Jackie Syrop

Several biopharmaceutical companies are seeking further clarification from the FDA on the draft biosimilar 

 the agency released in January 2017. The draft, which called on companies to use “switching studies” to determine the safety and efficacy of a biosimilar with respect to its reference product, has a 

The draft FDA guidance says that the comparator product, rather than only being used as a control, should be used in both the active switching arm and the control non-switching arm of switching studies, and notes that using a non-US-licensed comparator product generally would not be appropriate. The guidance also says there is no single data package that will work for all proposed interchangeable products.

In their comments, biopharmaceutical companies and the Biosimilars Forum took issue with the definition of interchangeability in the guidance and the confusion surrounding the terminology used to describe physician-mediated switching and pharmacy-level substitution.

Pfizer noted that interchangeability is defined to mean that the biological product may be substituted for the reference product without prescriber intervention. “It is a prerequisite for substitution at the pharmacy level based on a growing body of state laws,” the company countered. Pfizer urged the FDA to address the confusion related to physician-mediated switching and pharmacy-level substitution to ensure the appropriate use of terminology so it is clear that physician-mediated switching is part of usual medical practice and does not require an interchangeability designation. The company also disagreed with the FDA’s use of the phrase “fingerprint-like characterization” because it lacks a clear definition, creates uncertainty for sponsors developing proposed interchangeable biologics, and can be manipulated to undermine confidence in biosimilars.

Pfizer also disagreed with the draft guidance’s recommendation that US sponsors use US-licensed reference product in a switching study, saying the recommendation has the potential to create practical challenges regarding where the study can be conducted. The Biosimilars Forum believes this aspect of the guidance could undermine the global nature of biosimilar development.

Pfizer and Genentech were concerned with the guidance’s discussion of labeling and naming of biosimilars. It would not be advisable for an interchangeable product to carry the same suffix as designated in the proper name of the reference product, Pfizer said, and recommended that labeling of biosimilar and interchangeable biological products include an interchangeability statement that identifies whether or not interchangeability has been evaluated and outlines what is meant by interchangeability.

Boehringer Ingelheim said in its comments that the guidance’s use of the terms “totality of the data” and “residual uncertainty” were arbitrarily defined and burdensome. “More importantly,” the company wrote, “an approved biosimilar product will have already met the criteria for biosimilarity, including an assessment by FDA that it is ‘highly similar’  to the reference product, and is not of inferior quality to any biosimilar product that is also interchangeable.” It is critical to the designation of interchangeability, the company continued, that it not be misinterpreted as designating a superior or higher-quality product to an approved biosimilar that is not interchangeable.

Novartis/Sandoz’s comments focused on post-market changes to biosimilars, noting that if sponsors provide comprehensive data and the FDA carefully reviewed and approved post-approval changes, there should be no expectation that a change in safety or efficacy profile will occur, and accordingly, it is not necessary to re-establish either biosimilarity or interchangeability once it is initially established with a comprehensive and convincing data package.

Expressing strong support to the FDA’s proposal to require robust switching studies, the president of the American College of Rheumatology (ACR), Sharad Lakhanpal, MBBS, MD, said in a 

. “Such studies are vital to achieve a clear understanding of what patients are likely to experience with changing formularies in a multi payer, multi state, and ever changing market.” He further emphasized the need for open access to data from these switching studies, for both physicians and outside investigators.

“While the ACR does not support automatic extrapolation, we do believe that extrapolation should be rigorously studied and fully utilized to help reduce the cost of these drugs,” he added. Additionally, ACR supports the use of distinct suffixes for each biosimilar and believes the choice of treatment should be left to the physician and patient. To that effect, Lakhanpal urged the FDA to ensure product labels clearly state interchangeability with the reference product.

