The Center for Biosimilars Staff

 that the FDA will review data supporting the firms’ Biologics License Application for ABP 215, a 

The FDA Advisory Committee will review the analytical, pharmacokinetic, and clinical data from studies on ABP 215, including the results of a phase 3 study that met its primary endpoint of demonstrating clinical equivalence to the reference product in patients undergoing treatment for non-squamous, non-small cell lung cancer. The study also demonstrated comparable safety and immunogenicity profiles for ABP 215 and the reference bevacizumab. 

 that they believe their product to be the first bevacizumab biosimilar submitted for consideration in the United States, the reference product’s manufacturer, Roche, sees competition brewing in Europe—the European Medicines Agency has 

 that it is currently considering 2 applications for bevacizumab biosimilars. 

Roche, in attempting to retain its hold on the 

 bevacizumab market, has asserted that its patent protection for bevacizumab extends until 2019. The firm filed a complaint in the US courts in response to Amgen and Allergan’s application, and seeks to bar the biosimilar product from the US market until the patent dispute has been resolved. 

Roche’s argument hinges upon the so-called “patent dance” requirements as laid out in the Biologics Price Competition and Innovation Act. However, after this week’s Supreme Court ruling in 

, which held that the “patent dance” is optional, Roche may be forced to change its litigation approach. 

Articles

Last week, Amgen and Allergan announced that the FDA will review data supporting the firms' Biologics License Application for ABP 215, a bevacizumab (Avastin) biosimilar candidate. 

FDA to Review Bevacizumab Biosimilar, While Roche Hopes to Defend Its Patent

In a big win for Sandoz, the US Supreme Court ruled 

 that a manufacturer of a biosimilar product can provide a notice of commercial marketing either before or after FDA approval of the drug to the reference drug developer. The court also rejected the Circuit court’s 2-tier timing interpretation for the 180-day marketing notices to the FDA.

In its decision today, which was delivered by Justice Thomas on behalf of the Supreme Court, the court also said that there is no injunction available under federal law to force compliance with the patent dance, but it might be available under state law—a question that the Circuit Court could address.

 filed by Amgen—which developed and markets filgrastim (Neupogen)&mdash;against Sandoz, which has developed the biosimilar filgrastim-sndz (Zarxio), states that Sandoz did not exchange patent and manufacturing information with Amgen about it’s biosimilar. Sandoz’s attorney Julia Pike, the company decided to forego the patent dance and tried to speed the process of resolving any patent issues related to marketing Zarxio.

“The Justices’ unanimous ruling on the notice of commercial marketing will help expedite patient access to life-enhancing treatments. We also appreciate the clarity provided on the patent dance, which will help the biosimilars industry move forward,” said Carol Lynch, Global Head of Biopharmaceuticals, Sandoz, in a statement. “As the global leader in biosimilars, it is our responsibility to help eliminate barriers so patients can access more affordable medicine. The results of this Supreme Court case reinforce that the work we are doing every day has meaning to the patients and customers we are here to help.”

The pharmacy benefit manager Express Scripts also expressed support for the federal court’s decision, saying that the ruling will allow affordable access to medicine. “At a time when the cost of complex biologic specialty drugs is growing at double-digit rates, payers need every tool in their arsenal to bring cost-effective solutions to market. Express Scripts continues to champion for a clear pathway to expand the appropriate use of biosimilars. This ruling should help expand access and lower prescription drug costs for employers, health plans, labor unions, and Medicare,” according to the statement. Express Scripts also noted that, by its estimate, the United States "wasted more than $45 million for every month that the Sandoz biosimilar Zarxio (filgrastim-sndz) was delayed from coming to market as a result of the notice of commercial marketing issue argued in 

Sandoz, the manufacturer of the first biosimilars to be applied for and launched in the United States, as well as the first company to have 2 biosimilars approved by the FDA, said in its press release related to the ruling, "America spent $323 billion in 2016 on prescription medicines, and biologics are estimated to account for 28% of drug spending by 2020. One analysis predicted that biosimilars could deliver up to $44 billion in savings to the US healthcare system by 2024 while driving healthy competition and innovation." 

