Samsung Bioepis Signals a Settlement With Genentech on Herceptin Biosimilar

And then there was one. Samsung Bioepis and Genentech filed a motion in District Court to drop all pending patent litigation regarding Ontruzant®, an approved Herceptin® biosimilar. A Joint Stipulation of Dismissal is usually the confirmation that a licensing agreement has been reached.

This leaves one remaining approved trastuzumab biosimilar maker that has not settled with Genentech (a subsidiary of Roche). Amgen’s product Kanjinti®, which was the last trastuzumab biosimilar approved (in June), is the last of 5 approved agents that is not yet subject to a Genentech agreement. The other manufacturers, Mylan/Biocon, Teva/Celltrion, Pfizer, and now Samsung Bioepis, will likely pay a royalty to Genentech whenever their products are launched.

Launch dates have not been announced (nor have the terms of these agreements) for any Herceptin biosimilar. However, the principal patent for Herceptin® has expired, so biosimilar competition should be available before the end of the year.

In other biosimilar news…Coherus Biosciences announced that it has manufactured its 400,000th dose of its pegfilgrastim biosimilar Udenyca®. Additionally, its unaudited second quarter earnings seem to indicate positive movement, as much as $84 million (more than doubling first-quarter earnings of $37 million).

Trump Administration Does About-Face on Drug Rebate Safe Harbors: Opportunity Lost for Biosimilar Competition

It seemed like the best opportunity biosimilar manufacturers had in a long time to gain a competitive foothold upon launch. Secretary of Health and Human Services Alex Azar had promised a repeal of the drug rebate safe harbor as a key component of the Trump Administration’s move to obtain lower drug prices. Today, the Administration reversed its course, leaving the biosimilar industry hanging in the balance.

drug rebate safe harbor
HHS Secretary Alex Azar

According to reports, Health and Human Services found itself between a rock and a hard place. If the drug rebate safe harbor was removed, Medicare part D premiums could rise (plans would compensate for lost rebate revenue by raising consumer costs). There was also no guarantee that lower prices would be passed on to consumers at the pharmacy. Loss of drug rebates would also place great pressure on pharmacy benefit managers (PBMs) to maintain or reduce net drug costs for their plan and employer clients. Accordingly, the removal of the drug rebate safe harbor was opposed by many stakeholders and not supported by enough interests (or with sufficiently influential lobbyists).

The result is a critical missed opportunity for increased access to biosimilars and their attendant savings. Drug rebates can only have value for payers if marketshare exists. In other words, a reference drug manufacturer who holds 100% marketshare before biosimilar launch can offer rebates on every prescription filled—that adds up to millions of dollars for individual PBMs and plans. A biosimilar drug without any marketshare at launch can offer a 50% rebate, but this is meaningless to the payer unless it captures significant marketshare immediately. Without rebates in the equation, biosimilars can compete against reference products on price alone, a much fairer fight for a new drug entering the fray.

Thus, the “rebate trap” will remain a barrier to access. This episode also makes one wonder which trial balloons given flight by the Administration will not come back to Earth. The idea of using the Federal Trade Commission to cut through patent thickets was recently floated and shot down by Texas Senator John Cornyn on the Senate Judiciary committee. We’ve heard about the plan to pin Medicare drug prices to either an international price index or to “most favored nations” pricing, or perhaps even both? Improving the utility of the Purple Book, to actually include useful information about key patent expirations and market exclusivity periods seems simple enough, but even this will take some doing. Interchangeability guidelines published in final form? Well, that should have been completed a couple of years ago.

Despite the approval of 21 biosimilars in the US, the industry does seem to be an awful lot to be worried about. Add in the looming concern in federal appeals court about whether the Affordable Care Act can withstand ongoing attacks concerning the individual mandate, which can then undercut the entire regulatory pathway for biosimilar approval. I know I’m not the only person shaking his or her head. The repeal of the drug rebate safe harbor was a real opportunity to turn the tide.

