Tony Hagen is senior managing editor for The Center for Biosimilars

Tony Hagen

Oral technology for biologics seems poised to gather steam rapidly once it is demonstrated that pill formulations can succeed in patient therapy. A few recent surveys suggest that physicians in the field of rheumatology would lean toward use of pills over injections as a way to improve very high patient nonadherence rates.

According to a 2018 study, there are 10.2 million adults 50 years and older who have osteoporosis and another 43.4 million with low bone mass. Authors of the study said as many as half of patients recommended for osteoporosis therapy do not take their medication. Data were drawn from the 

study of 7749 patients 50 years or older.

Many reasons for nonadherence were cited; however, use of syringes was not specifically noted as a top reason. Fear of adverse events or contraindications was reported most often by patients in the study (53.3%), followed by not liking to take medicines (25.3%) and doubts that the medicine would improve health (16.7%).

Despite these results, surveys have suggested that oral biologic formulations would be rapidly accepted by physicians if they become available. In 2018, Rani Therapeutics, in partnership with polling group Frost & Sullivan, touted results of a 

they said indicated pill formulations would help biosimilar companies achieve market share gains against makers of original biologics.

The survey comprised 500 patients and more than 100 physicians, including gastroenterologists and rheumatologists, and indicated 88% of patients and 86% of rheumatologists and gastroenterologists would switch from adalimumab injections to once-daily adalimumab pills should those become available.

The Humira originator version of adalimumab is not yet available in pill form; however, its maker, AbbVie, has since introduced the oral follow-on product Rinvoq (upadacitinib), a Janus kinase (JAK) inhibitor also for the treatment of rheumatoid arthritis. JAK inhibitors help to suppress cell signaling that leads to inflammation characteristic of rheumatic conditions.

 in the third quarter of 2019 and garnered $47 million in sales for that entire year, so the jury remains out whether this product can carry consumer demand away from Humira, which will lose exclusivity in the United States in 2023, at which time multiple biosimilar versions are expected to hit the market. Humira’s 2019 US sales were $14.9 billion.

The Frost & Sullivan survey found high estimates of adalimumab nonadherence. Sixty-two percent of patients reported they skip their injections or consistently fail to inject the drug as prescribed. Survey results also indicated 70% of rheumatologists and 92% of gastroenterologists anticipate that adherence would significantly improve via transitions from injection to pill delivery.

"What is clear from our research is that patients and physicians are overwhelmingly in favor of replacing a syringe with a pill,” said Charlie Whelan, director of consulting for Frost & Sullivan’s Healthcare & Life Sciences practice.

In July 2020, Entera Bio reported results of 2 market 

of clinicians who treat patients with osteoporosis, one conducted among physicians in the United States, Canada, and Europe, and the other done in Japan. Entera Bio said the clinicians were overwhelmingly anticipating that an oral formulation of parathyroid hormone (PTH) for the treatment of moderate to severe osteoporosis would improve adherence and ease of administration.

“Due to the high cost, inconvenience, and pain associated with injectable osteoanabolic products, which are currently the standard of care for treating moderate to severe osteoporosis, it is estimated that only 5% of patients with severe osteoporosis actually receive treatment for their disease,” Entera CEO Adam Gridley said in a statement. “Remarkably, approximately 45% of the participating physicians indicated the oral PTH would be their first line treatment choice for their patients with severe osteoporosis.”

The survey in the United States, Canada, and Europe comprised mostly rheumatologists and endocrinologists, and 84% said they would be likely to prescribe oral PTH for osteoporosis; the equivalent percentage for Japanese survey participants, who comprised mostly orthopedists, was 89%.

Entera Bio has 2 product candidates in phase 2 clinical development: EB613 for the treatment of osteoporosis and EB612 for the treatment of hypoparathyroidism. The company is developing a carrier-molecule oral vehicle for biologics that binds the therapy to receptor-specific molecules that can penetrate the intestinal lining, providing passage and therapy delivery to the targeted area of the body.

“We believe the promising feedback from physicians currently involved in the care of high fracture risk patients with current osteoporosis medications may result in a rapid market adoption of the first oral PTH product,” Arthur Santora, chief medical officer of Entera Bio, said.

Articles

Product differentiation via oral formulations of biologics could be the next battleground between originators and biosimilar companies.

Surveys Suggest Oral Biosimilars Could Dominate

The holy grail of an oral biologic has inspired many pharmaceutical companies to enter the race. Among biosimilar makers, the most recent of these was Celltrion, which partnered with Intract Pharma to incorporate its pill technology into an infliximab treatment that would avoid the need for injections.

