The Center for Biosimilars

In the first quarter of this year, key changes occurred that indicated new commitment among federal regulators to encourage biosimilar development.

 spoke about these developments with Ha Kung Wong, JD, a patent law attorney with Venable of New York, New York. Wong has an extensive background on patent litigation, transactions, and contract negotiations in the pharmaceutical industry. He gave us his take on how these initiatives are likely to succeed.

Will manufacturers be motivated to bring products to market under the newly established biologics approval pathway under the 

Biologics Price Competition and Innovation Act

There’s an important distinction to make. Many biologics that are subject to biosimilars today are older products and their regulatory exclusivity no longer applies. But if it’s a newer product, biosimilar manufacturers are looking at a horizon 12 years away for bringing their product to market based on regulatory exclusivity, so they might have less incentive to develop a biosimilar, even if it’s the same amount of work as making a small molecule generic. That’s 1 reason why we see so many companies making generic medications. In the generic industry, pursuing multiple potential generic products may be beneficial, even if you only succeed in bringing 1 to the market. It’s potentially worthwhile from a return on investment analysis, because you have the potential for 180 days of marketing exclusivity and have automatic substitutability at the pharmacy for the reference product. On top of that, the generic small molecule process is likely less resource intensive than developing a biosimilar.

With small molecule drugs, the intellectual property (listed in the Orange Book) that surrounds the product may be less extensive than what one might see for biologics. One reason for that may be the importance of manufacturing processes to certain biologics. Because of this, among other reasons concerning the general increased complexity of biologics, there’s potential to have more intellectual property surrounding the Biologics License Application product.

Whether there is incentive to pursue a biosimilar, as compared to small molecule generics, is likely to be a highly fact-dependent analysis.

Over the past 2 years, we’ve had multiple launches of biosimilars, so we’ll get a lot more information very soon on the biosimilars market. We’ll have a much more informed view of whether this is something people would want to be involved in or not, at least from the economics perspective.

Is it possible that the newly announced FDA/Federal Trade Commission (FTC) 

to fight anticompetitive practices will improve the marketplace for biosimilars?

It’s interesting that they are affirmatively looking out for and looking to address any potential anticompetitive practices. The FDA and the FTC can significantly impact the promotion and uptake of biosimilar products, and it’s important to see that they’re proactively seeking to understand and address them with concrete steps.

What may be concerning is that many of the steps they’ve identified so far are very broad or do not significantly add to their current purview. The points that they identified in their joint statement indicated that they want to promote a coordination between these administrations in order to promote competition in the biologic market by educating consumers and providers. That’s important, and they did come out with draft guidance on promotional labeling and advertising in the biologic space, but they generally don’t do more than they normally would have done. For instance, they essentially say that you need to be truthful and nonmisleading when advertising in the biologics space. That’s true for anything that you have in advertising. Just because they explicitly identify that a rule applies to biologics products doesn’t make it more stringent. They’ve provided no additional penalties for not being truthful or misleading with biologics advertising.

One of the examples they give of misleading content is suggesting that a biosimilar is less safe or less effective because it hasn’t been licensed as interchangeable. But a company doesn’t have to be that explicit. What if a company were to simply state that no clinical studies had been conducted to demonstrate that the biosimilar can be switched with the branded product? That’s just a factual statement. Is that suggesting that the product is less safe or less effective?

What the average consumer might understand from that representation is unclear. For this to be helpful, the FDA and FTC will have to address the hard questions, and not simply address the easy questions that we already know the answers to.

It certainly may be helpful, though, that the FDA and FTC did say that companies can request an explicit review of draft promotional materials through the current process for submitting an application. That isn’t necessarily significantly different than just submitting it, because you’re going to get their comments anyway, but it may be helpful to request an explicit review of draft materials to ensure that one gets specific guidance on materials that may be concerning.

Articles

Ha Kung Wong, JD, a patent law attorney with Venable of New York, New York, discusses recent regulatory actions to promote biosimilars.

Wong Discusses Strength of Regulatory Actions

From the perspective of a practitioner, what determines biosimilar access is more complicated than price or the number of biosimilars on the market. Payment channels and institutional policies to a large degree determine the biosimilar armamentarium, according to Adam Brufsky, MD, PhD, FACP, of the University of Pittsburgh Medical Center (UPMC) in Pennsylvania.