A Profile on Lesser-Known Player in the Biosimilar Space: Formycon AG

On occasion, we profile some biosimilar manufacturers about whom our readers may not be as familiar as the large players like Sandoz, Amgen, and Pfizer. This generally refers to companies that have products that are in earlier-stage research or those who simply have not been in the news as often as their colleagues. In this updated post, we highlight a German company, Formycon AG, which has eyes on the US marketplace.

Formycon acquired Scil Technology GmbH in 2012, and hired a new CEO the following year. Carsten Brockmeyer, PhD, has extensive experience in the biosimilar field, previously helping Hexal Biotech to develop EPO and filgrastim biosimilars for the European market.

Why you may be hearing more about this company: Formycon has two principal biosimilar targets, ranibizumab and ustekinumab. The company disclosed that “it successfully completed a Type IV pre-submission meeting with the US Food and Drug Administration (FDA) in December 2018 and clarified other pivotal issues. The filing with the FDA for the approval of FYB201 is expected at the beginning of the fourth quarter of this year.” A filing for the European Medicines Agency is planned for 2020. A phase 3 clinical trial of this agent was completed in June 2018. In the development of this agent, Formycon partnered with Bioeq GmbH, but it is unclear whether a marketing partner exists for a possible US launch.

The patent for ustekinumab (Stelara®) expires in 2023 (US) and 2024 (Europe). It is partnered with Aristo Pharma GmbH on the manufacture and testing of this interleukin 12/23 inhibitor (also known as FYB 202).

Formycon is in the early stages of developing a phase 3 trial for its biosimilar version of Eylea® (aflibercept or FYB 203), the next generation of macular degeneration treatment. It is partnered with Santo Holding GmbH on the development of aflibercept.

In other biosimilar news… Amgen decided to pull its EMA application for its infliximab biosimilar, likely due to market competition. The company has not taken similar action with regard to an FDA application for the same product, ABP 710. Considering that neither Samsung Bioepis or Pfizer failed to gain traction in the US marketplace for infliximab, Amgen must think that some biosimilar infliximab marketshare growth in the US is still possible.

$7.6 Billion Estimate on Savings Lost From Approved, Nonlaunched Biosimilars Could Be Low

$44 Billion by 2024. $250 Billion by 2024. Whatever. I’ve not been very impressed by the many attempts to estimate how much money biosimilars could save the US health care system. Even the more well-known estimates of biosimilar savings, like those from RAND and Express Scripts, have been little more than games of “pin the tail on the donkey,” as the researchers were blinded as to when products would actually launch and the unproved potential for biosimilar uptake.

Of course, this was not the economists’ fault. They had little past information about the US biosimilars market on which to base their view of the future, and they could not have predicted the extent to which patent litigation prevented access to these medications.

I do appreciate the latest effort, however, by the Biosimilars Council (a subsidiary of the Association for Accessible Medicines) to understand biosimilar savings. Instead of predicting the future, the Council reviewed the past to assess how much each biosimilar would have saved the health care system and patients had they launched as expected.

The number they landed on was $7.6 billion since the introduction of the first biosimilar in 2015 through 2018. It applies not to the seven biosimilars (as of June 12, 2019) that were launched but to the 12 that were approved but not available because of ongoing patent litigation.

As impressive as this lost opportunity sounds, I believe that the biosimilar savings estimate is still too low. The calculation by the Biosimilars Council does not seem to include an important aspect: The reference manufacturer takes significant price annually for each year biosimilar competition does not emerge. The analysis assumed a 30% price discount and 40% uptake, split between two biosimilar competitors. Uptake was assumed to increase to 50% if three were three separate competitors. Yet the analysis was based on actual list prices from IQVIA data.

If biosimilar competition existed, these price increases would not have occurred, likely at all. For example, the availability of Inflectra® and Reflexis® did not fuel great uptake of biosimilars at the expense of Remicade®; however, the infliximab market was changed suddenly, by forcing Janssen Biotech to not only halt their price increases in 2016 but significantly lower their net pricing. As a result, average sales prices have been dropping ever since the introduction of the biosimilars (from a high of $85.81 per 10 mg in January 2018 to $69.96 in July 2019 [–19%]).

