The Center for Biosimilars Staff

Biocon’s net profits for the past quarter 

 by 51%, according to a statement made by the Bangalore-based drug manufacturer.

Chairperson and managing director Kiran Mazumdar-Shaw explained the company’s disappointing financial results by saying that, while Biocon had a strong quarter for insulin sales, its financial performance was inhibited by a weak US dollar, the impact of goods and services taxes, and operational costs related to the company’s facility in Malaysia. News of the drug maker’s quarterly performance caused shares of the company to 

Biocon’s weak earnings are not the only bad news that the company faced in July; earlier this month, the French National Agency for Medicines and Health Products Safety (ANSM) found that Biocon had failed to comply with good manufacturing practices for 3 of its biosimilars made in the company’s facility in Bangalore, India. ANSM found 35 issues—11 of which were deemed “major deficiencies”&mdash;related to drug product manufacturing and quality control operations. Biocon 

 that it is working together with Mylan to implement a proposed corrective and preventative action plan with a goal of early ANSM re-inspection of its facilities.

Yet the company remains buoyed by several recent developments, most notably the FDA’s Oncologic Drugs Advisory Committee (ODAC)’s unanimous recommendation of approval for Biocon and Mylan’s trastuzumab biosimilar, one of the drugs affected by ANSM’s inspection results. The company also points to promising 

 from its insulin glargine biosimilar that it presented at the American Diabetes Association’s 77th Scientific Sessions.

“Much depends on regulatory approvals and tender outcomes for our biosimilars,” said Mazumdar-Shaw. “However, we will endeavor to maintain healthy core operating margins, going forward."

In order to gain a lucrative foothold in the US biologics marketplace, the company may need to look beyond approvals. Though many 

 ODAC’s recommendation of Biocon and Mylan’s trastuzumab for its potential to increase access to a lower-cost treatment option for HER2-positive metastatic breast cancer, questions remain as to whether the drug will gain acceptance and uptake in the US marketplace. A recent 

 by ZS Associates indicated that oncologists, payers, and pharmacy directors may be reluctant to prescribe or cover products manufactured by Biocon, and instead would prefer products manufactured by more established, well known drug makers.

Regulatory action for Biocon and Mylan’s trastuzumab biosimilar is expected in September.

Articles

Biocon’s net profits for the past quarter dropped by 51%, according to a statement made by the Bangalore-based drug manufacturer.

Eye on Pharma: Biocon's Profits Drop by 51% Despite Strong Insulin Sales

Biologic medications are an integral, crucial, and effective part of medical management for many life-threatening diseases and conditions, including cancer, but biosimilars are not without concerns. 

 about a recent position paper, published in 

outlining special concerns for oncologic biosimilars. 

Biologic medications are an integral, crucial, and effective part of medical management for many life-threatening diseases and conditions, including cancer, but biosimilars are not without concerns.

Infographic: Biosimilars in Oncology

 before the House Judiciary Committee this afternoon in a hearing titled “Antitrust Concerns and the FDA Approval Process.”  

Gottlieb opened his remarks by reiterating the FDA’s commitment to addressing the problem of high drug cost by encouraging competition, then itemized the steps the agency is taking to address barriers to competition in the pharmaceuticals marketplace:

Restricted distribution systems and access to drugs for bioequivalence testing.

 Gottlieb discussed the fact that risk evaluation and mitigation strategies (REMS) can be used by innovators to improperly withhold samples from generics developers, even in cases in which the FDA has informed a brand company in writing that it will not consider provision of a product to be a violation of REMS. He said that the agency has fielded—and forwarded to the Federal Trade Commission (FTC)&mdash;more than 150 inquiries from generics companies citing withholding of testing samples.

 For branded drug products approved with REMS with elements to assure safe use (ETASU), the FDA requires the generic applicant and originator to use a single, shared system to implement the ETASU before the generic’s application may be approved, though the agency may waive the requirement. Prolonged negotiation over the single, shared REMS requirement can be used to delay approval, Gottlieb noted, and can place a time and resource burden on the agency. While the agency hopes to pursue single, shared systems in most circumstances, it is “actively considering our authority and practices in this space,” he noted.

A vehicle for stakeholders external to the FDA to ask the agency to either take or refrain from taking an action, a citizen petition is commonly used to ask the agency not to approve a generic application. Gottlieb said that the resources the agency must devote to such petitions, many of which are ultimately dismissed as being without merit, are significant, and that the agency is considering ways to reduce the burden of these petitions.