There are various companies like Intract that have worked to circumvent the powerful digestive and body protection systems in the digestive system so that medicine can be delivered through the lower intestine, where if successful, the therapeutic effect may be more direct and more effective.

The Incheon, Republic of Korea–based Celltrion contends that its oral formulation of infliximab would be the first of its kind. But before that, Celltrion and Intract, a United Kingdom–based company, have to prove that the technology works.

Intract’s pill technology uses a shell covered with a coating that resists breakdown as it passes through the large and small intestines, only releasing the medication in the colon. The company is licensing the product to interested parties. Within the spectrum of inflammatory bowel disease (IBD), Intract is moving forward with oral infliximab formulations that would treat ulcerative colitis and Crohn disease.

Intract anticipates a phase 1b trial in ulcerative colitis to initiate in the second half of 2021 and a phase 2 trial for the Crohn disease pill formulation in the first half of 2022. Whereas injectible versions of infliximab need to be refrigerated, Intract Pharma says its oral version would be stable and storable at room temperature, making it possible for patients to self-administer from their homes.

“We anticipate that the oral infliximab product, which we will co-develop with Celltrion Group, will have an improved safety profile and will offer a less expensive biotherapeutic treatment for IBD

 "We are hopeful that the product will address a large proportion of the IBD market, potentially replacing steroid and immune-suppressive drugs in addition to capturing a large share of the biologics market."

Multiple technologies are under development for the oral delivery of biologics. A review by the Pharmaceutical Journal in January described the formidable obstacles to this achievement. As large and complex molecules, biologics are “extremely sensitive to the physical and chemical conditions of the gastrointestinal environment,” which is why they have been restricted to delivery via injection so far, the article explained.

However, the growing market for biologics and the perceived value of oral biologics have given impetus to the development of oral formulations. In the case of insulin, delivery through the digestive system would most closely resemble the natural provision of insulin secreted via the pancreas. It would also obviate the need for needles and bring down the overall costs of care.

Various methods for making oral biologics work include pills are embedded with medicine-containing microneedles that become exposed as the pills are digested. These embed themselves in the lining of the intestine and enable the drug to penetrate the mucosal and epithelial walls. Alternative methods under study include attaching the biotherapeutic to a molecule enabled with a receptor that grants it passage through the intestinal epithelium. These transport-enabling molecules include peptides and proteins.

Rani Therapeutics, based in San Jose, California, has a micro-needle approach that it has touted as a way for biosimilar companies to diversify their products from originator biologics and achieve market share gains. In January 2020 the company announced positive 

 from a phase 1 study of an oral version of octreotide, a biologic used for the treatment of acromegaly and neuroendocrine tumors. The technology was evaluated in a group of 58 healthy volunteers and Rani Therapeutics reported that bioavailability of octreotide was greater than 70%.

Entera Bio is an example of a company that is developing a conjugate molecule–based technology. The company’s oral delivery vehicle works via use of a carrier molecule or “synthetic absorption enhancer,” to enable the walls of the intestine to absorb biologic drugs, along with protease inhibitors that resist the enzymatic degradation process within the digestive system. “Oral drug delivery provides significantly more flexibility, both in size of dose and number of doses per day, than injectable drugs, which are frequently administered by preset injection pen and only once per day,” the company 

In 2018, Amgen and Entera Bio began a collaboration to develop orally administered versions of biologic drugs. In June Entera Bio reported positive interim results from an ongoing phase 2 clinical trial of an oral parathyroid hormone (EB613) for the treatment of osteoporosis. The company 

 a 1.44% increase in bone mineral density in the lumbar spine in the 1.5 mg treatment arm versus a mean decrease of 0.71% in the placebo arm. Entera Bio added that results suggested higher dosages will increase efficacy.

The partnership with Amgen involves the development of an undisclosed, early stage biologic for the treatment of inflammatory disease, among other illnesses. “This collaboration is an important validation of our platform technology. Importantly, the first program included in this agreement is very different from the [oral parathyroid hormone] in Entera’s pipeline, highlighting the broad applicability of our technology,” the company 

Oral biologics would offer many advantages over injectable drugs, and some companies believe they are on the cusp of making this happen.

Chasing the Holy Grail of Oral Biologics

An analytical similarity assessment has demonstrated that the Amgen and Allergan rituximab biosimilar candidate (ABP 798) is structurally and functionally similar to its reference biologic counterparts marketed in the United States and Europe.