Consider the same scenario for the adalimumab biosimilars, which I wrote about previously. Without competition, AbbVie can raise its retail prices right through 2022, resulting in upwards of 50% higher list prices. Although this does not account for contracting, each new payer contract it should be remembered, is based on the current price (not the previously rebated costs). In other words, the higher prices work their way into subsequent payer contracts. How much additional biosimilar savings, on top of the calculated $7.6 billion, would that be? I’m not an economist, but it shouldn’t be too difficult to estimate, based on no future price increases (only future price reductions). Over an 18-month period, Amgen raised the price of Enbrel® four times, resulting in a 37% jump by 2016. Had biosimilar etanercept been available at the time, that would not have happened, yielding an instant 37% savings. That does not prevent the reference manufacturer from hiking the drug price in the months before biosimilar competition occurs. This practice is expected to continue. However, the earliest possible availability of biosimilars will yield compounded price savings.

Even in Europe, Biosimilar Uptake Depends on MD Comfort Levels

Sometime ago, the European Crohn’s and Colitis Organization (ECCO) found that sequential surveys had demonstrated improving physician comfort with prescribing biosimilar infliximab. This resulted in ECCO’s change in its position on switching infliximab. As one can imagine, this occurs only with experience, and often that experience is gained first by using the drugs in new patients only.

According to Ha Kung Wong, Partner, Venable LLP, physician comfort and education is still the primary determinant of biosimilar uptake, even in Europe. In his remarks at the recent ACI Biosimilar Summit in New York City, Mr. Wong emphasized that although price will enable a biosimilar to gain a foothold, it is not the only or most important factor. This is somewhat surprising; the competitive tendering system in many countries have resulted in significant price variation, including steep discounts in some locations.

Ha Kung Wong
Ha Kung Wong

Mr. Wong explained that in Norway and Denmark, Remsima uptake has risen through deep discounts, though in other countries, discounts were far less extreme. On the other hand, less variation has been seen with trastuzumab pricing. Mr. Wong said, “Regardless, the uptake of biosimilars has been quite high across the EU. For example, Samsung’s Imraldi reached 60% uptake in Germany after only a very short time.”

He pointed out that “price does increase marketshare. But growth in uptake is still driven by biosimilar use in new patients.” Ha Kung Wong said that even in the EU, resistance to switching patients from a reference product to a biosimilar continues.

“The number 1 factor is MD resistance to switching,” he stated, although patient resistance is also apparent. Considering the heavy involvement of EU countries in educating doctors and patients with regard to biosimilars, more needs to be done if systematic switching of patients to biosimilars will contribute more fully to the industry’s success.

This experience in Europe is extremely pertinent to the situation in the US. Physicians are beset by costly administrative efforts to meet payers’ prior authorization and step edit requirements, and they may be also less experienced in the prescribing of biosimilars than their European colleagues. If the relative value of the biosimilar is not substantial enough, expect that prescriber uptake will grow only slowly. Consider not necessarily the case of infliximab, but the newest categories to likely hit the market—the biosimilars for the treatment of cancer (e.g., trastuzumab and bevacizumab). These prescribers will need some time to become comfortable with treating their vulnerable patients with biosimilars, and the requirement for use in “new” patients may not apply. It would be feasible to switch cancer treatment after completion of any cycle, as well as for recurrent tumors.

Introducing the 21st FDA Approval: Pfizer’s Zirabev, a Biosimilar of Avastin

On June 28, 2019, Pfizer announced that it had received Food and Drug Administration (FDA) approval of Zirabev™ (bevacizumab-bvzr), a biosimilar version of Roche’s Avastin®.