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Biopharma Companies Seek Greater Clarification About FDA's Interchangeability Guidance

 to HHS Secretary Tom Price and CMS administrator Seema Verma, MPH, expressing their concerns with the biosimilar reimbursement policy in CMS’ 2016 Medicare Physician Fee Schedule proposed rule, which states that each follow-on biologic, or biosimilar, associated with the same reference product will be reimbursed at a single payment rate based on their average sales price under Medicare Part B, which was established on October 30, 2015.

Biosimilars Forum president Stacie Phan said the action was needed more than ever now that the FDA has 

 for the same reference product, infliximab—following CT-P13 (Inflectra), infliximab-abda (Renflexis) was just recently approved. “Unless action is taken now, this will be a critically missed opportunity to help so many who are facing serious diseases and disorders and who could benefit from biosimilars,” Phan said. The Biosimilars Forum is a nonprofit organization whose mission is to advance biosimilars in the United States with the intent of expanding access and availability of biologic medicines.

The letters that the members of Congress wrote to 

 urge the officials to correct the current policy to reflect the biosimilar payment and coding requirements of the Biologics Price Competition and Innovation Act of 2009. The letters urged the reversal of current reimbursement policy, and requested that the policy instead employ a separate billing code and reimbursement rate so each biosimilar gets its own unique Healthcare Common Procedure Coding System code, commonly called the HCPCS code.

The letters stress that biologics are complex molecules and any reimbursement structure must appropriately reflect the complexity of these products and the differences between individual biosimilars. These differences are acknowledged by the statutory provisions establishing the biosimilar approval pathway, the letter to Secretary Price notes.

The members of Congress said that patients and physicians, pharmacy groups, biosimilar makers, and stakeholders that appropriate reimbursement for biosimilars have all expressed concerns about the rule, which does not appropriately reflect the complexity of the biosimilar products or the differences between individual biosimilars. “Biosimilar drugs hold enormous promise for improving health care outcomes for patients and reducing costs for both patients and health care payers such as Medicare and Medicaid,” the letter to Ms Verma states. “The emergence of biosimilar drugs has the potential to revolutionize the treatment landscape for many patients by offering them more treatment options at lower cost.” A more market-based policy will better support innovation, access, and affordability of these medications, the letter notes.

US Congressional Delegation Expresses Concern Over Biosimilar Reimbursement Policy

 positive top-line data from the second clinical trial of its lead development candidate B12019, a biosimilar of Amgen’s pegfilgrastim (Neulasta) to treat chemotherapy-induced neutropenia. The company announced that the randomized, double-blind, 3-period crossover study demonstrated that B12019 was comparable to its reference product with respect to pharmacodynamics (PD) and immunogenicity.

The study, conducted in 96 healthy volunteers in Germany, was based on specific advice from the European Medicines Agency (EMA), and was tailored to the specific properties of pegfilgrastim. The primary end points, area under the effect curve for PD, and anti-drug antibody rate (ADA) for immunogenicity, confirmed comparability to the originator product. All secondary end points were achieved and B12019’s safety profile was found comparable to the reference pegfilgrastim, the company said. Further trial data are to be presented at upcoming scientific meetings.

Headquartered in Pamplona, Spain, Cinfa Biotech, expects to make a Marketing Authorization Application (MAA) submission for B12019 with the EMA in the second half of 2017. Ruediger Jankowsky, PhD, managing director of Cinfa Biotech, said these positive results from the company’s second study confirm the biosimilarity of B12019 and the reference pegfilgrastim, which were also demonstrated in the first trial. “Both studies, together with the analytical and functional comparability data, support the high quality of our product candidate,” said Jankowsky. 

Several biosimilar developers have tried to obtain approval for proposed biosimilar versions of pegfilgrastim, a long-acting version of filgrastim (Neupogen), also manufactured by Amgen, but have 

 in both the US and Europe. Biosimilars of Neupogen have been on the market for years in Europe, and Sandoz’s biosimilar of Neupogen, Zarxio, was the first a biosimilar approved in the United States and was 

 in 2015. But Neulasta is a bigger, more complex biologic, and biosimilar makers have not yet had a pegfilgrastim biosimilar approved by the EMA or the FDA.