Amgen, of Thousand Oaks, California, and Allergan, based in Dublin, Ireland, 

a biologics license application to the FDA for review of ABP 798 in December 2019. ABP is a CD20-directed antibody that promotes cancer cell death through cytolysis, or excess fluid absorption. The reference product is indicated for treatment of non-Hodgkin lymphoma, chronic lymphocytic leukemia, granulomatosis with polyangiitis, and microscopic polyangiitis.

The analytical assessment evaluated the antigen binding properties of ABP 798 and demonstrated that ABP 798 has similar amino acid sequence; structure; glycan profile, which relates to pharmacodynamic and pharmacokinetic attributes; and biological activity. There were minor differences in biochemical attributes that were not considered clinically meaningful.

The authors of the study concluded that ABP 798 is “highly analytically similar” to the reference rituximab product (Rituxan [United States], MabThera [European Union]) and said the findings support use of ABP 798 in all approved indications of the reference product.

ABP 798 was developed to offer the same strength and dosage approved for reference rituximab in the United States and Europe: 10 mg/mL in 100-mg and 50-mg single-use vials for intravenous administration. The study evaluated active and inactive ingredients to assess safety, efficacy, and product quality of the biosimilar candidate.

Amgen developed the biosimilar and is collaborating with Allergan to develop and commercialize 4 oncology antibody biosimilars, including ABP 798. Allergan became a property of AbbVie in May 2020.

There are 2 rituximab biosimilars on the market in the United States currently: Ruxience (Pfizer) and Truxima (Celltrion/Teva).





Seo N, Huang Z, Kuhns S. Analytical and functional similarity of biosimilar ABP 798 with rituximab reference product. 

. Published online September 1, 2020. doi:10.1016/j.biologicals.2020.08.002


Results of an analytical similarity test provide additional evidence in support of a biologics license application filed with the FDA by Amgen and Allergan.

Amgen-Allergan Rituximab Candidate Meets Test for Biosimilarity

The nocebo effect is real and documented, and in inflammatory bowel disease (IBD) it’s important to plan interventions early in the treatment cycle to head off psychological rejection of biosimilars, according to authors of an 

“The nocebo effect is defined as a negative effect of a pharmacological or nonpharmacological medical treatment that is induced by patients’ expectations and that is unrelated to the physiological action of the treatment,” the authors wrote.

Patients with ulcerative colitis and Crohn disease are vulnerable to depression (40.1%) and anxiety disorders (30.6%) and are highly sensitive to perceived consequences of switching to biosimilars which, although equal in safety and efficacy to originator products, may not inspire the same confidence that patients derive from established brands, they wrote.

They said physicians and other health care professionals can play a significant role in developing trust and a sense of security in patients for the use of biosimilars, and this in turn can reduce biosimilar rejection and improve outcomes, and thereby contribute to the value proposition that lower cost biosimilars have to offer. They also recommended that mental health professionals be included in IBD management teams.

In the age of widely disseminated health information via the internet and social media, where patients can obtain incorrect information or be strongly influenced by opinions coming from non—health professional sources, how these influences may contribute to the nocebo effect cannot be ignored, they said.

“The nocebo effect might prevent the widespread uptake of biosimilars, ultimately undermining the positive cost-saving effects,” the authors wrote. In their review they summarized much recent evidence on the nocebo effect with an eye toward providing up-to-date guidance for health care professionals.

Many things can contribute to the development of the nocebo effect. The authors noted that patients who have experienced adverse events with an originator therapy will be more likely to experience the nocebo effect, and so an upfront explanation by a physician who is familiar with biosimilars and can explain their value and safety and efficacy can make a huge difference in whether patients accept and adhere to biosimilar treatment, the authors said.

“Awareness of nocebo phenomenon is of paramount importance, since IBD patients commonly report fear of drug-related side effects, and high nocebo percentages are expected in chronic conditions characterized by recurrence of symptoms, such as ulcerative colitis and Crohn disease,” they wrote.

Among many examples they cited, the authors noted a European study of patients with IBD (n = 1181) whose findings indicated 38.6% of patients were worried about the safety profile of biosimilars. A 1-year pragmatic study to assess the incidence of nocebo effect in patients who switched from infliximab originator to an infliximab biosimilar found no significant statistical change in disease activity or biomarkers for those treated with originator vs biosimilar infliximab, but demonstrated an overall nocebo rate of 12.9% in patients with IBD. Nocebo in this study was defined as an unexplained, unfavorable therapeutic response following a switch to a biosimilar, followed by a beneficial effect after the innovator drug was resumed.