Pfizer approval of Zirabev

Based on the evidence provided by Pfizer, including its phase 3 trial comparing it to the EU-licensed version of Avastin, the FDA approved Zirabev for five cancer indications, including:

  • Advanced, metastatic, or recurrent nonsquamous non–small cell lung cancer
  • Metastatic colorectal cancer
  • Recurrent glioblastoma
  • Metastatic renal cell carcinoma
  • Metastatic cervical cancer

This approval does not include ovarian cancer, which is an additional indication for Avastin. Belonging to a class of biologics called vascular endothelial growth factor (VEGF) inhibitors, these agents work by preventing new development of a tumor’s blood vessels, helping to choke off growth.

Zirabev’s approval marks the 21st FDA approved biosimilar agent and the second approval for a bevacizumab biosimilar. Mvasi®, to be manufactured by the partnership of Amgen and Allergan, obtained approval in September 2017. However, this product is not yet marketed.

At a recent annual meeting of the Academy of Managed Care Pharmacy, a specialty drug pipeline expert expressed hope that Mvasi would be launched in July of this year. Its manufacturer has been embroiled in patent litigation with Roche, but the key patents are expected to expire in the immediate future.

Pfizer has not announced a launch date for Zirabev. Yet, it could be the second cancer-treating biosimilar category to enter competition (with Herceptin biosimilars) very shortly.

Dancing With the Stars, Patent Style

In June 2017, the US Supreme Court ruled that the “patent dance” was not mandatory for biosimilar manufacturers. Since then, our discussion of the patent dance (not patent litigation) has been infrequent. The first wave of biosimilars tended to perform the dance (or did it not incompletely). Therefore, manufacturers of drugs like filgrastim, infliximab, epoetin, and others have already hit the dance floor or not. The patent litigation that has resulted or been headed off (less likely!) already occurred. Since the Supreme Court ruling, if you will, the music was still playing, but there were fewer spectators.

The patent dance can be mystifying but it can also be rewarding, say patent attorneys at a recent conference in New York City. Judging whether to participate requires several considerations.

I hadn’t given the patent dance much thought since that time. I was under the impression that the majority of developers of new biosimilars would likely now avoid this process.

An excellent session at the ACI Biosimilar Summit this week in New York City focused the spotlight on the dance floor once again. The meeting itself was chockfull of attorneys—attorneys talking patents. Inevitably, this topic resurfaced. And it caused me to alter my perceptions.

CONTROLLING THE INFORMATION EXCHANGE

The exchange of information that takes place upon initiating the patent dance can still be advantageous to the biosimilar maker and the manufacturer of the innovator biologic. Irena Royzman, PhD, Partner at Kramer Levin, explained, “The patent dance gives control to the biosimilar applicant. It limits the number of patents the innovator can litigate. This is very powerful, especially when the innovator has [a multitude of patents].”

However, there could be advantages for the biosimilar applicant who decides not to participate. For instance, she said, the applicant can keep reference manufacturers from knowing what indications are being sought, unless these are released publicly. They can also shield such critical information as the manufacturing process.

TAPPING IN AND TAPPING OUT

Petra Scamborova, PhD, Director, Dispute Resolution, Regeneron Pharmaceuticals, pointed out that participating in the patent dance does not have to be a black and white decision. “There are several options,” Dr. Scamborova remarked, besides fully participating in the patent dance, which she believes is still the best option for biosimilar manufacturers. “It gets you the patent list early on,” she said, “which commits the innovator to asserting a specific set of patents that they will defend. It also gets you the reference manufacturing information prelitigation,” added Dr. Scamborova.

“If the innovator doesn’t abide by the rules of the dance fully,” she continued, the applicant will be at reduced risk, which may result in “a reasonable royalty only” should the biosimilar maker be on the losing end of a district court decision. Dr. Scamborova also commented that full participation in the patent dance avoids unnecessary litigation down the line.