A 1962 amendment to the Food, Drug, and Cosmetics Act required that all drugs must be shown to be effective—not just safe&mdash;prior to marketing. As a result, thousands of drugs required new efficacy evaluations to meet the legal requirement. Gottlieb estimated that more than 1000 prescription drug products have yet to be evaluated. The fact that these drugs have not yet been addressed under the agency’s 2006 Unapproved Drugs Initiative means that there is no clear pathway for generic versions to be approved.

 Dr Gottlieb described so-called “pay-for-delay” agreements as settlements in which drug companies resolve patent litigation over potentially infringing follow-on products by agreeing with generic makers to delay product entry in exchange for monetary benefit. He stopped short of saying that the controversial tactic inhibited competition, saying “we do not know when generic products would have entered the market if the patent litigation had continued and the companies had not settled with an agreement to delay marketing.”

Also testifying was Markus H. Meier, acting director of the FTC, who echoed Gottlieb’s concerns about REMS abuse, citizen petitions, and pay-for-delay arrangements. Yet, in comparison with Gottlieb’s measured approach to describing the difficulties facing the FDA, Meier took a bolder stance, saying “drug manufacturers have exploited certain features of the existing regulatory framework created by the Hatch-Waxman Act to extend exclusive rights well beyond the periods Congress provided to spur investments in innovation,” and calling REMS programs “an appropriate area for Congressional focus and concern.”

Meier echoed Gottlieb’s concerns about the use of REMS to delay generic entry, as well as refusal of testing samples to biosimilar and generics developers. Meier cited antitrust cases—including Celgene’s alleged use of REMS to prevent testing of its Thalomid and Revlimid, as well as Actelion’s alleged imposition of distribution restrictions to prevent competitors from accessing samples. Meier further indicated that the FTC has concerns about biosimilars manufacturers being denied information that would assist them in compliance with the Biologics Price Competition and Innovations Act (BPCIA).

Finally, Meier suggested that bipartisan House Bill 2212, the Creating and Restoring Equal Access to Equivalent Samples (

) Act, could reduce incentives to abuse regulation. The act would, he said, allow generics firms to initiate legal action against innovator companies and obtain samples for testing after establishing that they had complied with existing statutes. It would also provide a clearer path for generics firms to establish separate REMS programs if necessary.

Additional testimony in support of the CREATES Act was provided by David Olson, Esq, associate professor of law at Boston College Law School, who said that the legislation is a “narrowly tailored solution to the failure to share samples.” Alden Abbott, Esq, deputy director of The Heritage Foundation, testified that the act addresses current statutory limitations, as current “antitrust laws are ill-suited to combat anticompetitive regulatory manipulation.” Erika Lietzan, Esq, associate professor of law at University of Missouri School of Law, testified that she had concerns about the CREATES Act, citing “weak empirical support for any legislative action” and saying that the act is “flatly inconsistent with fundamental patent law principles,” while Aaron Kesselheim, MD, MPH, associate professor of medicine at Harvard Medical School, praised the act, but called for additional, more extensive reform.

FDA Commissioner, Scott Gottlieb, MD, testified before the House Judiciary Committee this afternoon in a hearing titled “Antitrust Concerns and the FDA Approval Process.”

FDA Commissioner Scott Gottlieb Testifies to Judiciary on Encouraging Pharma Competition

 prepared by the Analysis Group sought to describe the current pipeline of biopharmaceuticals under development that could benefit US-based patients within the next 5 to 10 years. 

Drawing on data from the Evaluate Pharma database—which curates publicly available information on companies and their products&mdash;as well as FDA data, the researchers identified new medicines under development or regulatory review as of August 2016, and found 6300 biopharmaceutical products (unique molecules) in global clinical development or under regulatory review that were a part of over 9500 projects (unique molecule-indication combinations). A range of projects explored novel scientific approaches in clinical development, including gene therapy, cell therapy, DNA and RNA therapy, and conjugated monoclonal antibodies (which use monoclonal antibodies joined to chemotherapy agents or other drugs to target specific cells, such as cancer cells). 

While the projects in question address a variety of therapeutic areas, the report shows a robust number of projects targeting the underserved population of diabetes patients—the report found a total of 749 projects and 432 products for the treatment of diabetes or diabetes-related complications:

•    3 projects filed with the FDA as of August 2016

Of the diabetes projects identified, 599 have the potential to result in the first products of a unique pharmacological class. A majority of the diabetes-focused projects seeking to be first-in-class are in preclinical research, with 16 projects in phase 3 trials. 