In a big win for Sandoz, the US Supreme Court ruled today that a manufacturer of a biosimilar product can provide a notice of commercial marketing either before or after FDA approval of the drug to the reference product developer.

SCOTUS Reverses Federal Circuit Court Decision in Sandoz v Amgen on 180-Day Rule 

A recent QuintilesIMS report shows that biosimilars have led to reductions in the price of biologics in Europe. Our infographic shows 4 key takeaways from the study. Read 

A recent QuintilesIMS report shows that biosimilars have led to reductions in the price of biologics in Europe. Our infographic shows 4 key takeaways from the study.View the infographic or read more about the report here.
 

Infographic: Biosimilars Lead to Price Drops in Europe

Today, the European Medicines Agency (EMA) released its June 2017 

 of medicines currently under evaluation, showing 4 applications under review for adalimumab, 2 applications for bevacizumab, 1 new application for infliximab, 1 application for insulin glargine, 3 applications for pegfilgrastim, and 4 applications for trastuzumab. 

Since the first of the year, the EMA has approved a number of biosimilar products: January saw the approval of Eli Lilly’s biosimilar to teriparatide (Foresto, Forteo), an osteoporosis drug. In February, Celltrion’s Tuxella (also 

 as Ritemvia, Truxima, and Blitzima), a rituximab (Rituxin) biosimilar, gained approval. March saw the approval of Amgen’s application for its adalimumab (Humira) biosimilar, while Merck marked April with its insulin glargine (Lantus) product. 

Europe continues to outpace the United States in biosimilar product approvals; while the FDA was first to approve an adalimumab biosimilar, the EMA’s March approval granted to Amgen means that each originator biologic that has an approved US biosimilar now has a biosimilar approved in Europe. Yet the United States may be starting to catch up with the European marketplace; many of the same applications under review at the EMA are also under review at the FDA. Perhaps most notably, several companies are 

 to be first to introduce a pegfilgrastim (Neulasta) biosimilar to the US and European markets. 

Coherus submitted its application for pegfilgrastim to the FDA in August of 2016, following applications by Sandoz in 2015 and Apotex in 2014. Sandoz, for its part, suffered a disappointment when the FDA rejected its application for pegfilgrastim biosimilar, and industry 

 say that Sandoz’s US product approval may be delayed until 2018. Meanwhile, Sandoz withdrew its application from the EMA. Apotex hopes to beat its competitors to market, and issued a 

 to the FDA in May asking the agency to require all proposers of pegfilgrastim biosimilars to conduct appropriate studies for their products (noting that Coherus, in particular, has not yet studied its proposed product in any diseased patients for indicated uses). 

In addition to applications for pegfilgrastim, both the FDA and EMA are 

 biosimilar applications for trastuzumab (Mylan and Biocon),  bevacizumab (Amgen and Allergan), and adalimumab (Boehringer Ingelheim).

A newly streamlined approvals process for biosimilars in the FDA may begin to close the gap between the US and European biosimilars approvals; when the FDA approved Samsung Bioepis’s infliximab-abda (Renlexis) in early 2017, it was the first time that a biosimilar product had been approved in the United States without a public advisory committee meeting; the agency 

 that it would hold only 1 such meeting for the first approved biosimilar of a reference product, a move that could speed up the approvals process for future applications. 

Today, the European Medicines Agency (EMA) released its June 2017 list of medicines currently under evaluation, and many of the biosimilars are also under consideration by the FDA.

EMA's Biosimilar List Includes Drugs Also Under FDA's Scrutiny

The Center for Biosimilars (CB) interviewed Brian Lehman, MBA, MHA, RPh, manager of Pharmacy Benefits and Policy, Columbus, Ohio, and editorial board member of CB, to discuss challenges and opportunities in this rapidly developing field.