In another study, patients with IBD were given an interview with a gastroenterologist during which information on biosimilars’ efficacy and safety were explained to patients, and follow-up information was provided, and it was observed via survey that the interview “changed the opinion on biosimilars in about two-thirds of respondents (64.7%) and in 60% of cases influenced the decision to switch” to biosimilars.”

The authors concluded, “Obviously, a detailed physician’s knowledge of efficacy and safety of biosimilars and nocebo effect is an indispensable requirement for an effective communication.”

Further, they recommended efforts be made to identify patients most at risk for the nocebo effect, which they suggested could be achieved via the use of tools such as The Perceived Sensitivity to Medicines score, a 5-item checklist that investigates perceived sensitivity or “super-reaction” to medicines and previous drug reactions.

D’Amico F, Solitano V, Peyrin-Biroulet L, Danese S. Nocebo effect and biosimilars in inflammatory bowel diseases: what’s new and what’s next? 

. Published online August 28, 2020. doi:10.1080/14712598.2020.1817374

Multiple studies indicate the nocebo effect is particularly influential in the treatment of inflammatory bowel disease (IBD), according to an opinion piece.

Opinion: Incorporate Nocebo Planning Into IBD Treatment Strategy

As Samsung Bioepis moves ahead with the launch of its recently approved bevacizumab biosimilar Aybintio in Europe, it will have to contend with diverse individual market challenges within the European community. For starters, however, there are a few markets where the on-ramp gradient is relatively smooth: Germany, the United Kingdom, and the Nordic countries (eg, Denmark, Sweden, Norway), said Jonathan Sweeting, head of Europe for Samsung Bioepis, in an interview with The Center for Biosimilars

In those countries, “You can launch pretty much immediately with minimal additional effort, certainly from a pricing and reimbursement perspective. Spain and France tend to have a slightly more formal pricing and reimbursement review that can take a few months,” he said.

 of Aybintio, coronavirus disease 2019 (COVID-19) and its effects on regulatory and marketing activities, and Samsung Bioepis’ outlook on European markets for biosimilars.

In partnership with Biogen and Merck, the Incheon, Republic of Korea—based company already is well experienced with the European market. They have a strongly performing portfolio of biosimilars that includes an etanercept (Benepali), which competes “head to head in terms of market share” with the originator product Enbrel; an infliximab (Flixabi), which has achieved leading market positions in some European countries; a trastuzumab (Ontruzant), which now leads the trastuzumab biosimilar pack for market share in Europe; and an adalimumab (Imraldi), which competes successfully in a crowded market of multiple other adalimumab biosimilars, Sweeting said. “We hold the number 2 position from a biosimilar perspective, and we continue to see great growth potential.”

Outsiders often consider Europe as a kind of “collective” when it comes to bringing products to market, but that’s far from the truth, Sweeting said. Each country is its own market and within that market there are further divisions, he said. Country-by-country policies, regulations, and strength of competition each play a role in how successful a product launch is going to be.

Tenders, or bidding processes for drug acceptance on formulary, may be tied to regions within a country or tied to divisions within a health care system, Sweeting noted.

Some supply contracts within European countries may involve negotiated agreements with multiple manufacturers. “In some cases, if you’re a later entrant onto the market, you can approach a buying group that may have already entered into a contract and make a counter proposal, and they may or may not consider it.”

“The reality is…on a day to day basis, we’re constantly having to adjust and operate in a way that’s in keeping with the specific market that we’re talking about,” Sweeting said.

Aybintio is not the first bevacizumab biosimilar to arrive in Europe; however, “We consider ourselves to be in the first wave,” Sweeting said. “In general, we see a good opportunity to compete with that first wave.”

Samsung Bioepis is not disclosing the discount from reference product it intends to offer for Aybintio in Europe. But Sweeting said originator pricing for a 400 mg vial of bevacizumab currently stands around $850 and biosimilar discounts in Europe can be sizeable.

The various policies in Europe for setting product reimbursement combined with heavy competition have been viewed as pulling support out from underneath prices. This is a fact of life in biosimilar markets as it is for other products, Sweeting notes.

“Of course, you‘ll find that various pricing and reimbursement authorities and health care systems across Europe…will mandate certain price reductions at different points in time in a fairly structured way,” he said. “The contracting or tender-based markets that we’re competing in of course are mainly driven by natural competitive forces, and some companies choose to compete in certain tenders and not in others, with a view to maintaining slightly higher prices. Other companies will compete everywhere and perhaps slightly differentiate their pricing approach dependent upon the size of the tender or the contract that they’re working on.