In the United States, 2 manufacturers of candidate pegfilgrastim biosimilars are being sued by Amgen: the company 

 a legal action in California state court against biosimilar maker Coherus in March 2017 alleging that Coherus had engaged in a “massive conspiracy” to steal Amgen’s trade secrets for Neulasta. Claiming the lawsuit is without merit, Coherus said it is an effort by Amgen to delay competition in the pegfilgrastim market. Coherus’ biosimilar to pegfilgrastim (CHS-1701) is scheduled for a June 9, 2017, regulatory hearing at FDA.

In a separate legal action, Amgen filed a 

 against Canadian biosimilar maker Apotex, seeking to prevent the company from giving Amgen the required 180-day notice of marketing of its proposed pegfilgrastim biosimilar until after Apotex gets FDA approval, which has not yet occurred. (Apotex’s pegfilgrastim biosimilar candidate was accepted for FDA review in December 2014.) Amgen’s position on notice was upheld by the US District Court as well as the Federal Circuit Court on appeal. The US District Court did hold that Apotex had not  infringed on patents that Amgen had challenged; that decision is being appealed by Amgen. The US Supreme court denied Apotex’s request for review of the District Court decision.

There is another potential pegfilgrastim candidate in the pipeline. In February 2017, the FDA 

 Mylan/Biocon’s proposed pegfilgrastim biosimilar (MYL-1401H) for review. The FDA’s goal for a decision on the application, based on the User Fee Act, is October 9, 2017.

Yet Another Pegfilgrastim Biosimilar Candidate Announces Positive Clinical Study Data 

 FDA Commissioner Scott Gottlieb, MD, said the agency would build on past progress and mission to address 21st-century challenges including  the opioid crisis, rising drug prices, and modernization of how the agency works. He discussed the importance of ensuring that drugs, including complex biologic drugs, are affordable and accessible, and said it was important that the generic drug process isn’t being inappropriately gamed to delay competition and disadvantage consumers.

 that the FDA’s greatest immediate challenge is the problem of opioid abuse, a public health crisis of staggering human and economic proportion, and not one the FDA can solve alone. But the FDA has an important role to play in reducing the rate of new abuse and in giving healthcare providers tools to reduce exposure to opioids to only clearly appropriate patients. In the coming weeks, the Commissioner said, he would have more to say on how the agency will take even more forceful steps to address the crisis.

The agency needs to be patient-centric and science-based in all that it does, Gottlieb told staff, and said the FDA must make sure that it maintains the gold standard for regulatory science and independent, science-led decision making in all its efforts. “Looking ahead, we sit at a time of great promise,” Gottlieb said. “Among some of the reasons I’m so optimistic about our shared future are new scientific opportunities, like gene therapy and regenerative medicine that give us plausible hope that we might be able to actually cure many more diseases.”

Gottlieb noted that scientific advances provide better tools for the agency’s regulatory work, and emphasized the need for the FDA to modernize how it works to be able to meet evolving challenges. He believes that modernizing the regulatory process and making it more efficient can improve consumer protection and promote health.

To that end, Gottlieb said there is an opportunity to greatly improve FDA’s public health protection role through the Program Alignment being undertaken by the Office of Regulatory Affairs. “We look forward to achieving operational efficiencies that can improve our ability to fulfill our public health mission and protect consumers” to safeguard food and cosmetics, improve nutrition, and protect consumers and livestock from the emerging threat of antimicrobial resistance. He also emphasized the need to reduce the rate of smoking and protecting children from the dangers of tobacco use.

Of the several challenges facing the FDA, Gottlieb placed drug pricing at the top. “Too many consumers are priced out of the medicines they need,” he said. Although the FDA doesn’t play a direct role in drug pricing, the agency still needs to take meaningful steps to get more low-cost alternatives to market to increase competition and give consumers more options. “This is especially true when it comes to complex drugs and biosimilars,” he said. He noted that he planned to address the topic of biosimilars and generics in the coming weeks.