CB: What do you think is the best way to expand familiarity with biosimilars in the medical healthcare community?

 The medical healthcare community needs unbiased, comprehensive, up-to-date information on biosimilars.  They need information to fill gaps in knowledge:

Defining biologics, biosimilars and biosimilarity

Understanding the approval process and the US Food and Drug Administration’s (FDA’s) use of totality of evidence to evaluate biosimilars

Appreciation that the safety profile of a biosimilar is expected to be the same as that of the reference product

Understanding how decisions are made by the FDA for extrapolation of indications

Defining interchangeability and the related rules regarding pharmacy-level substitution

In order to expand familiarity with biosimilars, it will take multi-pronged communication strategies to be implemented by manufacturers.  Biosimilar manufacturers, especially those who currently have biosimilar products in the market, have a large responsibility in expanding familiarity with biosimilars in general as well as for their specific product(s). 

Other stakeholders are key to helping expand familiarity with biosimilars. The Academy of Managed Care Pharmacy's 

 offers educational resources and information on biosimilars to health care providers and other stakeholders. The 

 provides resources and educational events.  The FDA provides 

CB: How can the oncology community in particular benefit from extended knowledge of biosimilars and, conversely, benefit the biosimilar industry?

 The more knowledge that the oncology community has on the safety and effectiveness of biosimilars as well as answers to gaps in knowledge, the more the community will have confidence and acceptance of biosimilars. This increased confidence and acceptance by providers and patients will then translate into manufacturers capturing higher sales and market share for their biosimilars. 

The oncology community is currently impacted by one biosimilar Zarxio (filgrastim) that has been available on the market since September 2015. Zarxio, the biosimilar for Neupogen, is a granulocyte colony-stimulating factor that stimulates the growth of neutrophils that are important in the body’s fight against infection. Note that the FDA has currently approved only 5 biosimilars.

The oncology community will be impacted in the future with additional biosimilars for Neupogen, Neulasta and Procrit/Epogen. Additionally, the first biosimilar to Herceptin (used to treat certain HER-2 positive breast and gastric cancers) as well as the first biosimilar to Avastin (used for non-small cell lung cancer, renal cell cancer, metastatic colorectal cancer and other region-specific indications) are currently being reviewed by the FDA.

The biosimilar pipeline is robust; the FDA has 66 biosimilars programs enrolled for 20 different reference products

John Jenkins, the director of the FDA’s Office of New Drugs, 

CB: Do you believe that biosimilar treatment options will make treatment more affordable?

 Yes, biosimilar treatment options will make treatment more affordable for patients. Initially, we have seen that when only one biosimilar product is available on the market, it is priced 15% off the reference product list price (for example, Zarxio priced 15% off the list price of Neupogen). 

Biosimilars will be at least 10% to 30% less than the reference product. The potential for cost savings will vary across biologic drug classes based upon factors such as sales, degree of competition and timing of biosimilar entry. 

I believe in the future, when several competing biosimilars to the same reference product are available in the market, the discounts will likely exceed 30% less than the reference product. The even larger savings and affordability that providers and patients are looking for will come to fruition when multiple competing biosimilars are available in the US market.

Biosimilars will help reduce healthcare premiums as well as out-of-pocket costs (such as deductibles and copays) that are mostly being driven by biologic drugs. The biosimilars market is expected to create anywhere from $44 to $250 

in health systems savings over 10 years (2014-2024) according to various estimates.

CB: What would be the best-case scenario for biosimilar incorporation into mainstream medicine from a healthcare policy/cost perspective?

 Ideally, healthcare policy will support a robust biosimilar marketplace which will ultimately lead to improved patient access to more affordable biologics. Manufacturers will continue to need a policy environment that will encourage them to develop biosimilars, such as removing the barrier of restricted access to some reference products that prevent manufacturers from developing competing biosimilars (this could be addressed through the FAST Generics Act or CREATES Act)

 and drug patent battles that delay biosimilars from entering the market even after FDA approval.