“You do also find the prices come down more quickly in some therapeutic areas and through some channels, often in the hospital-based channels—we tend to find [this happens] more so than they might do in the retail channel. Ultimately, this comes down to how many products are on the market, how quickly they get there, and ultimately, the internal decision making within the manufacturing community as to how quickly they want to drive their own uptake in the market,” he said.

In the United States, it’s often lamented that biosimilar education is not as robust as it could be, and for that reason patients and physicians are not as well informed as they should be about the safety and efficacy of these agents, contributing to low levels of uptake.

The situation in Europe, for the most part, is the reverse, Sweeting said. “It’s for that reason that the market is actually so much more developed than it is in other parts of the world. The uptake over quite an extended period of time has been pretty significant. That said, there’s always more you can do.”

Sweeting said the company has regularly been involved in educational meetings “where we’re explaining what biosimilars are, how they’re produced, and the quality control mechanisms that we have in place.” In the Nordic countries, especially, biosimilar awareness is high and “there’s actually minimal amounts of work needed at the physician level—the system really drives the uptake,” he said.

In response to a query whether the European regulatory approval process for biosimilars has slowed down because of the COVID-19 pandemic, Sweeting said it appears not.

“What we have seen, day to day, and through our work with our commercial partners, is that there have been some contracting processes or issuance and decision-making of tenders in particular countries that have been delayed to some extent. Regulatory-wise, we haven’t seen a delay, certainly, for the bevacizumab cycle that we’ve just been through.”

As the worldwide business community has gotten accustomed to low-transmission safe practices during COVID-19, the door has reopened to actual physical interaction—based sales promotions, but only slightly, Sweeting said.

“Most of Europe has had to stay remote in their interactions with customers, and that is still primarily the case now. We have seen some opening of face-to-face contact and access in certain parts of Europe—Germany is one we’ve seen a bit of movement in, and in France and Italy from a major market perspective, but they are the exception rather than the rule at this stage. And there’s to some extent a second wave [of COVID-19] hitting many countries around the world,” Sweeting said.

“I personally think that the remote interaction that is or has become the norm over the last 6 months or so will continue to be the case, and that is something that, for sure, our partners are heavily reliant upon as well.”

Some European markets are more formidable than others with regard to complexity and getting biosimilars established, but there are good places to start, Jonathan Sweeting, head of Europe for Samsung Bioepis, explains.

Samsung Bioepis Exec Discusses European On-Ramp for Aybintio 

A review of changes in business practices by pharmacy benefit managers (PBMs) states that apparent reforms have been undermined by behind-the-scenes arrangements that locked in outsized profits for these organizations and undermined efforts at greater value for health care consumers and other stakeholders.

These practices have stalled placement of biosimilars on formulary and slowed uptake, giving preference to more costly originator drugs, the authors 

“With few exceptions, biosimilar uptake among PBMs has been slow. Formulary decisions on brand drugs, sometimes touted as innovative cost-saving measures, are often unrelated to clinical value and may be implemented for products without any available comparative evidence of clinical or cost-effectiveness, suggesting that rebates influence them,” the authors wrote.

In 2019, PBMs responded to “intense public criticism” by introducing measures designed to increase transparency and reduce costs for health plan sponsors; however, the PBM business models that introduced changes that were “mostly cosmetic,” the authors pointed out.

They contend that PBMs have managed to retain a hefty “spread” between what they pay pharmacies for prescription volume and what they collect from employers. In Florida Medicaid programs in 2018, the state’s 5 largest PBMs “collected 28% of prescription drug profit despite dispensing only 0.4% of claims,” partly by shifting business toward PBM-owned pharmacies, the authors stated.

Many contract provisions and terms in PBM contracts may obscure the true picture of where the money is flowing, they said.  

“PBM contracts with payers typically lack important detail about revenue received from manufacturers and pharmacies, drug-pricing methods, and dispensing costs at PBM-owned versus community pharmacies. Without such information, plan sponsors may be unaware of financial misalignments, such as whether the pharmacy network has been chosen based on the lowest cost to the plan sponsor or the highest financial yield to the PBM,” the authors said.

“Plan sponsors may also be unaware that multiple sources of manufacturer revenue may be excluded from the 100% pass-throughs they receive or that the PBM may use a separate group purchasing organization to aggregate and distribute rebates, potentially allowing additional revenue retention,” they wrote.

PBM contracts have evolved significantly since the 1980s when they provided important advantages for employers, such as pharmacy carve-outs, or tailored reimbursement, and automated claims processing and favorable discounts for mail order, the authors described. PBMs acquired greater influence with the rapid increase in drug spending caused by blockbuster drug launches, coverage expansions, and broader definitions of chronic diseases. Gradually, key business arrangements such as network contracting, price negotiation, and formulary coverage were delegated to PBMs.