Gottlieb also discussed a mandate to be forward-leaning when it comes to evaluating safety and efficacy in view of emerging scientific insight and better analytical tools. He said that implementing the 21st Century Cures Act is a key priority and that steps must be taken to foster innovation and regulate areas of promising new technologies in ways that don’t raise costs of development or reduce innovation. “We must do all of these things without compromising our primary mandate to protect the public health.”

New FDA Commissioner Will Prioritize Opioid Crisis, Drug Pricing 

A Danish study reports that switching from the originator drug infliximab (Remicade) to biosimilar CT-P13 (Inflectra/Remsima) does not appear to have had a negative effect on inflammatory arthritis disease activity in over 800 patients after 1 year of follow up. The study was published in the May 4, 2017 issue of 

 at the Digestive Disease Week 2017 in Chicago last week.

The switch from Remicade to Inflectra was initiated by a Danish national guideline that all patients treated with infliximab should switch to the biosimilar for economic (not medical) reasons by May 2015. Patients and physicians had no say in the matter. In January 2017, the FDA issued a draft guidance about biosimilar interchangeability that recommended these kinds of switching studies be done to address safety and efficacy concerns around biosimilars.

The patients had rheumatoid arthritis (RA), psoriatic arthritis (PsA), and axial spondyloarthritis (AxSpA) and were enrolled in the DANBIO rheumatic disease registry. Disease activities 3 months before and after the medication switch and changes over time were calculated.

A total of 802 patients (403 RA, 120 PsA, and 279 AxSpA; 51% women; median age 55) were switched from Remicade to Inflectra. The average treatment duration with the originator drug, prior to the switch to the biosimilar, was 6.8 years (range, 4.3 to 9.5 years). Follow up was 413 days, during which 16% stopped taking the biosimilar, mostly because of lack of effect or adverse events.

Bente Glintborg, MD, of the Rigshospitalet in Glostrup, and colleagues 

 that disease activities were similar 3 months before and following the switch from Remicade to the biosimilar infliximab. The absolute retention rates were 83.4% for the biosimilar and 86.8% for Remicade (

 = .03), an absolute difference of 3.4%. Flare rate, defined as a change in 28 Joint Disease Activity Score greater than or equal to 1.2 (RA/PsA) or Ankylosing Spondylitis Disease Activity Score greater than or equal to 1.3, were also similar.

 “To our knowledge, this is the first study of large-scale, nonmedical switching in routine care with prospective data collection,” the authors write. The availability of historic DANBIO disease registry data allowed the researchers to use the patients as their own controls with respect to fluctuations in disease activity before and after the switch, and to identify a historic infliximab cohort for comparison of retention rates. Patients whose previous infliximab treatment was longer than 5 years had a greater biosimilar retention rate. Retention rates for the biosimilar across diagnoses were comparable, though slightly lower for RA patients.

The study authors noted that the difference between 1-year retention rates for the biosimilar could be slightly lower than the originator drug because of a so-called “nocebo effect,” that is, negative expectations toward the drug or residual confounding.

The study was funded in part by a research grant from AbbVie.

Switch from Remicade to Inflectra Did Not Affect Efficacy, Per Danish Study

In its latest report on the impact of biosimilar competition on price, volume, and market share, the European Commission 

 a consistent average price reduction in therapeutic areas that have seen biosimilar competition. The report, prepared by QuintilesIMS in cooperation with industry stakeholders, used 2016 data and looked at 6 established therapeutic areas in which there is biosimilar competition: epoetin (EPO), granulocyte colony-stimulating factor (G-CSF), anti-tumor necrosis factor (anti-TNF), fertility/gonadotropin (hGH) preparations, and recombinant human insulins. The report was presented in Brussels at the European Commission’s stakeholder conference on May 5, 2017.

The following are 4 key takeaways from the report:

1. Biosimilars reduced the average list prices for the whole product class in European countries.

 Biosimilar entry can have almost as large an impact on the total market price as it has on the    biosimilar/reference product price, the report states, citing the example of Portugal, where the price of EPO fell 66% in the year after the biosimilar entered the market.