From a cost perspective, ideally biosimilars will provide significant savings relative to the cost of the reference product, in order to help improve patient access.  But, there is a need to balance and monitor for the potential unintended consequence of discouraging some manufacturers from bringing more biosimilar competition to the US market.

CB: What, in your opinion, is the greatest benefit represented by biosimilar uptake?

 The greatest benefit would be increasing patient access to more affordable life-changing and even life-saving biologic drugs. Hopefully we will see this happen in the US as was seen in the UK in 2009, when within 3 years of the introduction of the biosimilar filgrastim, patient access to filgrastim nearly doubled.

CB: Do you recognize the need for educating healthcare professionals and patients on biosimilars?

 Yes! Education on the safety and effectiveness of biosimilars is a key component to the success of the biosimilars market. This was one of the keys to increasing generic drug utilization post Hatch-Waxman Act and has contributed significantly to the 89% generic drug utilization in the US.

Healthcare professionals need education in order to have a better understanding and knowledge of biosimilars, so that they feel comfortable about administering biosimilars to patients. Healthcare professionals need unbiased, comprehensive, up-to-date information on biosimilars. 

Patients need education in order to feel confident that a biosimilar is just as safe and effective as the reference product.  They need to know information such as the FDA has stringent product approval standards for biosimilars and that biosimilars have an established international track record.  Europe has experienced over 400 million patient days of safe and effective treatment using biosimilars since the first biosimilar was approved and marketed in 2006.

1. Cohen H, Beydoun D, Chien D, et al. Awareness, knowledge, and perceptions of biosimilars among specialty physicians. 

2017;33(12):2160-2172. doi: 10.1007/s12325-016-0431-5.

2. Welch AR. How to make the most of your FDA biosimilar meetings. Biosimilar Development website. 

https://www.biosimilardevelopment.com/doc/how-to-make-the-most-of-your-fda-biosimilar-meetings-0001

. Published November 14, 2016. Accessed April 25, 2017. 

3. Mulcahy AW, Predmore Z, Mattke S. The cost savings potential of biosimilar drugs in the US. RAND Corporation website. 

https://www.rand.org/content/dam/rand/pubs/perspectives/PE100/PE127/RAND_PE127.pdf

. Published November 2014. Accessed April 25, 2017. 

4. The $250 billion potential for biosimilars. Express Scripts website. 

http://lab.express-scripts.com/lab/insights/industry-updates/the-$250-billion-potential-of-biosimilars

. Published April 23, 2013. Accessed April 25, 2017. 

5. Brennan Z. ‘FAST’ Generics Act seeks to thwart abuse of FDA safety programs. Regulatory Affairs Professionals Society website. 

http://www.raps.org/Regulatory-Focus/News/2017/04/10/27309/‘FAST’-Generics-Act-Seeks-to-Thwart-Abuse-of-FDA-Safety-Programs/

. Published April 10, 2017. Accessed April 25, 2017. 

6. Brennan Z. US Supreme Court to consider biosimilar patent process next week. Regulatory Affairs Professionals Society website. 

http://www.raps.org/Regulatory-Focus/News/2017/04/20/27383/US-Supreme-Court-to-Consider-Biosimilar-Patent-Process-Next-Week/

. Published April 20, 2017. Accessed April 25, 2017. 

7. AbbVie v Amgen. Big Molecule Watch website. 

http://www.bigmoleculewatch.com/abbvie-v-amgen/

. Published October 14, 2016. Accessed April 25, 2017. 

8. Walsh K. Biosimilars’ utilization and the role payers do play in driving uptake in Europe: an industry perspective. Paper presented at: Biosimilar Medicines 11

 EGA International Symposium; April 25-26, 2013; London, UK. Accessed April 25, 2017. 

9. Association for Affordable Medicines: 2016 annual report. AAM website. 

http://accessiblemeds.org/wp-content/uploads/2017/02/AAM-Annual-Report-2017.pdf

. Published February 2017. Accessed April 25, 2017. 