Employers have become heavily dependent on PBMs for leverage over manufacturer cost increases. The US price of adalimumab is 96% higher than in the United Kingdom (2 syringes, $2669 vs $1362, respectively), and the US price of bevacizumab is 736% higher (400 mg, $3930 vs $470), the report said.

“Pricing is based on what the market will bear, not on the producer’s cost,” the authors stated. Passage of the Affordable Care Act resulted in rapid increases in specialty drug costs because it mandated coverage “in every US pharmacopeia class and included no price controls,” they said.

The authors recommend that plan sponsors gain insight into how PBMs are functioning by “following the money” and paying close attention to “conflicted revenue streams and information asymmetry.”

 over their practices. In June 2020, the Pharmaceutical Care Management Association (PCMA), which represents PBMs, fought back with a survey that said 93% of employers (9 in 10) “are satisfied with their PBM, including more than a third who are ‘very satisfied.'"

“Our survey finds that benefit managers are overwhelmingly satisfied with their organization’s PBM, saying that the contracts are transparent, and that PBM programs are effective at reducing their organization’s drug costs,” said Dan Judy, vice president at North Star Opinion Research, which conducted the 

Motheral BR, Fairman KA. Changes in PBM business practices in 2019: true innovation or more of the same? 

. Published online September 1, 2020. doi:10.18553/jmcp.2020.20213

It’s same old, same old when it comes to pharmacy benefit manager (PBM) contracts despite much touted reforms, authors of a review contend.
 

Report: PBM "Reforms" Leave Biosimilars Out in the Cold

Biocon Biologics and Mylan said they have launched the long-acting insulin glargine product Semglee on the US market and hope to obtain formal biosimilar status for it. Semglee was 

 in June as an equivalent to Sanofi’s Lantus insulin glargine, but not as a biosimilar, owing to the regulatory pathway taken.

It has been launched at a deep discount to the reference product and arrives at a time of great pushback against high insulin prices and limited competition. Many public and private health plans have been lowering out-of-pocket costs for patients to ensure access to this essential medicine.

Available in vials and prefilled pens, Semglee is for the control of high blood sugar in adult and pediatric patients with type 1 diabetes and in adults with type 2 diabetes. It is not recommended for patients with diabetic ketoacidosis.

Although considered a biosimilar in other markets, Semglee doesn’t exactly qualify as such in the United States. It was approved via a new drug application under the Hatch-Waxman Act, a pathway traditionally used for generics and some biologics, including insulins. Because insulin approvals are now governed by the Biologics Price Competition and Innovation Act (BPCIA), and have been since March 2020, Semglee is now “deemed” a biologic.

“We are proud to be the first company, following the reference product, to receive FDA approval on and launch both the vial and pen presentations of an insulin glargine treatment with an identical amino acid sequence to Sanofi's Lantus,” said Mylan CEO Heather Bresch. She 

 the potential market for Semglee at 30 million Americans.

Mylan said it aims to have Semglee declared a full-fledged biosimilar to Lantus and has filed “all necessary documentation” to the FDA under the 351(k) pathway, which is the official BPCIA route for biosimilar approval. In addition, Mylan said it “remains confident in seeking an interchangeability designation” for the product as well.

Interchangeable designations allow pharmacists to fill prescriptions with biosimilars without consulting the prescribing physician. No current biosimilars have the interchangeable designation. It has been argued that there is such a high level of comfort with the safety and efficacy profile of insulins that approved products should be treated as interchangeable with originator products. Interchangeability would also speed the uptake of competing products.

To boost market acceptance of Semglee, Mylan, which serves as Biocon Biologics’ distribution partner in the United States, is offering packages of five 3-mL Semglee pens at the wholesale price of $147.98 and 10-mL individual vials at $98.65, which it called the lowest wholesale costs for any long-acting insulin glargine on the market.  

“The list price of Semglee pen is equivalent to the Lantus launch price in 2007, and the Semglee vial is listed at Lantus’ 2010 pricing,” Mylan said in a statement. The individual vial cost of Lantus has climbed from $244 in 2013 to $431 in 2019, a 77% increase, according to a Senate Finance Committee 

Patient assistance programs or co-pay cards may further lower the cost, the statement said.

“We believe the US market represents a great opportunity for us and expect Semglee to contribute significantly to our goal of impacting 5 million patient lives and achieving $1 billion revenue by end of [fiscal year 2022],” said Christiane Hamacher, CEO of Biocon Biologics.