The correlation between biosimilar market share of the total market and price reduction of the total market is weak. The report found that high savings can be achieved even if the biosimilar market share is low. “Price reduction can be achieved through price regulation interventions and/or commercial decisions of manufacturers,” the report notes. Even if the biosimilar is not, in the end, the product sold, it is likely an essential step to generate a more competitive environment, which leads to lower prices. The report cautions, however, that in the long term, low biosimilar uptake could lead to fewer new biosimilars being developed, reducing the overall competitive pressure.

Drug classes with more than 1 biosimilar display a weak correlation between the number of biosimilar competitors and the price change within the entire market. While savings can be achieved without competition from multiple biosimilars, in the long term, it may be necessary to have multiple biosimilars to achieve the full effect of competition, the report suggests.

Lower reference product pricing lowered biosimilar market penetration. 

The larger the price cut on the reference product, the lower was the impact of biosimilars. This was observed for at least 2 therapy classes: anti-TNF and hGH. “This illustrates that originator competitive pricing strategies can influence the uptake of biosimilars in some areas,” the report states. However, reducing originator prices could result in biosimilars not entering the market at all, restricting competition. 

In therapeutic classes with multiple biosimilar competitors, the first biosimilar to market typically has the highest biosimilar market share.

 Therefore, time to market for biosimilars can impact uptake in the class. The report found that where multiple launches occurred in the same month in a country, market shares for these products were assigned to the same rank. 

Biosimilar competition increased consumption of drug products across several therapeutic areas. 

This was true even if there was already high usage of that therapy class. For example, in Sweden, there was a significant increase in consumption of anti-TNFs after a biosimilar became available—even though there was already high usage of that class of drugs. Thus, the report concludes, biosimilar competition increased patient access to the product class. Lower prices increase patient access, the report notes. However, other factors can affect usage, including:

New indications or restrictions of indications (such as EPO safety warnings)

General economic conditions imposing use restrictions

Changes in diagnosis and prevalence of diseases.

Overall, biosimilar competition contributes to increased patient access of the whole market. Although the total market volume uptake varies significantly by class in Europe, it must be noted that all products in these therapeutic areas, including biosimilars, have led to varying degrees of increased patient access in each country.

While there is not just one formula that will work to achieve savings potential, we can learn from the experience in all countries, the report states.  

Biosimilar Competition Has Led to Consistent Price Reduction in Europe 

The recently approved biologic drug dupilumab (Dupixent), Regeneron/Sanofi’s treatment for atopic dermatitis (eczema), is getting a 

 from payers despite its $37,000 annual price tag.

 on March 28, 2017, for the treatment of adults with moderate to severe atopic dermatitis that cannot be controlled by topical treatments. Regeneron/Sanofi has asserted that the twice-monthly subcutaneous injection will deliver value and improve health outcomes for patients with few options. According to analysts, initial responses from pharmacy benefit managers (PBMs) suggest potentially strong uptake of the new drug because it fills an unmet need. 

Atopic dermatitis, which causes severe itching, pain, visible skin lesions, sleep disturbances, and mental health effects, is 

 in 5%-20% of children worldwide and approximately 11% of children and an estimated 3%-7% of adults in the United States. Current therapies for atopic dermatitis include nonpharmacologic interventions such as moisturizers, bathing and wet wraps, and topical drug treatments such as corticosteroids, calcineurin inhibitors, and phototherapy. These require up to an hour of skin care per day. Systemic treatments include immunosuppressants such as methotrexate, cyclosporine, and azathioprine—none of which are FDA approved for eczema.