10. Did you know?: biosimilar medicines. Medicines for Europe website. 

http://www.medicinesforeurope.com/biosimilar-medicines/did-you-know/

. Published March 2016. Accessed April 25, 2017. 

Biosimilar Uptake Implies Patient Access to Affordable Medication

The Center for Biosimilars (CB) interviewed Joseph P. Fuhr, Jr, PhD, professor emeritus, Widener University, and editorial board member of 

 What would be an ideal way to expand familiarity with biosimilars within the medical healthcare community?

 Educational programs are the best way and this includes such entities as the FDA, pharmaceutical companies, and payers to educate physicians and patients.

 How can the oncology community in particular benefit from extended knowledge of biosimilars and, conversely, benefit the biosimilar industry?

 Oncology drugs are some of the highest priced drugs. Biosimilars can decrease the price of these drugs, thus increasing access and improving the quality of life of more patients. 

 Do you believe that biosimilar treatment options will make treatment more affordable?

 Yes. Competition will lead to lower prices and we have seen this in the European Union.

 What would be the best-case scenario for biosimilar incorporation into mainstream medicine from a healthcare policy/cost perspective?

 As patents expire and more biosimilars enter [the market], prices will decrease. It will take a while for the market to fully develop.

 What, in your opinion, is the greatest benefit represented by biosimilar uptake?

 Lower prices and greater access, which will benefit consumers and help decrease prices in the healthcare market. Also, it will result in innovators’ attempting to find benefits on new drugs as profits on old drugs decline. Biosimilars will thus benefit society.

 Do you recognize the need for educating healthcare professionals and patients on biosimilars?

 Many patients and physicians are unaware of what biosimilars are and the process that they must go through to achieve FDA approval. People are not going to purchase or prescribe something which they do not understand.

 Would biosimilars raise challenges with formulary management for health plans and for clinical pharmacies?

 Any time a new alternative comes to market, formulary management and clinical pharmacies must make a decision on the circumstances under which they will adopt the alternative. So, they must decide on the quality and price of the product to determine not only if it will go onto the formulary but also on what tier in terms of health plans.

Dr Joseph P Fuhr Sees Need for Education Programs on Biosimilars

 to a second biosimilar to infliximab (Remicade, Johnson & Johnson). Infliximab-abda (Renflexis), an intravenous infusion developed by Samsung Bioepsis/Merck, has been approved for multiple indications.

This tumor necrosis factor (TNF) inhibitor has been indicated for various inflammatory conditions, including Crohn’s disease (adult and pediatric), ulcerative colitis, rheumatoid arthritis (combined with methotrexate), ankylosing spondylitis, psoriatic arthritis, and plaque psoriasis.

"Once Renflexis hits the market, it will be the first time we will see competition between 2 biosimilars, Inflectra and Renflexis, along with the reference product Remicade," said Brian Lehman, MBA, MHA, RPh, who is a manager of pharmacy benefits and policy in Columbus, Ohio. Lehman, who also serves on the editorial board of The Center for Biosimilars, added that Renflexis offers another important option for patients and providers in the treatment of serious inflammatory diseases.

The most common adverse reactions for infliximab-abda include infections, infusion-related reactions, headache, and abdominal pain, and its use is contraindicated with anakinra or abatacept. The label also indicates that the drug has not been evaluated in children under 6 years diagnosed with ulcerative colitis or Crohn’s disease.

Infliximab-abda will be available in single-dose vials containing 100 mg of lyophilized drug for a final reconstitution volume of 10 mL.

The first biosimilar to infliximab, infliximab-dyyb (Inflectra, Pfizer), was 

 in November 2016. While Pfizer struggled for a while falling the launch of the drug, the company’s biosimilar revenues 

 by 48% a year later—fourth quarter sales from Inflectra touched $61 million in 2016 (up from $30 million a year ago) despite the fact that the drug is being sold at only a 15% discount to Remicade.