Charles Klein, Partner, Winston & Strawn LLP, offered another option: “dancing partway,” that is, beginning the patent dance but electing to exit the process before completion. He thinks this may be a viable strategy if the reference product’s 12-year exclusivity is already expired. He noted, “It usually takes 6 to 9 months to get through the patent dance prior to litigation.”  If a biosimilar maker intends to launch their product relatively soon after approval, delaying the litigation by 6 to 9 months can have a material effect on its ability to launch (e.g., 2 yr after approval).

However, undergoing the initial dance steps gains some of the important information during the exchange. “If you elect not to continue the dance,” Mr. Klein said, “the downside is that the biosimilar applicant loses control over the litigation. The sponsor could decide not to sue immediately (though not likely), which will delay resolution. You will also waive the statutory limitations on remedies.”

From the innovator’s perspective, a partial dance is better than no dance at all, Mr. Klein stated, “because you get a good deal of information from the applicant’s application. You control which patents to assert and when to assert them.”

GETTING IN AND OUT OF STEP, DEPENDING ON TIMING

What about option 3—no dance at all? The attorneys on the panel believe that decision again hinges on the timing of the 12-year exclusivity. Matthew Pearson, Partner at Akins Gump Strauss Hauer & Feld, pointed out that avoiding the patent dance altogether may be a good choice if, for instance, the applicant is not the first biosimilar for the innovator drug. “You may think you already know what patents will be asserted by the innovator.” In this scenario, the biosimilar applicant can keep its manufacturing information from the innovator company for some time.

Another important factor in deciding whether to engage in the patent dance relates to the new biosimilar maker’s belief as to whether it will infringe the innovator’s patents. If the biosimilar manufacturer believes it they will not infringe, and it does not have the first biosimilar for a particular biologic, he thinks it may make sense to avoid the patent dance completely.  

What of the scenario when the opposite is true, where the biosimilar maker is faced with 70 patents and expects to infringe on some? The patent dance can then limit the number of patents that can be litigated. In the case of fewer potential patents at issue, the attorneys on the panel believe that the launch timing will play a role (along with the biosimilar maker’s willingness to accept risk). If sufficient time exists before potential launch, proceeding to the dance floor would make sense, they said.

Finally, in the case where the applicant knows only partially which patents will be asserted, but assumes it will not infringe upon any of these. Then, beginning the patent dance makes sense; the biosimilar maker can obtain the list of patents to be defended by the reference drug maker. It might then also make sense to stop the dance after confirming the patent list. Overall, they claim, the patent dance does present some benefits for biosimilar developers. The Supreme Court’s opinion did not strike down the process, only the fact that it was not mandatory. Based on the opinions of these experts in the process, it make still help smooth a still rough path through the litigation process.

Don’t Expect All-Out Biosimilar Competition for Herceptin—Just Yet

Five trastuzumab biosimilars have been approved for marketing in the US, and the composition-of-matter patent for the reference product, Herceptin®, expires June 30, 2019. That doesn’t mean we’ll see a jail break of competition, like that seen in the EU last October with adalimumab’s patent expiration. Yet there has been heavy interest in capturing a slice of Herceptin’s $2.9 billion US sales (in 2018).

Three manufacturers have signed licensing agreements with Genentech (subsidiary of Roche). In March 2017, Mylan signed the first agreement for its product Ogivri®. Its marketing partner is Biocon. In December 2018, Pfizer followed suit for its recently approved agent Trazimera®. None of the parties have indicated when a biosimilar agent will be launched. At the end of December, Celltrion and Teva came to a similar agreement on its Herzuma® biosimilar.

Herceptin patent litigation

According to Goodwin’s Big Molecule Watch, Roche’s infringement claims against Samsung Bioepis (Ontrusant®) and Amgen/Allergan (Kanjinti®) are still being litigated. For Genentech v. Samsung, the bench trial is slated to begin December 9, 2019. In addition, Samsung Bioepis is appealing the Patent Trial and Appeals Board ruling regarding the validity of Herceptin’s method of use patents. Separately, Genentech is challenging the PTAB’s decision that two other Herceptin patents were invalid. There’s a whole lot here that needs to be resolved (or settled).