The report also identifies 11 projects and 10 unique products intended to treat diabetes or diabetes-related complications that are designated as orphan projects. However, the authors point out that its count of orphan-designated medicines under development may be low, as early-stage projects may not yet have orphan designation.

While the number of projects in the diabetes biopharmaceutical pipeline is promising, the authors remind their audience that, of the investigational compounds that eventually reach clinical trials, only 12% are ultimately approved by the FDA (after 10 to 15 years of testing and an average of $2.6 billion in development costs). Clinical trials have become increasingly complex in recent years, the authors note; compared with the period from 2001 to 2005, the period from 2011 to 2015 saw the mean number of total endpoints in a typical phase 3 trial protocol increase by 86%, and the total number of procedures (such as blood work and exams) conducted during such trials increase by 70%. The authors suggest that such a trend could lead to longer timeframes and increased costs for drug approvals unless efficiency measures can be properly implemented.

The authors conclude that, while it is impossible to accurately predict which projects and products under development will eventually reach patient populations, the current pipeline for biopharmaceuticals, including those intended to address the needs of patients with diabetes, is both extensive and innovative. While the need for continued development of new treatments for US patients remains high, the current pipeline, they say, “is laying the groundwork for tomorrow’s breakthrough therapies for patients with few other therapeutic alternatives.”

A recent report prepared by the Analysis Group sought to describe the current pipeline of biopharmaceuticals under development that could benefit US-based patients within the next 5 to 10 years. 

Biopharmaceutical Pipeline Includes 749 Projects Targeting Diabetes

The American College of Rheumatology (ACR) has issued a 

 to CMS’ 2018 Physician Fee Schedule (PFS) proposed 

The ACR, a professional membership organization that advocates for more than 9500 members that include rheumatology care providers and researchers, praised CMS for seeking stakeholder input on the ways in which the body can achieve transparency, flexibility, program simplification, and innovation with respect to its policies, including policies affecting payment for biosimilar products. ACR says that making improvements to Medicare will be essential to ensuring that rheumatology practices, especially practices that serve rural areas, can continue to provide quality care to patients.

The ACR voiced its support for a revision to the 

 (VM), an adjustment made on a per-claim basis to Medicare payments for items and services based upon physicians’ performance on quality and cost criteria. The proposed rule would reduce the VM adjustment:

From -4% to -2% for practices of 10 or more clinicians who do not meet CMS’ reporting requirements

From -2% to -1% for physicians practicing alone or in groups of up to 9 clinicians.

However, ACR calls on CMS to go further in easing the VM burden on practitioners by establishing a VM adjustment of 0% in 2018.

ACR also praised CMS for delaying the implementation of 

 (AUC) for advanced diagnostic imaging services. AUC, introduced in the 2016 PFS Final Rule, are evidence-based criteria that CMS says will “assist professionals who order and furnish applicable imaging services to make the most appropriate treatment decisions for a specific clinical condition” once they are implemented. The ACR says that it supports a gradual phase-in of AUC, and that it supports exemptions to the program for physicians practicing in underserved areas.

ACR also called on CMS to address what it sees as shortcomings to the proposed rule:

 ACR affirmed its belief that the process for receiving real-time feedback should be streamlined and simplified, and proposed that CMS offer user-friendly, quarterly Quality and Resource Use Reports along with 90 days for appeal.

 ACR indicated that cuts to reimbursement for injections could reduce patient access to key services.

. Emphasizing the failure of existing codes in reflecting the full range and complexity of the services that rheumatologists provide, ACR said that it hopes to see payment based on services provided rather than specialty designation.

. ACR voiced its support for the assignment of a unique J-code to each biosimilar product for better tracking and pharmacovigilance. CMS is 

 revising its current billing code policy, which groups payment for all biosimilar products referencing a single originator biologic by the same Healthcare Common Procedure Coding System (HCPCS) code. CMS reports in its proposed rule that it has received extensive feedback that the current policy could negatively impact not only pharmacovigilance practices but also price competition among biosimilars and biologics.

ACR reports that its full response to the proposed rule will be made during the public comment period. CMS is receiving 

 on the proposed rule through September 11, 2017.

The American College of Rheumatology has issued a response to CMS’ 2018 Physician Fee Schedule proposed rule, which was issued earlier this month.

The American College of Rheumatology Responds to CMS' Proposed Rule

 the US launch of its biosimilar infliximab, Renflexis, which it developed under a joint venture with Samsung Bioepis.