Second Biosimilar to Infliximab Approved

Several studies on omalizumab (Xolair), currently manufactured by Novartis through a partnership agreement with Genentech, recently presented at the 2017 Annual American Academy of Allergy, Asthma, and Immunology (AAAAI) meeting in Atlanta, Georgia, demonstrated why biologic therapies are considered by many to be the “future” of care.

Omalizumab, an injectable medicine for patients 12 years and older for treating severe-to-persistent allergic asthma not controlled by inhaled corticosteroids (ICS), was approved by the 

 in 2003 only for asthma. The indication was modified several times over the next decade, and included a warning of “slightly higher risk of heart- and brain-adverse events,” which was added in September 2014. While the warnings may have changed, the uses for this flexible biologic drug have clearly only begun to be discovered.

“Despite the availability of omalizumab since 2003, utilization trends have not been previously described,” observed 1 research team, headed by Matthew Rank, MD, a physician at the Mayo Clinic in Scottsdale, Arizona. The team identified 8545 patients who used omalizumab between 2003 and 2015. They excluded certain conditions in order to prevent “censoring based on insurance coverage,” and noted that individuals starting on the biologic peaked in 2005 at 9.56 new users per 100,000 insured people and declined to 5.22/100,000 in 2012. In 2015, that number had climbed back up to 12.13/100,000, although 59% of those users stopped using the drug after less than a year.

The increased usage and relatively short duration of use could be due, in part, to aggressive marketing on the part of Genentech, which forecasters 

 at the end of Q1 2016 would own about 40% of 2016’s “top 10 new drugs in peak projected sales,” in large part due to its biologic and biosimilar research. Back in the 1990s, Genentech “officially committed to oncology” in the words of then-CEO Arthur D. Levinson, PhD, and that decision led the company toward biopharmaceutical research that, including breakthrough treatments for multiple sclerosis and, eventually, to omalizumab, which was a blockbuster drug in 2014. Genentech and Novartis ultimately endured a nasty scandal when whistleblowers accused them of marketing omalizumab directly to healthcare providers for wide-ranging uses instead of the narrow window of use prescribed by the FDA. The fact remains that omalizumab usage spiked and has remained high since.

Perhaps more exciting than the usage study was a study indicating that baseline blood eosinophil levels and asthma exacerbations could be reduced in children with moderate-to-severe allergic asthma through use of omalizumab. This is particularly intriguing since FDA restrictions on using the drug in children under 12 have been problematic for both drug manufacturers and physicians wishing to treat pediatric patients who are not responding to other therapies, including ICS, with omalizumab. The researchers, led by author Stanley Szefler, MD, a physician at the Children’s Hospital in Colorado and a professor at the University of Colorado School of Medicine in Aurora, Colorado, conducted a 24-week inhaled steroid dose-stable phase of a double-blind, randomized, controlled trial in children 6 to 12 years of age with “inadequately controlled, moderate-to-severe, allergic asthma.” They reported, “Clinically significant asthma exacerbation rates were reduced by 31% (

 = .007) with omalizumab versus placebo. The study not only demonstrated a pediatric usage that might be beneficial to a younger age group, but also provided a method for physicians to predict how younger patients might respond to the treatment, since children with elevated baseline eosinophil counts ≥300µ showed a “significantly greater response” to the drug compared with placebo, while children with lower baseline eosinophils had “nonsignificant reductions.”

Finally, another group led by Shaun Kilty, MD, a physician in the University of Ottawa Hospital’s Otolaryngology-Head and Neck Surgery, presented evidence that omalizumab treatment “provided significant improvement in every major clinical symptom of chronic rhinosinusitis (CRS),” although the group emphasized that “a well-designed clinical trial is needed to further assess the efficacy and safety” of the treatment. The group evaluated 25 patients diagnosed with CRS and 5 control patients who would have qualified for the study but could not get insurance coverage for the treatment. The patients were treated for a mean duration of 19 months, and 76% had CRS with polyps while 33% had aspirin exacerbated respiratory disease. “The omalizumab therapy provided a mean overall symptom improvement of 69.5%,” Kilty reported, noting that this meant patients who received the omalizumab treatment experienced less facial pain, fewer nasal obstructions, and improvements in rhinorrhea and olfaction, while the control group, which also improved overall, experienced far less improvement.