“What happens in a large health system, especially one such as UPMC that spans the state of Pennsylvania, is that every local area has a slightly different payer mix, with a slightly different drug reimbursement schedule, and slightly different contracting with the various suppliers,” said Brufsky, who is a professor of medicine and associate division chief for the Division of Hematology and Oncology at UPMC.

A manufacturer might introduce a biosimilar on market with the statement that it will be priced at 15% less than the reference product, but when this discount is filtered through all of the other factors that influence cost, it becomes very difficult to know on a broad scale what the medical system is really paying for biosimilars, Brufsky said.

“It’s very, very complicated. It’s not as simple as just saying, “Oh, the biosimilar is 20% to 30% less than the originator,” he said.

Brufsky admits that finding this out was an eye-opener for him. “It’s a very complicated process for the pharmacy, the pharmacy and therapeutics committee, and the financial team to figure out exactly what the benefits of a biosimilar are financially. It really depends on a lot of factors that you ordinarily wouldn’t have thought of.”

This doesn’t mean that you can’t save money with biosimilars. Brufsky notes that saving money is the whole point. Biosimilars have no clinically meaningful difference from their reference biologics, according to the FDA, except that they are generally introduced to market at a discount from originator drugs. The problem is, it isn’t easy to model the difference that biosimilars are going to make to the bottom line.

“I think biosimilars are going to save us all money, but on the other hand, we just don’t know what that number is going to be at the end of the day. I think it’s going to be different depending on who you are and where you practice. I think they definitely will improve access for a lot of patients who ordinarily wouldn’t have been able to get these agents because of expense. We just have to be very careful as a medical community in understanding the exact cost savings we’re getting,” Brufsky said.

The general haziness of the financial picture is illustrated by the wide number of trastuzumab biosimilars now available on the US market. There are 5 of them, the highest number of biosimilars in the United States for any reference product, and yet owing to manufacturer decisions, wholesaler supply, formulary placement, and hospital drug selection processes, a limited number of these will be available in any particular market, thereby limiting the competitive pressure on manufacturers to lower their prices.

The real price of a biosimilar is going to depend on local availability, Brufsky notes. “There’s not going to be a one-size-fits-all concept. Payers and health systems are going to choose the biosimilars that make the best sense for them, whether it’s based on cost or reliability of supply or a review of the evidence supporting that drug.   

“The nice thing about biosimilars is that we know, from the FDA, that they are similar in activity to the reference product. You’re going to have to choose the biosimilar that works best for your particular situation. You’re going to get a cost savings, but I think it really is going to depend on the individual area,” Brufsky said.

Reference Products Sometimes Have the Edge

In some cases, however, providers will have to use the reference products. It is not possible, for example, to make a full transition to biosimilar pegfilgrastim because there are advantages to Onpro that some patients can’t do without. It’s not in the biological formulation but in the convenience of the applicator, Brufsky notes.

Some patients travel long distances and don’t have the luxury of staying in town for the follow-up injection of Udenyca, which has to be delivered in a clinic, and it’s not always possible to arrange for administration in a satellite clinic. Onpro solves that problem, he said. “There will always be people who will be on Onpro because they come from a long distance. They come from rural Pennsylvania and they don’t have anybody near them to give them the Udenyca injection the next day, and so for that reason you’re never going to get to 100%.” 

Therefore, looking for perfection on the cost side can be shortsighted, Brufsky noted. “The perfect is the enemy of the good. It should be OK to be satisfied with 80% or 85% and not drive everybody toward a 100% conversion. Hopefully, you adopt enough of the biosimilar that you can see cost savings. That’s the hope, and again, it’s a very complicated matter.”

The goal for many in the health-care system is to figure out what the biosimilar threshold is that represents the perfect balance of cost savings and convenience, he said.

Biosimilar pricing is not as simple as a manufacturer's stated discount to the reference product cost, according to Adam Brufsky, MD, PhD, FACP, of the University of Pittsburgh Medical Center (UPMC) in Pennsylvania.

UPMC Expert Discusses Price Variation for Biosimilars

Clinical pharmacists can play an important role in educating consumers about biosimilars, but they need to familiarize themselves with these products, said an expert panel recently.