In the case of Amgen and Allergan, Genentech originally brought suit claiming 38 patents were infringed (in June 2018). In July 2018, Genentech reduced this figure to less than half (17). A month later, Amgen responded to the suit. Little information is available on timing of next steps.

Based on this information, it is difficult to know just when the first trastuzumab biosimilars will be launched. If Genentech followed Abbvie’s example in its 2023 sequencing of adalimumab biosimilars, one might expect Mylan’s product to be available first, perhaps as early as this summer, with Pfizer’s and Celltrion to follow perhaps six months later.

Yet, unlike the Abbvie agreements, none of the Genentech licensing settlements were made public (other than the actual dates of the agreement). Keep in mind, Herceptin was first approved by the FDA in October 1998. In 2018, the drug’s sales in the US and EU combined was over $4.7 billion. Is 21 years of market exclusivity to anyone’s benefit, other than the manufacturer? Since 2006, US drug sales of Herceptin have been greater than $1 billion annually. If the biosimilar launches do not occur shortly, this may be a good test case of the Federal Trade Commission’s commitment to clearing patents in the name of competition.

Amgen/Allergan Announce FDA Approval of Their Trastuzumab Biosimilar

On June 13, the Food and Drug Administration (FDA) approved the fifth trastuzumab biosimilar. This product, Kanjinti (trastuzumab-anns), will be produced through the partnership of Amgen and Allergan.

Originally filed in July 31, 2017, the drug makers received a complete response letter June 1, 2018. Their resubmission resulted in the approval for all indications of the reference product Herceptin®, including:

  • Treatment of HER2-overexpressing breast cancer (in adjuvant nonmetastatic and metastatic settings)
  • Treatment of HER2-overexpressing metastatic gastric or gastroesophageal junction adenocarcinoma.

This trastuzumab biosimilar is approved for use in combination with other specific cancer chemotherapy or as monotherapy. The Kanjinti approval was supported by four open-label clinical trials in over 10,500 women with breast cancer.

Kanjinti was approved by the European Marketing Agency on May 30, 2018 (and is marketed under the Kanjinti name).

No announcement was made as to when Kanjinti will be marketed in the US. None of the other trastuzumab biosimilars are currently available in the US; however, its principal patent expires at the end of June. This should open the door for immediate and aggressive price discounts on both the reference product and its 5 biosimilars for the $2.9 billion US market. No licensing agreements have been announced for Herceptin biosimilars.

This marks the second biosimilar approval for partners Amgen and Allergan. Their bevacizumab biosimilar (Mvasi®) won approval in 2017 and is not yet marketed.  

Limited Interest in Insulin at Shown by Biosimilar Makers

The importance of insulin competition cannot be overemphasized today. Prices for each types of insulin have lurched upwards. The first competitive version of insulin glargine was approved in the US in late 2015, and according to IQVIA data, it has gained 31% of the US market (as of Q4 2018). Yet, information on other types of insulin to be approved as biosimilar under development is very limited at the moment.

Insulin in Transition

Part of the reason may be the transitional nature of insulin approval. In March 2020, all follow-on insulin “copies” must be approved under Section 351(k) of the Public Health Act, rather than under 505(b)(2) of the Food, Drug & Cosmetics Act. All three approved follow-on insulins in the US (Basaglar®, Lusduna®, and Admelog®) entered the market as 505(b)(2) agents. Lusduna is no longer being marketed in the US by Merck because of limited revenue potential. This decision may have been influenced by the closer federal scrutiny on insulin price increases of late.