Clinical trials that evaluated dupilumab 

 that it is at least as effective as cyclosporine and more effective than phototherapy in controlling atopic dermatitis. Approximately 70% of patients who took the drug every week or every 2 weeks saw improvement in their skin disorder, and approximately 37% of patients showed clearing or near-clearing of skin lesions. With respect to safety, dupilumab may be safer than cyclosporine, which carries a possible risk of infections, cancer, and phototherapy, which can cause burns, premature skin aging, and skin cancer.

 that 2500 prescriptions for dupilumab have been written by 1200 physicians in the first month itself since the product was launched. IMS suggests 200 prescriptions were filled in the fourth week following product launch, promising rates which compare favorably with other successful recent drug launches, such as the psoriasis drug Otezla.

 In its recent draft report, the Institute for Clinical and Economic Review (ICER) 

 that most topical corticosteroids were covered by private carriers with preferred drug status. ICER reported variable coverage of topical calcineurin inhibitors tacrolimus (Protopic) and pimecrolimus (Elidel); for more severe disease, cyclosporine was often covered as a preferred agent with no requirements for step therapy or prior authorization. Targeted phototherapy was covered by all plans when patients didn’t respond to any topical treatments. ICER further reported that since most patients with atopic dermatitis who are candidates for systemic therapy don’t receive it, dupilumab will likely be used in patients who have not been offered other systemic therapies.

Importantly, ICER concluded that at a net price of $30,000 per patient per year for dupilumab, the cost per additional Quality Adjusted Life Year (QALY) was approximately $97,600. For patients with severe atopic dermatitis, the cost per QALY was $75,100 and for those with moderate disease the cost was $125,500.

 that the cost per QALY was below the usually accepted willingness-to-pay threshold of $150,000 per QALY, so that regardless of price, ICER found that dupilumab would be more likely to improve health outcomes compared with usual and existing care, but would do so with additional cost. At a net cost of $16,000 per patient per year, Porges says, he assumes rapid adoption in severe atopic dermatitis and significant adoption in moderate disease.

Initial responses from pharmacy benefit managers are positive. Express Scripts has included dupilumab on its National Preferred Formulary. Spokesperson Jennifer Luddy 

 that there are other, less effective treatments that cost more than Dupixent, and there are treatments that cost much less but may not help patients with the most severe form of atopic dermatitis. She praised Regeneron/Sanofi’s work to engage payers early and get their input. “Regeneron and Sanofi did reach out early, and we had a good amount of education on both sides about the product and about the need to ensure appropriate access for patients.” Prime Therapeutics LLC is negotiating with Sanofi/Regeneron to finalize formulary strategy, reviewing clinical data for Dupixent and evaluating safety and efficacy and determining formulary position.

Regeneron/Sanofi will seek an indication for dupilumab for patients younger than age 12, and a phase 3 study for that began this quarter.

Strong Early Launch for New Eczema Drug Dupilumab, Despite Price

Three studies presented at Digestive Disease Week (DDW) 2017 in Chicago suggest the possibility that the infliximab biosimilar, Inflectra, can be used interchangeably with the reference drug Remicade. Two of the trials 

 in patients switching from Remicade to the biosimilar version, and all 3 showed no significant differences in any efficacy and safety endpoints. These included clinical and biomarker effects, pharmacokinetics, adverse events, and development of anti-drug antibodies. The trials involved different patient populations.

None of the biosimilars currently approved in the United States have been designated as interchangeable with the reference agents. In order to demonstrate interchangeability, the FDA requires drug sponsors to present data from so-called switching studies. While none of the 3 studies presented at DDW 2017 were switching studies, they evaluated patients stabilized on Remicade who then switched to Inflectra, which was 

, described by Young Ho Kim of Sungkyunkwan University School of Medicine in Seoul, South Korea, was a phase 3 study of 214 patients new to infliximab, randomized to either the reference drug or the biosimilar. The primary endpoint was a 70% reduction on the Crohn’s Disease Activity Index at 6 weeks (although blinded treatment and assessments will continue to week 30). Researchers noted no differences on primary endpoint or dozens of secondary endpoints, including achievement of remission, freedom from supplemental steroids, and levels of anti-drug antibodies through week 30. Rates of adverse events were similar.