“Clinical pharmacists are in a unique position to provide appropriate patient and provider education. There’s also an increased impact by pharmacists in managing the formularies with multiple biosimilars available,” Antony Mato, MD, MSCE, said.

To do this, they need to know the difference between different biologics, which represent the fastest growing therapeutic class of drugs. In 2017, an estimated $120.1 billion was spent on biological medicines, up from $76.9 billion in 2013, according to a 

The panel said clinical pharmacists may be more familiar with small molecule drugs.

by the International Society of Oncology Pharmacy Practitioners revealed that pharmacists feel they lack knowledge when it comes to comparing the efficacy of biosimilars with originator products (74.4%), switching patients to biosimilars from originator products (74.4%), and understanding the safety of biosimilars (73.3%).

Limited financial support, heavy workloads, and poor educational resources were identified as challenges to expanding their knowledge of biosimilars.

“For small-molecule drugs, the brand originator versus the generic, it’s very easy to re-create these identical copies with a chemical synthesis. We have these raw materials that we know the chemical formula for, so we can make these copies,” Tim Peterson, PharmD, BCOP, said, in the panel discussion.

Biologics are developed from recombinant DNA using a vector inserted into a host cell. They can be very large molecules with high molecular weights. This means that there are differences in amino acid sequences, protein aggregation and folding, and variability between manufacturers in processing.

For the full story on the panel discussion, visit 

A panel of experts discusses the rising class of biological agents and why clinical pharmacists need to deepen their knowledge.
 

Biosimilar Knowledge is Essential to Modern Pharmacy

Minnesota Governor Tim Walz, on Thursday, signed into law 

, a drug whose high prices are blamed on the difficulty of market entry for rival producers.

The new law requires manufacturers to make at least a 30-day supply of insulin available for those who are in extreme need and have a prescription but cannot afford the drug. Dispensing pharmacies will be to collect a $35 copayment for this 30-day supply from patients with diabetes. Confirmed Minnesota residents may receive up to a 90-day supply. The law provides for hefty fines on manufacturers who do not comply.

State actions to improve access to insulin have come as a newly enacted, abbreviated FDA approval pathway for insulin biosimilars has yet to bear fruit.

The Minnesota action is the latest in a series of moves to address the large number of patients believed to have difficulty coming up with the money needed for diabetes treatment. In March, Medicare 

 a test program that would limit the monthly copay for most insulins to $35.

Colorado, Virginia, Maine, and New Mexico have established copay caps ranging from $100 to $25. Other states have enacted similar measures.

PhRMA, a trade group representing pharmaceutical manufacturers, has advocated that rebates and discounts offered within the drug supply chain be reallocated to address insulin affordability issues.

“We also need to advance policy solutions that delink supply chain payments from the list price of a medicine, provide first dollar coverage of insulin for high-deductible health plan patients, count third-party discount programs toward deductibles, and provide flat copays for insulin for patients receiving cost-sharing subsidies in the exchanges,” 

A bill designed to provide assistance to patients who cannot afford their insulin was signed into law by Minnesota Governor Tim Walz.

Minnesota Governor Signs Emergency Insulin Bill

Oncology pharmacy practitioners have a craving to know more about key aspects of biosimilars, 

 conducted by the International Society of Oncology Pharmacy Practitioners (ISOPP).

Pharmacy practitioners said they feel particularly knowledge-deficient in the following areas:

Evaluating comparative efficacy of a biosimilar to an originator product (74.4%)

Managing the switchover to a biosimilar from the original product (74.4%)

Understanding medication safety issues in relation to biosimilars use (73.3%)

They said the most common challenges they face in obtaining education on biosimilars include limited financial support (38.4%), heavy workload (31.4%), and inadequate educational resources (27.9%).

ISOPP described the survey as one of the most comprehensive yet on oncology pharmacy provider knowledge needs for use of biosimilars, with 72% having more than 10 years of experience in the oncology pharmacy field. Most of the respondents practiced oncology pharmacy in Europe (27.9%), North America (17.4%), and Asia (16.3%). 

According to the study, 74% of respondents’ institutions used biosimilar products. Of the remainder, 46% said they were undecided about using biosimilars, and 31.8% said biosimilars were unavailable in their country.