Merck’s product, a tumor necrosis factor (TNF) blocker referenced on Janssen Biotech’s Remicade, was approved by the FDA on April 21, 2017 for the treatment of Crohn’s disease, pediatric Crohn’s disease, ulcerative colitis, rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, and plaque psoriasis.

Merck will introduce the drug at a US list price of $753.39, which it says represents a 

 discount to the price of the reference Remicade. That price point puts renewed pressure on Janssen; while Remicade earned the Johnson and Johnson division $4.8 billion in 2016, or 

 of its 2016 revenue, Remicade’s sales slipped after competition from Celltrion's biosimilar infliximab, Inflectra. When Pfizer, which has commercialization rights to the drug, introduced Inflectra in 2016, it set its product’s list price at only a 

 discount to that of Remicade; Merck’s deeper discount has the potential to encroach on Remicade’s sales figures even further.

“Merck looks forward to launching Renflexis in the United States to help meet the needs of patients, physicians and payers,” said Dora Bibila, general manager of Merck Biosimilars. “As a global healthcare leader, Merck believes that biosimilars have the potential to help increase access to these important medicines while also providing savings for the health care system.” Merck plans to make available comprehensive education and support services for healthcare professionals, patients, and caregivers, including reimbursement and access support.

Despite Merck’s move to introduce Renflexis to the United States, Janssen seeks to retain its hold on the infliximab market through litigation. Earlier this year, Janssen filed a district court 

 to prevent the sale of Merck and Samsung Bioepis’ infliximab product in the US, saying that the biosimilar product’s manufacturers had violated several of its patents.

Samsung Bioepis, for its part, believes that the case will be resolved in its and Merck’s favor. “We are confident we do not infringe on Janssen’s patents,” a company spokesperson, 

 Reuters. “We will take all necessary measures against Janssen's attempts to violate patient rights and deny patient access to effective, lower-cost treatment options."

Merck today announced the US launch of its biosimilar infliximab, Renflexis, which it developed under a joint venture with Samsung Bioepis.

Merck Announces US Launch of Biosimilar Infliximab Renflexis

The Food and Drug Reauthorization Act of 2017, recently passed by the House, reauthorizes the Biosimilar User Fee Act (BsUFA). Learn 

 about changes to the BsUFA in its new iteration, BsUFA II. 

The Food and Drug Reauthorization Act of 2017, recently passed by the House, reauthorizes the Biosimilar User Fee Act (BsUFA). Learn about changes to the BsUFA in its new iteration, BsUFA II. 
 

Infographic: Changes to BsUFA Under FDARA

Hi, I’m Kelly Davio for the Center for Biosimilars, your resource for clinical, regulatory, business, and policy news in the rapidly changing world of biosimilars. Here are our top 5 biosimilars articles for the week of July 17:

most US-based health plans now cover at least 1 of the 2 available FDA-approved biosimilars

Number 4: A phase 3 trial of the proposed rituximab biosimilar candidate GP2013 shows 

positive results in patients with follicular lymphoma. 

Number 3: Molly Billstein Leber, manager of Medication Policy and Formulary Management for the Yale New Haven Health System, 

discusses the FDA’s Oncologic Drugs Advisory Committee’s unanimous recommendation of approval for biosimilars 

Number 2: At this week’s public meeting on the Hatch-Waxman Amendments, 

FDA Commissioner Dr Scott Gottlieb announced the upcoming publication of 2 documents related to the ANDA process.

And finally, Number 1: The FDA Reauthorization Act 

may proceed to a Senate vote sooner rather than later 

after the failure of the Better Care Reconciliation Act.   

Read these articles and more at centerforbiosimilars.com 

The Center for Biosimilars recaps the top 5 stories in biosimilars news for the week of July 17, 2017. 

The Top 5 Articles for the Week of July 17

Last week’s Oncologic Drugs Advisory Committee (ODAC) recommendation that the FDA approve 2 biosimilar treatments brought Swiss drug maker Roche a step closer to inevitable competition from biosimilar treatments.

ODAC voted unanimously to recommend the approval of Amgen’s biosimilar bevacizumab candidate ABP 215 (referenced on Roche’s Avastin) and MYL-1401O, Mylan and Biocon’s biosimilar trastuzumab candidate (referenced on Roche’s Herceptin). The drugs are widely expected to be approved by the FDA in September. 