Some development is ongoing for new insulin competition, but these are currently limited to insulin glargine, vying for a slice of the Lantus® market. Mylan, Sandoz, and GC Pharma all have biosimilar insulins that have been approved elsewhere in the world, Mylan and Biocon had first applied for FDA approval through the 505(b)(2) pathway in September 2017; they received a rejection due to manufacturing plant problems in June 2018. Current details are not known. Admelog® remains the only follow-on version of insulin lispro available or in development. Any FDA filing that remains unapproved by the transition date will be converted to a 351(k) biologic licensing application, subject to an entirely different level of requirements. It may be that prospective biosimilar insulin makers are awaiting the passage of the transition date before beginning the FDA filing process.

BR&R requested information from the FDA as to the number of biosimilar insulin clinical development programs currently in their system. A spokesperson for the FDA’s Center for Drug Evaluation said they couldn’t disclose any information about current biosimilar clinical development programs (event the number). Without this information, the chart below was based on publicly available information, and this is thin indeed, considering the various forms of rapid and intermediate-acting insulins that will be subject to biosimilar competition.

TABLE: INSULIN VERSIONS CURRENTLY APPROVED OR UNDER DEVELOPMENT

Company Insulin Type Brand name Status
Sanofi Aventis Insulin lispro Admelog  Approved by the FDA, Dec 2017, marketed
Samsung Bioepis/Merck Insulin glargine Lusduna Approved by the FDA, withdrawn in Oct 2018
Lilly Insulin glargine Basaglar Approved by the FDA, Dec 2015, marketed
Mylan/Biocon Insulin glargine   Approved in EU and Australia March 2018; 505(b)(2) application rejected June 1, 2018
GC Pharma Insulin glargine   Launched in South Korea Nov 2018
Sandoz Insulin glargine   Signed agreement with the Chinese company Gan and Lee to supply Sandoz with insulin
Lannet Insulin glargine   Phase 1 trial ongoing
Data gathered from multiple sources. 

The Insulin Authorized Generic

Also of direct impact to potential biologic makers, is the action taken by Lilly recently, when it launched a 50% price cut for its popular Humalog brand, under the banner of an “authorized generic.” This enabled Lilly to continue selling its Humalog brand, while getting a jump on the lower-cost market as a separate generic. This raises another separate interesting point: If Lilly outsources the production of the lower-cost version of Humalog, does this not imply that it is subject high risk of lot-to-lot variation? This is an issue at the heart of biosimilarity. Yet, the product is still covered by the FD&C Act; can this insulin version still be construed as a generic? On the other hand, if Lilly manufacturers this agent itself, since the molecule is the same as the brand, by the same manufacturer, a generic characterization of this biologic may still be possible. We digress….

For long-time insulin makers like Lilly, Novo Nordisk, and Sanofi Aventis, this action can easily be replicated for all of their insulin products (outside of offering greater rebates to counter biosimilar competition). So far, Lilly was the only one to take this action; this was not in response to potential biosimilar competition, but in direct response to the federal and legislative call for lower-cost insulin.

Insulin Interchangeability?

When the FDA Commissioner Ned Sharpless released the final interchangeability standards for biologics, he pointed to insulins specifically: “An interchangeable insulin product may be substituted at the pharmacy, potentially leading to increased access and lower costs for patients. For chronically used biologic medications patients get at the pharmacy, such as insulin, the ability to have a licensed interchangeable that can be substituted at the pharmacy without the intervention of the prescribing health care professional—much like how generic drugs are routinely substituted for brand name drugs—could be integral to the success of reducing drug prices for patients.”

The FDA spokesperson provided BR&R the following statement: “Given our long experience regulating insulin products, and high interest among sponsors regarding the development of biosimilar and interchangeable insulin products, we’re confident that once interchangeable insulins are approved and available on the market they will bring new competition to the insulin market without compromising safety and effectiveness, and potentially result in more affordable treatment options being available to patients with diabetes.” 

Far more clinical development in biosimilar insulin must be underway to support the competition necessary for that to happen. Perhaps, the interchangeability guidelines release will spur more interest in the biosimilar insulin area. However, if clinical development is lagging in biosimilar versions of other popular forms of insulin (e.g., short- and intermediate-acting forms), then insulin price competition will be many years from becoming a reality.