Just 27 respondents (46.4%) reported that usage was guided by national policies or guidelines, while the majority stated that biosimilar use was guided by institutional policies (64%) or by the local healthcare team (46.4%).

Respondents whose institutions were in high- and high-middle income countries used biosimilars according to guidance from the FDA (United States), the  National Health Service (England), or the European Medicine Agency. In some cases, pharmacy and therapeutics committees made decisions on the use of biosimilars.

In low-middle income and low-income countries, decisions to switch to a biosimilar were generally made independently by a treating oncologist, and there was no standard policy or decision-making process, survey respondents said.

Fifty percent of respondents reported frequent or very frequent use of biosmilars for cancer treatment, and 45.4% rated themselves above average to excellent in their understanding of regulatory approval processes for these agents.

Influencing the Clinician’s Choice of Agents

Just 13% reported they were often or very often able to influence a clinician’s choice on whether to employ a biosimilar, and 35% indicated they were sometimes able to influence a clinician’s choice. “Institutional and regional policies and guidelines, education, and word-of-mouth were frequently utilized by respondents to influence prescribers,” the authors wrote.

According to the survey, 56% of respondents rated themselves good to excellent in their knowledge of preparation and administration of biosimilar products. They said they rely heavily on package inserts, other product information, and 

With regard to other areas of knowledge in need of improvement, respondents identified biosimilar indications, budgetary implications, administration guidelines, and patient education.

ISOPP said it would incorporate the findings into future efforts to educate oncology pharmacy practitioners.

“There is room to improve oncology pharmacists’ understanding of biosimilar products, including the regulatory approval process and the practical aspects of implementation as well as the administration of these products,” study authors concluded.

A percentage of oncology pharmacy practitioners report their guidance on biosimilars is influential with clinicians, but many feel their knowledge of biosimilars is deficient in a number of important areas.
 

Oncology Pharmacists Need More Biosimilar Knowledge

Although the FDA is hoping a new biologics approval pathway will lead to insulin biosimilars, higher production, and lower prices, and thereby alleviate a crisis of insufficient supply, Minnesota is taking matters into its own hands.

An emergency bill that would create a statewide insulin assistance program for Minnesotans is on the way to the Minnesota Senate and is expected to pass before going to Governor Tim Walz’s desk for his signature.

The Alec Smith Insulin Affordability Act is named after a man who aged off his mother’s policy and died in 2017 at age 26 because he could no longer afford the $1300 per month he needed for insulin and supplies. It 

 Tuesday in the Minnesota House 111-22. The bill’s proponents have noted other Minnesotans who have died from insulin rationing.

 a new regulatory pathway under which it anticipates competitor biosimilars for established insulin products will emerge. A 10-year transition built into the Biologics Price Competition and Innovation Act of 2009 allows for the biologics pathway approval of insulins and other drugs previously classified as small-molecule drugs and regulated under the Food, Drug, and Cosmetic Act.

“Thanks to the advocacy of thousands of Minnesotans, and to Representative Michael Howard’s dedicated leadership, this legislation is on its way to the Governor’s desk,” said House Speaker Melissa Hortman.

For those who cannot afford their insulin and are facing an emergency need, the bill would provide those with diabetes access to an emergency 30-day supply at their pharmacy for a co-payment of $35. The bill would grant eligibility to the uninsured, underinsured, Medicare beneficiaries, and those whose co-pays are not low enough.

Patients with diabetes would also be connected with options for long-term, affordable insulin coverage.

, manufacturers would be liable substantial fines for failure to comply.

“Lives are on the line—we can't let 1 more person lose their life because they can't afford the medication that keeps them alive,” said House Majority Leader Ryan 

, who blamed greed for the current prices of insulin, which have tripled in Minnesota in the past 10 years.

The bill was supported by patients, doctors, nurses, and pharmacists, including the AARP, Minnesota Nurses Association, Minnesota Medical Association, and Minnesota Pharmacists Association.

The bill will be funded largely by a fee on insulin manufacturers.

After noting the stories of individuals with diabetes dying due to their inability to afford insulin, the Minnesota House has passed an emergency insulin bill that is expected to move rapidly through the Senate to the governor’s desk.

Minnesota Bill for Insulin Access Moves Forward

Mylan and Biocon have announced the launch of their pegfilgrastim biosimilar (Fulphila) in Australia.