Semglee was approved based on analytical, preclinical, and clinical studies that confirmed the pharmacokinetics and pharmacodynamics, efficacy, safety, and immunogenicity of Semglee in comparison with Lantus in patients with type 1 and type 2 diabetes.

For all intents and purposes, Semglee is a biosimilar insulin, but official biosimilar status is needed to clinch the marketing aspect.

Biocon, Mylan Launch Semglee and Seek Biosimilar, Interchangeable Status 

Continuing with its string of recent biosimilar launches, Cadila Pharmaceuticals has put an adalimumab biosimilar (Cadalimab) on the Indian market. The drug is available in a prefilled syringe, 40 mg/0.8 ml.

Adalimumab is an antirheumatic drug for the treatment of arthritis, plaque psoriasis, ankylosing spondylitis, Crohn disease, and ulcerative colitis. It references Humira, an AbbVie product, which had net revenues in 2019 of $19.2 billion, $14.9 billion of that in the United States, where the product does not yet face biosimilar competition. By binding with tumor necrosis factor-alpha, the drug helps to prevent inflammation.

There is a potentially large market for Cadalimab. Cadila, based in Ahmedabad, India, noted that roughly 7 million individuals in India have rheumatoid arthritis (RA) and 2.8% of the population has psoriasis. Adalimumab is currently marketed in over 60 countries by multiple companies, according to Transparency Market Research, which 

that the high cost of adalimumab ($2000-$3000 per month) is a barrier to uptake.

In the United States, 6 adalimumab biosimilars have been approved but market entry is not anticipated for any of them before 2023, owing to product exclusivity rights. Mordor Intelligence has forecast an anual growth rate for the adalimumab of 5.1% through 2025, 

the fastest growth for adalimumab biosimilars in the Asia Pacific region, including India and China, where health care consumers are highly responsive to price changes.

“While these are not life-threatening, psoriasis and RA can be painful to live with. With the launch of Cadalimab,

we want to reach these patients with a cost-effective solution and give them a chance at a better life,” Amit Ajmera, company vice president, said in a 

Cadila noted this marks the fourth biosimilar launch in the past 2 months. In early August 2020, Cadila launched a 

 biosimilar (NuPTH), referencing Lilly’s Forteo, for the treatment of osteoporosis.

 a rituximab (Ritucad), for the treatment of blood cancer, including non-Hodgkin lymphoma, and rheumatoid arthritis, and a bevacizumab (Bevaro), for the treatment of ovarian cancer, glioblastoma multiforme, colorectal cancer, breast cancer, lung cancer, cervical cancer, and kidney cancer. The rituximab biosimilar references Rituxan (Biogen) and the bevacizumab biosimilar, Avastin (Genentech).

Cadila, one of the largest privately held pharmaceutical companies in India, suggested it may have more biosimilar products to launch later this year.

With the launch of an adalimumab, Cadila hopes to get a piece of the worldwide biosimilar market for antirheumatic treatments.

Cadila Launches Fourth Biosimilar in 2 Months

Dan Leonard, former president and CEO of the National Pharmaceutical Council (NPC), has been 

 president and CEO of the generic and biosimilar industry trade group Association for Accessible Medicines (AAM), effect September.

He succeeds Chester “Chip” Davis Jr, who left AAM in February 2020. AAM represents manufacturers and distributors of generic pharmaceuticals, biosimilars, and bulk pharmaceutical chemicals. Its membership includes suppliers of other goods and services to the generic industry.

Within AAM is the Biosimilars Council, which works to improve biosimilar awareness and uptake with an emphasis on public and health expert education, government affairs, legal affairs, and regulatory policy.

At the NPC, Leonard helped with the group's mission to develop pharmaceutical and pharmaceutical innovation through research and sponsorship of research. Previously, Leonard was executive vice president of advocacy and professional services for America’s Health Insurance Plans, a trade association that represents US payers.

He is a regularly published columnist with 

, Leonard highlighted the challenges to ensuring access to health care for populations affected by coronavirus disease 2019 (COVID-19). He predicted increased Medicaid enrollment leading to challenges for states with limited budgets.

Members of AAM expressed confidence in Leonard’s abilities to lead group toward greater success. “Dan’s decades of leadership experience across the pharmaceutical ecosystem and his unparalleled background in policy and communications make him the perfect person to lead our industry’s efforts to advocate for policies to increase patient access to generic and biosimilar medicines through greater competition,” said Alok Sonig, chairman of the AAM Board of Directors and CEO, US Generics and Head, Global R&D and Biosimilars, Lupin.