These 3 studies, in conjunction, clearly demonstrate why biologic and biosimilar drugs represent such promise for pharmaceutical companies and for the fields of asthma, allergy, and immunology. With biologics and monoclonal antibodies (mAbs) in particular making up nearly a fifth of the asthma pipeline alone, according to business intelligence firm 

, these drugs often represent new options to patients with the most sensitive immune systems who have high levels of intolerance for many of the more “traditional” pharmaceutical options. One GBI analyst observed of the firm’s data, “Drug developers are looking to follow the example of Xolair by developing highly-targeted biologics and mAbs aimed at specific patient subtypes with the hope of benefiting previously underserved patients and generating strong revenues.” Another benefit of this strategy is that biologics often target pathogenesis that is relevant to multiple conditions, thereby opening up new uses for drugs in the future, as is currently the case with omalizumab.

Omalizumab Biologic is Changing the Face of Asthma Therapeutics

 as early as April 2017 for sale by Sanofi and Regeneron Pharmaceuticals, Inc, under the brand name Dupixent, made headlines with another positive study indicating that the investigational human monoclonal antibody (mAb) intended to treat moderate-to-severe atopic dermatitis (AD) shows “sustained efficacy in reducing signs and symptoms and improving skin lesions and pruritus among AD patients without any major safety issues.”

Lead author on the study, Mette Deleuran, PhD, professor in the Dermatology Department at Aarhus University Hospital in Aarhus, Denmark, and her team revealed their results in a late-breaking abstract session at the 2017 annual American Academy of Asthma, Allergy, and Immunology (AAAAI) meeting in Atlanta, Georgia, on March 6. Deleuran and her team 

 the first-step analysis from an ongoing phase 3 multi-center, open-label trial of subcutaneous dupilumab that Elias Zerhouni, former head of the National Institutes of Health and current Sanofi Pasteur head of Research & Development, described as “an illustration of something more profound [than a single-product success], which is really the emergence of a new science and portfolio at Sanofi.” He went on to call dupilumab the “prototype of future medicine” in an interview with 

 because it is designed to target 2 different disease pathways at the same time: cytokines IL-4 and IL-13, both of which are believed to signal the body’s immune system to respond, resulting in inflammation and symptoms typical of the disease.

Although Sanofi is waiting on specific approval for dupilumab for treating atopic dermatitis, effective inhibition of these cytokines and the immune responses that they trigger would indicate broader reach of the drug. From a profit standpoint, it could solidify the potential in the biosimilar sector, demonstrating that the success of a single drug for a single purpose opens up what Zerhouni calls “a pipeline in a single drug,” since many of these cytokines play a role in everything, from seasonal allergies to cancer.

According to the study, adults with moderate-to-severe AD who had participated in previous dupilumab trials were eligible to participate in phase 3 of the trial. Of the 1491 patients (60% male, with an average age of 39.7 years) who received treatment, 106 withdrew from the study during a 1-year perios. There were no deaths reported in the study. “The most common adverse events (AEs) were nasopharyngitis (20.5% of patients), upper respiratory tract infection (9.5%), exacerbation of the condition (8.2%), and conjunctivitis (all etiologies 10.7%)” the team reported. Patients who withdrew cited AEs, with the most common being nasopharyngitis, headaches, and upper respiratory tract infections. At the week-52 assessment in the study, 48.6% of patients had a score between 0 and 1 on the Investigator’s Global Assessment (IGA) 

 for their symptoms with a “1” score being “almost clear” and a “0” being “clear;” 75.4% achieved ≥75% in eczema area and severity, and their pruritus scores decreased by 62.24%. The patients came from multiple parent studies and efficacy did not differ across the board.