The product, a biosimilar to Amgen’s Neulasta, was launched in the United States in 2018.

Fulphila, for the treatment of patients with cancer following chemotherapy, was approved by Australia’s Therapeutic Goods Administration. The agent helps to shorten the duration of severe neutropenia and reduce the incidence of infections, as manifested by febrile neutropenia.

Fulphilia is the third biosimilar to be commercialized in Australia by the partnership between Mylan and Biocon, according to Sylvain Vigneault, the Australia country manager for Mylan.

“Biosimilars ensure patients have timely and affordable access to quality, safe, and effective treatments in a way that is sustainable,” he 

The Australian government has endeavored to get biosimilars into circulation through the Biosimilar Awareness Initiative, established in 2015, and in 2018 the country established a $5 million grant through the Generic and Biosimilar Medicines Association to improve education on biosimilars and activities that promote appropriate prescribing, dispensing, and use of biosimilar medications.

 26 biosimilars since 2010, including 3 other pegfilgrastim biosimilars and 5 trastuzumab products besides the reference Herceptin. Fifteen of those biosimilars are subsidized by the country’s Pharmaceutical Benefits Scheme.

Mylan has a portfolio of 20 biosimilar and insulin analog products in development or on the market.

Fulphilia was codeveloped by Biocon and Mylan and was the first biosimilar pegfilgrastim to be approved in the United States. The biosimilar has received regulatory approval in more than 30 countries, according to Biocon.

Biocon has a pipeline of 28 molecules, including 11 with Mylan and a number with Sandoz, and is also developing agents independently. The company has a therapeutic armamentarium that includes agents for diabetes, cancer, immunology, dermatology, ophthalmology, neurology, rheumatology, and inflammatory diseases.

 their trastuzumab biosimilar (Ogivri) on the Australian market. It became the first trastuzumab biosimilar to appear in the Australian marketplace.

Also last year, Biocon and Mylan launched their biosimilar insulin glargine, Semglee, in Australia.

With the launch of Mylan and Biocon’s pegfilgrastim biosimilar, Australia adds another biosimilar to its portfolio of biosimilars in circulation.

Mylan and Biocon Launch Pegfilgrastim Biosimilar in Australia

Well before biosimilar anticancer agents became available, oncologists gained familiarity using biosimilars as supportive care products. These included growth factor receptor inhibitors, which impede cell growth.

“We were very used to already incorporating biosimilars into the treatment management of patients with breast cancer,” said Lee S. Schwartzberg, MD, FACP, in an overview of the transition to therapeutic biosimilars in oncology. “Some physicians have taken a different approach to a supportive care medication as opposed to a therapeutic medication, where the outcome is truly potentially lifesaving.”

Schwartzberg is chief medical director of West Cancer Center and chief of the Division of Hematology/Oncology at the University of Tennessee Health Science Center, both in Memphis.

In breast cancer, trastuzumab biosimilars are now used to treat HER2-positive disease. Schwartzberg described trastuzumab as a “revolutionary molecule in terms of a biologic that helped people live longer in the metastatic setting and actually cured more people in the early stage setting.”

Five trastuzumab biosimilars have been approved by the FDA, and 4 of them are on the market.

“We started using the first one that was available on the market, although not the first one that was approved by the FDA,” he said. That product was Kanjinti, which was launched July of 2019.

The assigned biosimilar name and suffix for this agent are trastuzumab-anna. “That’s important because at the pharmacy level you want to make sure you’re administering the right drug. So, trastuzumab as an originator has its name [Herceptin],” Schwartzberg said.

 “Whatever drug we’ve decided to use, we keep using that same one. And so, there shouldn’t be any confusion. We don’t just say biosimilar trastuzumab; it’s the actual name that we use. And, of course, we use generic names at the pharmacy level,” he said.

When the FDA approves a biosimilar, it is certifying that the agent has no clinically meaningful differences to the originator drug. That goes for all the trastuzumab biosimilars that have been approved.

“I am comfortable, personally, with using any of the biosimilars that are available that the FDA has approved, because I believe in the process of approval,” Schwartzberg said. “I believe that all of the boxes have been checked. And I can feel comfortable that if I use a biosimilar trastuzumab, it will work the same way as the originator trastuzumab does.”