The second and third studies followed patients who switched from Remicade to the Inflectra. The first of these, reported by Kristin K. Joergensen of Akershus University Hospital in Loerenskog, Norway, presented results from the year-long 

 conducted in 24 centers across Norway. The 

 enrolled 482 patients who had any of the approved indications for Remicade: Crohn’s disease, ulcerative colitis, spondyloarthritis, rheumatoid arthritis, psoriasis, and psoriatic arthritis.

The primary endpoint, assessed at week 52, was the proportion of patients showing significant clinical worsening on the relevant scores for each condition. Patients in the study had been on infliximab for at least 3 years (mean, 7 years). There were no significant differences in any measure, meeting pre-specified criteria for non-inferiority of biosimilar infliximab versus the original drug. There did appear to be a significantly higher rate of clinical worsening at week 52 for Inflectra compared with Remicade (36.5% vs 21.2%), but rates of clinical remission were similar. The trial was not powered to test non-inferiority for individual conditions, and there was no difference in the rates of anti-drug antibodies.

—a small, open-label trial, presented by Anne Samira Strik of the Academic Medical Center in Amsterdam&mdash;mainly reported on pharmacokinetic and biomarker endpoints. The study was conducted in 61 patients who had been stable on doses of Remicade, with Harvey-Bradshaw index scores of no more than 4 points. The primary endpoint was a change from baseline in trough drug concentration in each patient, comparing the level of Remicade just before receiving the first dose of Inflectra with the level of biosimilar after 8 and 16 weeks. The  biosimilar demonstrated non-inferiority with Remicade. There were no differences in adverse events, and rates of anti-drug antibodies did not change after the switch.

 the strength of the studies’ findings on anti-drug antibodies. They pointed out that the studies only addressed a 1-way switch from Remicade to Inflectra and thus it is not known what the immunogenicity will be with multiple switching. Some were concerned that the patient populations in the studies were “selected”—for example, if patients had longer experience with infliximab, those prone to developing anti-drug antibodies wouldn’t be enrolled because they would have already developed the antibodies and would have been taken off the drug. Thus, they said, it could not be ruled out that clinically significant neutralizing antibodies could develop in real-world patients. Joergensen agreed that additional studies are needed to investigate multidirectional switching.

Celltrion, sponsor of the biosimilar infliximab, funded Kim’s study, and some of his coauthors were employees of Celltrion. Joergensen disclosed no relevant relationships with industry. Strik’s study was funded by Mundipharma International,  and some coauthors were company employees.

Three Studies at DDW 2017 Suggest Infliximab Biosimilar Getting Closer to Interchangeability

The White House meeting on May 8, 2017, between top Trump administration officials and biotech executives, university leaders, academic healthcare leaders, and the head of the National Institutes of Health (NIH) did not include a discussion of drug pricing even though the issue was expected to be raised by administration officials.

, organized to discuss the importance of basic biomedical research to improving human health and fueling economic growth, included executives from Celgene, Regeneron, and Vertex. The original agenda described the meeting as a chance for “private sector and thought leaders to describe their institution and its connection to federal funding,” after the Trump administration proposed cutting $1.23 billion from the NIH budget in fiscal 2017 and $5.8 billion next year—about an 18% reduction.

Most of the cuts would have come from research grants. Trump said in the early days of his administration that the drug industry is “getting away with murder” because of the prices it charges for drugs.

The meeting’s main event was attended by Ivanka Trump, Jared Kushner, HHS Secretary Tom Price, and, for a period of time, Vice President Mike Pence. President Trump did not attend the 2-hour meeting, but invited participants to the Oval Office following it.

 The topic of drug pricing did not appear to have been discussed, according to NIH director Francis Collins. “There’s all kinds of elephants, and the room is crowded with them, I suppose, but that one didn’t get much attention,” he 

 in a post-meeting interview. The main focus of the meeting was the case for support of biomedicine in America, Collins said, how all the parts fit together in order for discoveries, advances, and disease cures to continue to happen at an accelerated pace.