Sanofi spent about $5.47 billion on research and development last year, all of which could pay off once dupilumab is approved for marketing in the United States this year. According to Zerhouni, biologic drugs account for two-thirds of Sanofi’s pipeline of experimental medicines, and if dupilumab is approved, it is likely that Sanofi, which has been considered somewhat of a laggard in recent years in the research-and-development sector, could suddenly find itself setting the precedent for future spending allocations across the industry, despite the fact that biologics have been considered a bigger risk than traditional pharmaceuticals because they are more expensive to develop, manufacture, and get approved. The next step will be to “persuade healthcare providers to pay for dupilumab,” observed 

 reporter Ben Hirschler. However, such difficulties could be well worth it if the drug company finds itself not only leading the pack in eliminating AD symptoms, but also ahead of the game as a result of dupilumab in many other areas of treatment as well.

Dupilumab Improves Signs and Symptoms of Atopic Dermatitis Without Safety Issues

Patients treated with humanized monoclonal antibodies (mAbs) do not tend to have adverse events (AEs) to the treatments and, when they do, they are mild, reported researchers presenting their findings at the 2017 annual American Academy of Allergy, Asthma, and Immunology (AAAAI) meeting in Atlanta, Georgia, on March 5.

“We wanted to characterize the hypersensitivity and infusion reactions that cause a change in the treatment of patients receiving mAbs,” explained Dasha Roa-Medellin, MD, a physician in the Department of Allergy at the Hospital General Universitario Gregorio Maranon, Madrid, Spain. “The real incidence of [these reactions] is unknown,” she added.

Given that biosimilars for mAb treatments, themselves biologic in nature, are considered by many 

 in the field to represent a sustainable, financially-viable, treatment-crucial option for the future of “treating life-threatening conditions in all disease areas.” In their article published in the European Society for Medical Oncology (ESMO)’s 

 journal, the authors write that mAb treatments are relatively rare, seldom necessitate treatment modifications, and are relatively easy to respond to, all of which is highly promising for the biosimilar research space. mAb treatments are particularly common in oncological therapies, where many patients must deal with compromised immune systems on an ongoing basis. The lack of allergic reactions, overall, to the mAb treatments is promising for biosimilars such infliximab, which was included in the AAAAI study.

Roa-Medellin and her research group conducted a retrospective study that included 5833 patients treated with mAbs between January 2010 and December 2015 at a “third-level hospital” in Madrid, Spain, with a special focus on treatment modifications that were a direct result of AEs to mAbs. That focal study group had a population of 119 patients who either had an infusion reaction or a hypersensitivity reaction following treatment with their specific mAb.

There were 12 mAbs in the study group, 3 of which dominated the AE results: infliximab (61 AEs), rituximab (28 AEs), and adalimumab (12 AEs). The research team characterized the AEs by symptom, as cutaneous, respiratory, glottis edema, cardiovascular, neurological, gastrointestinal, lumbar pain, or fever. A majority of AEs were mild or moderate and responded to premedication with antihistamines, corticosteroids, or acetaminophen or a change in the mAb used for treatment, they noted. Six of the AEs required desensitization, “but all of the procedures were finally tolerated,” said Roa-Medellin.

Based on the results the authors concluded that mAbs cause a low incidence of AEs that require treatment modification. “The reactions represented only a tenth of the cases in which the treatment needed to be changed,” they explained, noting that anti-TNF α was the most-commonly involved MoAb in the reactions. “Premedication seems a good option for mild to moderate reactions,” Roa-Medellin said, and added that her team believes desensitization to be a good first option in the event of severe reactions “or when premedication is not successful.”

Note: Thirteen out of 48 desensitizations in the study had mild reactions of urticaria and/or pruritis. Only two had both, but both of those received infliximab. 