“Kanjinti, the biosimilar that I am using, like all the others, has been tested in a clinical trial. This particular agent was used with neoadjuvant chemotherapy in HER2-positive breast cancer. And the primary end point of that trial was pathologic complete response rate, which is a well-known surrogate end point that we use for determining long-term benefit for drugs in the neoadjuvant space for HER2-positive cancer,” he said.

“In addition, Kanjinti was used in the adjuvant setting. So, there was actually another comparison between trastuzumab and Kanjinti in the adjuvant setting to complete the year of trastuzumab therapy that is standard for all patients with HER2-positive disease.”

The clinical data on this biosimilar and the 4 other trastuzumab biosimilars are good and demonstrate that safety is equivalent to the originator agent, he said. “In a clinical trial setting, the drug worked within that narrow range that the standard drug would work.”

This gives clinicians confidence that they can use the biosimilar instead of the originator product for HER2-positive breast cancer, Schwartzberg said.

The introduction of biosimilars as anticancer therapies was preceded by a period of supportive care biosimilars. Lee S. Schwartzberg, MD, FACP, describes how he and other clinicians decide which of these agents to use.

Choosing the Right Biosimilar for Cancer Care

When choosing a biosimilar for a patient, a lot goes into the equation, said Lee S. Schwartzberg, MD, FACP, chief medical director of West Cancer Center and chief of the Division of Hematology/Oncology at the University of Tennessee Health Science Center, both in Memphis.

The strength of the regulatory process behind the biosimilar counts, as does the quality and breadth of clinical trial data, as well as the reliability of the supply chain and patient consent. But it’s also important to understand how data can be extrapolated to support the use of a biosimilar in diverse settings, Schwartzberg said.  

He discussed all of these issues in an overview of how biosimilars are incorporated into his Memphis practice. Overall, these agents have been a successful experience for providers and patients, but some thought and a little discrimination needs to go into their selection, he said.

“The regulatory definition from the FDA is that you do 1 clinical trial in a sensitive population, so you can pick up any difference whatsoever between the originator and the biosimilar. And if you get a result that shows equivalence, then you can extrapolate that into other settings in the same disease. But also, you can extrapolate that into any other approved indication for a particular drug,” he said.

An example is trastuzumab, which is approved in gastric cancer and gastroesophageal junction cancers that are 

“The label for the trastuzumab biosimilars allows it to be used in those settings, even though it, to my knowledge, it has not been tested extensively in gastric cancer. Most of the studies have been in 

-positive metastatic or early stage breast cancer, because that’s the overwhelming group that has this HER2 alteration.”

This extrapolation concept is important also within breast cancer, Schwartzberg said. “If you’re using a biosimilar that was tested in the neoadjuvant and adjuvant setting, it can also be used in the metastatic setting. So, if we have a patient with metastatic 

-positive breast cancer for whom trastuzumab is indicated, which is virtually all of them, I feel comfortable also extrapolating and using it in that setting as well.”

Schwartzberg believes that any biosimilar can be extrapolated to any other indication in the FDA label for a reference product. “Because there are a lack of data in areas where there’s not an approval and where there weren’t previous studies, I would be hesitant to take a biosimilar, just like I would be with the originator, and use it in a nonindication situation, or at least where there have not been studies to date.”

Biosimilars are a valuable addition to the armamentarium, but their chief advantage is that they cost less than originator products, he said. Development of these products is made easier by the simplified regulatory pathway that applies to biosimilars. Clinical development, the most expensive part of drug development, is less heavily emphasized among requirements for biosimilar approval.

“It’s more about showing that the molecule is like the originator molecule. You don’t have to spend tens of millions, or hundreds of millions of dollars to test [the biosimilar candidate] in every population in a large group of patients,” Schwartzberg said.

Biosimilars reduce costs for patients and the healthcare system because they are typically priced at a substantial discount to the originator drug.

“In our United States healthcare system, we need cost reduction maneuvers [such as biosimilar development], because the cost of cancer care, the cost of healthcare in general, is out of sight and out of control. So, anything we can do to reduce the cost without reducing the value or the effectiveness of a drug is a real benefit for everyone in the system.”