While the slow pace of litigation surrounding biosimilar drugs in the United States suggests that Roche will not face an immediate threat to its US market share for bevacizumab and trastuzumab, Tim Race, analyst for Deutsche Bank, 

that "Roche has $22 billion of revenues exposed” to biosimilar products now making their way to the marketplace.  

 that it will be able to keep its sales dominance through the development of novel treatments, and some 

 suggest that the drug maker’s pertuzumab (Perjeta), a monoclonal antibody used in first-line therapy for HER2-positive metastatic breast cancer, in combination with trastuzumab and docetaxel, could help the company to do just that. Because pertuzumab would extend the duration of treatment, it would contribute to greater sales over time, and its joint use with trastuzumab could help to protect sales of Roche’s innovator Herceptin.

However, Roche’s recent setback with its immunotherapy treatment atezolizumab (Tecentriq) has raised concerns that the company’s innovative drugs may not be enough to retain its foothold in the oncology market. In April, atezolizumab was granted 

 approval as an initial treatment for patients with locally advanced or metastatic urothelial carcinoma. However, in May, the drug did not meet the primary endpoint of improving overall survival in the second-line setting in a phase 3 

 positive data from phase 1, 2, and 3 studies suggesting that the drug could be used in combination with other treatments across a range of other cancers, but the failure of the drug to perform in the treatment of bladder cancer came as a blow to Roche.

Other novel drugs in Roche’s pipeline are 2 drugs for the treatment of Alzheimer’s disease: crenezumab and gantenerumab. The drugs, both of which are in phase 3 development, could jointly reach $130 million in 

 by 2022 if approved. Also in Roche’s late-stage pipeline are lampalizumab, indicated to treat dry age-related macular degeneration; etrolizumab, indicated for ulcerative colitis and Crohn’s disease; and emicizumab, indicated in hemophilia A.

Last week’s Oncologic Drugs Advisory Committee recommendation that the FDA approve 2 biosimilar treatments brought Swiss drug maker Roche a step closer to inevitable competition from biosimilar treatments.

Facing Challenges From Biosimilars, Roche Hopes to Retain Dominance With New Products

The 2018 Medicare Physician Fee Schedule Proposed 

, issued by CMS on July 13, considers changing a contentious billing code policy affecting biosimilar products.

In its 2016 Physician Fee Schedule Final Rule, the body finalized a proposal that grouped payment for all biosimilar products referenced on a single originator product under common billing codes. However, in its Revisions to Payment Policies Under the Physician Fee Schedule and Other Revisions to Part B for Calendar Year 2018, due to be published in the Federal Register on July 21, CMS 

CMS states that it reviewed a number of comments on its Part B billing code policy, which revealed that many stakeholders opposed a single payment amount for biosimilars that rely on the same reference product. These commenters believed that such a regulation would decrease incentives for biosimilar makers to develop products, which could in turn lead to market consolidation and increased costs for biosimilar treatments. Others were concerned that prescribers’ choices could be limited by the grouping, while still others said that they believed that pharmacovigilance activities could be negatively impacted by the policy.

CMS reports that many commenters suggested that the body determine a payment amount for each biosimilar or biologic treatment using individual Healthcare Common Procedure Coding System (HCPCS) codes, and suggested that this approach could create a cost savings of 10% to 15% on biosimilars in comparison to their reference products.

However, some commenters supported CMS’s proposed regulation and their view of its effect on competition, saying that the potential market for biosimilars is less risky than that of innovator biologics, and believed that separate payment for each biosimilar could result in both reduced competition among manufacturers and also higher prices for Medicare beneficiaries. 

 that congressional Medicare advisors have recommended that CMS retain the policy, and that they have suggested that it could be used even more aggressively to group both reference and biosimilar products under the same codes.

Despite such support of the policy, CMS says that it “seeks to promote innovation, to provide more options to patients and physicians, and competition to drive prices down, recognizing that even though these two goals may be difficult to achieve concurrently, to delink them would be counterproductive.” CMS went on to say that “it is essential to take a measured approach that considers all options given the significant federal spending by Medicare on Part B drugs.” CMS says that it will seek comments regarding its payment policy as it continues to investigate alternatives to its current practice.

Biosimilars Forum hailed CMS’ decision to revisit the coding policy, saying that issuing unique HCPCS codes to each biosimilar product will help to ensure a robust and competitive marketplace for biosimilars, and that it could help spur innovation. “To ensure that the prescribed physician-administered biologics are given to patients, Medicare should allow a fair and predictable reimbursement to purchasers of biosimilars,” the nonprofit organization said in its July 14 statement.

CMS’ comment period on the entirety of its proposed rule will remain 

The 2018 Medicare Physician Fee Schedule Proposed Rule, issued by CMS on July 13, considers changing a contentious billing code policy affecting biosimilar products.