Collins reported that 1 meeting attendee said that for the first time her postdoctoral fellows from China, who were training in the United States, were declining to stay in the country after they finished, instead of returning to China. “This can’t be a good thing for our future if we’re trying to build a future that’s based upon talent,” Collins said. “A lot of the talent that we take for granted no longer comes so easily or stays once they’ve been trained.” In addition to reports of a negative impact on biomedical startups and research as a result of the proposed research cuts, Collins said that young scientists are having a hard time funding their work. “We know we’re not funding a lot of good science and we’re discouraging some young investigators who ultimately may decide to give up,” he concluded.

The biotech CEOs also focused on the case for government funding of basic scientific research, each  stating unequivocally that they count on the NIH to fund basic science as their shareholders would never allow the companies to fund that type of science. The industry leaders focused on the need to ensure that US dominance in biomedical research continues, and discussed scientific opportunities including research in Alzheimer’s, Parkinson’s schizophrenia, and traumatic brain injury.

Drug Pricing Not Discussed at White House Meeting of Biotech Execs and NIH 

 that it will launch a pilot project later in 2017 for prequalifying biosimilars of cancer medications. The organization noted that it was a step towards making some of the most expensive biotherapeutic cancer treatments more accessible to low- and middle-income countries.

The Prequalification of Medicines Programme (PQP) is a 

 provided by WHO to assess the quality, safety, and efficacy of medicinal products. Prequalification ensures that medicines supplied by international procurement agencies meet acceptable standards of quality, safety, and efficacy, and gives the procurement agencies working to distribute drugs in resource-limited countries the choice of a wide range of quality medicines for bulk purchase. If the drugs meet international standards, they are listed on the WHO website as eligible for procurement, giving purchasing agencies a range of quality-assured medicines, vaccines, and diagnostics from which to choose. Many low-income countries use WHO’s list of prequalified products to guide their selection of medicines, vaccines, and technologies for national procurement, according to WHO, and it may also contribute to an increase in competition and further reduce the price of medicines.

In September 2017, WHO will invite manufacturers to submit applications for prequalification of biosimilar versions of 2 products on the WHO Essential Medicines List: rituximab (Genentech’s Rituxan, used principally to treat Non-Hodgkin’s lymphoma and chronic lymphocytic leukemia) and trastuzumab (Roche’s Herceptin, used to treat breast cancer and stomach cancers). WHO is also studying options to prequalify insulin.

Once PQP invites manufacturers, they are asked to provide a comprehensive set of data about the quality, safety, and efficacy of the product being evaluated, including purity, stability, and clinical trial data. A team of assessors, including WHO staff and experts from global regulatory authorities, evaluates the presented data. Inspectors verify that manufacturing sites comply with WHO good manufacturing practices and verify that at any contract research organization that conducted trials related to the product also comply with WHO good clinical and laboratory practices. The PQP process can take from 3 months onward depending upon the quality of the data and completeness of the manufacturer’s records.

“Innovator biotherapeutic products are often too expensive for many countries, so biosimilars are a good opportunity to expand access and support countries to regulate and use these medicines,” noted Marie-Paule Kieny, MD, WHO assistant director general for health systems and innovation. If WHO finds that the biosimilars submitted for prequalification are comparable to the originator products in terms of quality, safety, and efficacy, the organization will list those medicines, which will become eligible for procurement by United Nations agencies.

Suzanne Hill, B. Med (Hons), Grad Dip Epi, PhD, FAFPHM, WHO’s director of essential medicines and health products, said biosimilars could be game-changers for access to medicines for certain complex conditions, but they need to be appropriately regulated to ensure therapeutic value and patient safety. She noted that increased use of biosimilars will require patients and prescribers to understand and trust that the benefits of biosimilars substantially outweigh any risk. WHO will be looking to countries with positive experiences with biosimilars, and partner for support in educating prescribers and patients on their benefits.