One thing that does require careful consideration on the part of physicians is the origin of the biosimilar, in terms of manufacturing, Schwartzberg said. Biosimilars are complex biologics that have to be manufactured under very tightly controlled conditions, with quality assurance.

“You can’t just set up a plant and do this,” he said. “This is in living cells. Plus, because they’re so complex they actually can vary over time by a factory that’s doing it maybe a little differently than another. Over time it changes. So, it requires a lot of attention. Therefore, you should always think about the company that’s making it, their experience in making biologicals in the past, and the supply.”

Schwartzberg noted how distressing drug supply problems can be and why it’s important to consider stability of the supply chain when choosing a biosimilar for a patient. “The last thing you want is to be prescribing a drug to a patient that’s working and then call the manufacturer for another supply, and they say, ‘The factory went down and we’re not going to have it next month.’ That’s a terrible thing for a patient. So, reliability, experience in manufacturing biologicals, and making sure the supply chain is good, as well as the price, which is very important, are all factors to consider when choosing a biosimilar.”

Schwartzberg said his clinical experience with biosimilars has been very favorable. “I’m confident in the companies that are bringing biosimilars to market. We make sure that they are reputable companies with lots of experience and that we’re not going to have any disruption in the supply chain. We make sure that the pricing is fair, and that there’s value to every member, every [stakeholder]. And our patients have been very comfortable accepting biosimilars.”

In his practice, he explained, patient consent is paramount for decisions to use a biosimilar. The consent form includes a review of potential adverse effects so the patient is aware of them. “Biologicals, and biologicals like trastuzumab, which is an antibody, occasionally cause infusion reactions or other reactions. Like every other drug, and certainly every other biological, there is a potential for toxicity and adverse effects, as well as the specific adverse effects.”

When it comes to switching from a reference biologic to a biosimilar, the practice will have the provider talk to the patient and explain why the biosimilar is being proposed. Patients are told, “We have another version of the drug you’re getting. It works just as well as the other one. It’s a biosimilar, and it’s highly similar in terms of its efficacy and its safety, but it will cost you less, it will cost us less, and we’d like to change you to that. Are you comfortable with that?” Most of the time, patients are comfortable with the switch, and they know they are on a new drug, and the informed consent means everybody is protected, Schwartzberg said.

Oncologist/hematologist Lee S. Schwartzberg, MD, FACP, describes some important considerations for using biosimilars in clinical practice.

Schwartzberg Explains Biosimilar Use in Clinical Practice

NeuClone Pharmaceuticals announced successful completion of monitoring visits and blood sampling for patients in the phase 1 clinical trial for its ustekinumab biosimilar candidate for treatment of plaque psoriasis, psoriatic arthritis, Crohn disease, and ulcerative colitis. Ustekinumab is an antibody that targets interleukin-12 and interleukin-23.

 biosimilar candidate is NeuLara and it references Stelara, a Janssen Pharmaceutical Companies product that reached global sales of $6.6 billion in 2019 and is anticipated to achieve sales of $7.8 billion in 2024, according to 

 is one of several biosimilars developed by NeuClone in partnership with Serum Institute of India.

Over 200 healthy volunteers received a single dose of either NeuLara, US-sourced Stelara, or EU-sourced Stelara, after which they were monitored for up to 105 days. Samples were collected for pharmacokinetic and antidrug antibody similarity testing.

NeuClone said an interim analysis indicates the safety and tolerability profiles were comparable between the 3 blinded treatment arms. The final clinical study report is anticipated in the third quarter of 2020.

"We are delighted with the progress of NeuLara through its phase 1 clinical trial," stated Noelle Sunstrom, chief executive officer and founder of NeuClone, which is based in Sydney, Australia. "Our attention now shifts to the final stages of development required for approval and supply of NeuLara to patients globally."

In December, Neuclone announced that its proposed biosimilar trastuzumab, referencing Herceptin, had 

 all primary and secondary end points in a phase 1 clinical study that compared the product with its US and EU reference products. The product, also being developed in partnership with Serum Institute of India, will prospectively be sold under the name NeuCeptin if it gains regulatory approval.

NeuClone said phase 1 patient monitoring and blood sampling has been completed for its ustekinumab biosimilar candidate, which is targeted at the $6.6 billion in annual revenue earned by Stelara, a Janssen Pharmaceutical Companies product.
 