Leonard’s background includes more than 20 years of experience in strategic communications, legislative management, politics, and broadcast journalism. During the search for Davis’ replacement, AAM was helmed by its senior vice president and general counsel, Jeff Francer.

The Association for Accessible Medicines, which represents generic and biosimilar manufacturers, chose a leader with a research, public relations, and strategic planning background.

Dan Leonard Takes Helm of Association for Accessible Medicines

The first of the Canadian provinces to implement a mandatory biosimilar switching policy, British Columbia (BC), has initiated a new phase of the program this month. Residents enrolled in the PharmaCare prescription coverage plan who are receiving the reference version of rituximab (Rituxan) will be switched to 1 of 3 biosimilar versions (Truxima, Riximyo, Ruxience).

On the cusp of the transition, officials in the BC public health system 

 the success of their biosimilars switching program thus far, saying it had saved millions of dollars that were plowed back into other health initiatives that have improved access for many patients of the Pacific Coast district, which has roughly 5 million residents.

“We have seen great successes with our Biosimilars Initiative, with thousands of patients transitioning to safe and equally effective biosimilar drugs,” said Adrian Dix, minister of health.

Mandatory switching programs in Canada have not met with unanimous support, as many residents and patient advocates have expressed 

 about what switching may mean for the stability of their managed conditions. Health officials in Canada, however, say they remain confident in the medical science that supports biosimilars as equivalent in safety and efficacy to their reference products. The BC PharmaCare system does allow for exceptions to mandatory switching.

“We take great care here in British Columbia to examine the evidence thoroughly,” Dix said.

In the first phase of the program, which began in May 2019, patients were switched from etanercept, infliximab, and insulin glargine reference products to biosimilars. These switches occurred only for patients receiving treatment for ankylosing spondylitis, rheumatoid arthritis, psoriatic arthritis, plaque psoriasis, and diabetes (type 1 and type 2).

In the second phase, which began in September 2019, patients with Crohn disease and ulcerative colitis were switched from reference infliximab to biosimilar versions.

The current switch to rituximab biosimilars, which constitutes the third phase, affects patients undergoing treatment for granulomatosis with polyangiitis, microscopic polyangiitis, relapsing-remitting multiple sclerosis, and rheumatoid arthritis.

Dix said that biosimilars cost 25% to 50% less than biologics, which account for the largest slice of the health-spending pie, so the 15-month-old switch to biosimilars in BC is already paying off with huge savings. In 2018, BC spent $84.2 million on reference infliximab, so the incentive to switch to biosimilars was very strong.

“This work is allowing us to put another $30.7 million over the next 3 years, in addition to the $96.6 million from earlier phases of the Biosimilars Initiative, back into BC’s health care system,” Dix said.

On the whole, biosimilars have barely penetrated the health care system in Canada, where they have an 8% use rate. Dix noted that countries that are furthest ahead with biosimilars enjoy usage rates from 50% to 95%.

Nevertheless, in BC, the switching rates achieved through the Biosimilars Initiative are impressive. Among PharmaCare patients who were taking etanercept reference product, 85% have switched to Brenzys or Erelzi. For patients taking Remicade for nongastrointestinal and gastrointestinal issues, 84% and 78% have switched, respectively; and 71% of patients have been transitioned from Lantus to Basalgar for their diabetes conditions.

In the United States, by contrast, biosimilars account for just 2.3% of spending in the biologics marketplace, according to a recent 

 by Juliana Reed, MS, a vice president and Global Corporate Affairs lead for Pfizer; and biosimilar infliximab accounts for just 8.5% of the infliximab market, 

 to Wayne Winegarden of the Pacific Research Institute. Filgrastim biosimilar sales in the United States are highly advanced, relative to other biosimilar products. They amount to 50.4% of expenditures for infliximab.

The May 2019 phase 1 transition involved 20,700 British Columbians and allowed them 6 months to work with their health care advisors to transition from originator products. Phase 2 involved 2000 patients, who were given the same transition time. The current, rituximab changeover also involves a 6-month deadline—until February 2021&mdash;and roughly 1600 patients.

The savings have not only made care more affordable, but also broadened access to care in BC, Dix said. “The savings have allowed expanded coverage of treatments for chronic obstructive pulmonary disease and attention deficit hyperactivity disorder in adults, and treatments that mitigate the risk of heart attack or stroke.”

The statistics show that for the Rocky Mountain province, biosimilar savings are pouring into the health care system and allowing for significantly greater access.