of Inflectra, this would seem to be of relatively little benefit.

In any case, J&J is wary of losing marketshare and revenues on Remicade. According to Bloomberg News, Janssen Biotech saw fourth-quarter revenues from the biologic drop almost 10%, to $1.47 billion. Increasing competition from other biologics for similar indications and other biosimilar versions of infliximab worldwide have contributed to reduced sales.

A Pre-Holiday Gift for Pfizer—a Second Infliximab Biosimilar Approval. Now What?

On December 14, Pfizer got an early Christmas present, the approval by the Food and Drug Administration (FDA) of the second infliximab biosimilar in which it has a stake. First came Inflectra® in 2016, and here comes Ixifi™ (infliximab-qbtx). Unlike Inflectra, which Pfizer markets for Celltrion, Ixifi is Pfizer’s alone—Web image for headera product that was under development at the time of the acquisition.

This of course puts Pfizer in an interesting position. Ixifi would be the third infliximab biosimilar to reach the market, after Inflectra and Samsung/Merck’s Renflexis™. True, Inflectra has limited marketshare in the US, and competition from more heavily discounted Renflexis could compound the situation.

It seems that Ixifi is not intended to reach the US market at all, and may be marketed in other countries where the Celltrion agreement does not hold sway. However, this begs the question: Why did Pfizer decide to go apply for a 351(k) application for FDA approval? That is unclear at this time. Perhaps they will use this biosimilar as insurance if Inflectra does not perform as promised. On the other hand, Pfizer could license it to another manufacturer and collect additional royalties from its sales in the US and overseas.

For those of you who guessed the last choice, congratulations! Under a deal signed in early 2016, Sandoz obtained the rights to market this agent in the European Economic Area. This would enable Pfizer to earn cash rewards and other prizes from two biologics in the same biosimilar category.

Pfizer Sues J&J on Anticompetitive Practices on Infliximab in the US

In late May, Merck was named in a UK lawsuit by Pfizer, which has been trying to expand its market for Inflectra®. Merck, which markets Remicade® (infliximab) in the EU, was accused of anticompetitive practices. On September 20, Pfizer brought a similar complaint against Johnson & Johnson (the parent of Janssen and the manufacturer of Remicade®) in the US, according to a lawsuit filed in US District Court (Eastern District of Pennsylvania).

Whereas Pfizer has made some inroads to the US market, since its launch at the end of 2016, Janssen has done a good job of blocking and tackling—playing the contracting game. The lawsuit claims that Janssen has withheld or threatened to withhold rebates if payers do not keep Remicade in an exclusive preferred position. Pfizer may have invited such action to an extent by entering the market at a 15% discount to the originator’s wholesale acquisition cost (WAC). Many experts expected this type of approach by Janssen. Payers were candid in their reluctance to switch to the biosimilar, especially if Janssen would counter the modest discount with rebates that narrow or eliminate the difference in net costs. In other words, a greater discounted price may have opened the market to Pfizer more rapidly, because Janssen may have been less aggressive in its efforts to match the net cost.

In an August earnings call, Pfizer indicated that although Medicare is covering Inflectra, its overall US marketshare was only 2.3%.

According to the press release announcing Pfizer’s lawsuit, “[Johnson & Johnson’s] exclusionary contracts and other anticompetitive practices have denied U.S. patients access to therapeutic options and undermined the benefits of robust price competition in the innovative and growing biologics marketplace for patients… J&J’s systematic efforts to maintain its monopoly in connection with Remicade® (infliximab) by inappropriately excluding biosimilar competitors violates federal antitrust laws and undermines the principal goals of the federal Biologics Price Competition and Innovation Act (BPCIA).”

This may be the first time that routine contracting efforts to defend against generic competition and maintain a monopoly within a drug category have been cited as a violation of antitrust legislation. What may have amplified Pfizer’s ire was its assertion that several insurers originally placed Inflectra at parity coverage with Remicade. These payers changed their position after “J&J threatened to withhold significant rebates unless insurers agreed to effectively block coverage for Inflectra and other infliximab biosimilars.”

Furthermore, the suit claims that clinicians and hospitals were reluctant to purchase Inflectra, with the belief that insurers may not reimburse them for its use. These providers may have been further influenced by an insistence by J&J on their signing contracts that dictated significant discounts on Remicade only if they would not purchase Remicade or other infliximab biosimilars.

At this time, Inflectra is priced at an average 19% discount to Remicade’s wholesale acquisition cost (WAC). Pfizer says that it is offering additional discounts on top of this to persuade payers into covering their biosimilar. Merck’s launch of its own biosimilar infliximab (Renflexis®) comes with a price tag of 35% below that of Remicade, which adds tremendous pressure on payers to reconsider their positions. This also signals the early closing of Pfizer’s window of opportunity as the first biosimilar entrant, on which it gambled an at-risk launch.

The Week in Biosimilar News

You know it’s been a pretty desperate week in the biosimilar blogosphere when twitter feeds relate back to articles published in January, rehashes of the US Supreme Court decision in June, or yet another estimate of the savings potentially ascribed to biosimilar use (based on erroneous assumptions). However, there were a few significant tidbits announced last week that are worth reviewing.

First, Biocon announced that the decision to approve its trastuzumab biosimilar (with partner Mylan) has been delayed by the Food and Drug Administration (FDA) 3 months (until December 3, 2017). According to Biocon, this delay was required so that the FDA could “review some of the clarificatory information submitted as part of the application review process.” Clarificatory? Really? Maybe the extra time was needed to translate the application itself.

Second, a survey of 103 US gastroenterologists raised a couple of questions as to how well information about Inflectra®, the biosimilar to Remicade®, is sinking in on the practice level. According to a press release from Spherix Global Insights, cross-category prescribing may be interfering with the uptake of the biosimilar. They state, “not only is the decline [in Remicade prescriptions] attributed to the adoption of infliximab biosimilars, but use of Humira® has also significantly increased, potentially indicating that more ulcerative colitis patients are being placed on Humira to avoid insurance mandates for infliximab biosimilar use.” This limited survey found that more than one-third of gastroenterologists “agree that if a pharmacy or managed care plan advises them to use Inflectra over Remicade, that they are more likely to choose a different TNF-inhibitor altogether.” This is a weird finding, perhaps indicating nothing more than spite for the health plan’s benefit design. Clearly, if the physicians fully considered the evidence, they would be less likely to prescribe in this way. Admittedly, as notable numbers of managed care organizations have not actually mandated Inflectra use at this point in time, we would have to wait to see if this opinion is validated in actual practice.

Finally, Sanofi announced that it had received tentative approval on a follow-on biologic form of insulin lispro (the originator product was Lilly’s Humalog®). Patent issues will have to be resolved before Sanofi can receive final approval and bring this product to the market. The insulin biosimilars are not regulated under the Biologics Price Competition and Innovation Act, but rather under the Hatch–Waxman Act—the application was filed as a 505(b)2 rather than a 351(k) variety. They are transitional products, which will considered under the newer regulations after March 23, 2020. We will detail these lesser-known transitional drug categories in a future post.