The Center for Biosimilars Staff

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 the top 5 biosimilars articles for the week of September 11.

Number 5: Poster presentations at last week’s European Society for Medical Oncology conference included the results of 

5 studies on biosimilar trastuzumab candidates

the FDA has accepted its Biologics License Application for a proposed rituximab biosimilar

Number 3: During a panel at the 2017 AAM Biosimilars Council Conference, 

regulatory leaders from Pfizer and Sandoz shared their experiences

 with the development of their biosimilar products.

Number 2: Dr Kashyap Patel, managing partner at Carolina Blood and Cancer Care, 

addresses challenges surrounding biosimilars in the US marketplace

the FDA approved ABP 215, the first bevacizumab biosimilar

Finally, last week, our newsletter asked you how important it is to educate patients about biosimilar treatments. To view results of the poll, visit 

To read all of these articles and more, visit centerforbiosimilars.com.

Articles

The Center for Biosimilars recaps the top 5 stories in biosimilars news for the week of September 11. 

The Top 5 Biosimilars Articles for the Week of September 11

 of Amgen’s bevacizumab biosimilar, ABP 215 (Mvasi). It is the first FDA-approved biosimilar of Avastin, which is approved in the United States and European Union for the treatment of patients with unresectable, locally advanced, recurrent, or metastatic non-squamous non—small cell lung cancer (NSCLC), metastatic carcinoma of the colon or rectum, and metastatic renal cell carcinoma.

The biosimilar’s approval was based on a comprehensive data package including analytical, pharmacokinetic, and clinical data that demonstrated that Mvasi and the reference Avastin are highly similar, with no clinically meaningful differences in terms of efficacy, safety, and immunogenicity between the drugs. Clinical data 

 in Amgen’s Biologics License Application include results from a phase 3 study in patients with NSCLC, which met its primary endpoint of showing clinical equivalence to Avastin.

Sean E. Harper, MD, executive vice president of research and development at Amgen, 

 that “The approval of Mvasi marks a significant milestone for healthcare practitioners and patients as the first anti-cancer biosimilar approved in the United States.” According to David Nicholson, chief research and development officer at Allergan, Amgen's partner in developing the drug, the approval “underscores our joint commitment to bring cancer biosimilars to market to help patients.” 

FDA Commissioner Scott Gottlieb, MD, said that “Bringing new biosimilars to patients, especially for diseases where the cost of existing treatments can be high, is an important way to help spur competition that can lower healthcare costs and increase access to important therapies.”

Kashyap Patel, MD, medical oncologist at Carolina Blood and Cancer Care, hailed news of the drug's approval, saying, "As a community oncologist, I welcome any additional tool that would provide us an option at a possibly competitive price. The approval of the bevacizumab biosimilar will likely increase access to anti-VEGF [vascular endothelial growth factor] in treatment of approved indications, especially in underinsured patients or patients with very high co-pays...ABP 215 will reduce the cost of treatment for advanced lung cancer, colon cancer, glioblastomas, and ovarian cancer. Oncology practices participating in alternative payment models such as OCM [Oncology Care Model] or third-generation ACOs [accountable care organizations] are more likely to adopt quickly as they are responsible for the overall cost of care and any improvement in overall cost would be an extremely welcome step."

In July, the Oncologic Drugs Advisory Committee voted unanimously in favor of ABP 215’s approval, despite some of the voting members having expressed 

 about the homogeneity of the patient population studied in the clinical trials, and noted that the patients were primarily white and exclusively male.

Amgen and Allergan have also submitted an application to market ABP 215 in the European Union, and are currently awaiting a regulatory decision.

Below, Bruce A. Feinberg, DO, discusses factors that will affect the uptake of biosimilars among community oncologists. 

The FDA has approved Mvasi, the first biosimilar bevacizumab (Avastin). 

FDA Approves Mvasi, First Bevacizumab Biosimilar

Adello Biologics, a New Jersey-based biosimilar developer previously named Therapeutic Proteins International, 

 this week that its Biologics License Application (BLA) for a biosimilar filgrastim candidate has been accepted for review by the FDA. The company did not disclose a biosimilar user fee action date for a regulatory decision by the FDA.

Peter Moesta, PhD, CEO of Adello said, “If approved, we are excited to be able to offer an additional, important treatment choice that can prevent serious complications for patients.” 

Adello’s BLA includes data from a double-blind, single-dose, 2-period crossover pharmacokinetic (PK) and pharmacodynamic (PD) 

 of its product in comparison with the reference filgrastim. The study, which included 54 healthy volunteers, demonstrated that Adello’s product had similar PK and PD properties to the reference drug. Safety and immunogenicity were also similar between the 2 products.  

Reference filgrastim (Amgen’s Neupogen) is a granulocyte colony-stimulating factor used to treat or prevent chemotherapy-induced neutropenia. To date, 1 biosimilar filgrastim, Sandoz’s Zarxio, is available in the United States. 

Adello also reported that it is developing a biosimilar pegfilgrastim, referenced on Neulasta, and a biosimilar adalimumab, referenced on Humira, in addition to a number of other products that are currently in preclinical development. 

Adello Biologics, a New Jersey-based biosimilar developer previously named Therapeutic Proteins International, announced this week that its Biologics License Application (BLA) for a biosimilar filgrastim candidate has been accepted for review by the FDA.

Adello Biologics Submits BLA for Filgrastim Biosimilar

, policy experts addressed the question of how biosimilar developers can navigate the complex and challenging biologics marketplace in the United States.

Elizabeth Jex, attorney advisor in the office of policy planning for the Federal Trade Commission (FTC), moderated the panel discussion, titled “Market Access, Market Success,” which included presentations by Rachel Sher, deputy general counsel of the Association for Accessible Medicines; Crystal Kuntz, vice president of policy and regulatory affairs for America’s Health Insurance Plans; and Andrew Mulcahy, policy researchers and associate research department director of the RAND Corporation.

Jex, who noted that she was speaking as an individual rather than on behalf of the FTC, opened the discussion by saying that she was concerned that anti-competitive conduct, as well as challenges in the reimbursement system for biosimilars are—in stark contrast to the European experience&mdash;“chilling price competition” for biologic therapies in the United States.

During the discussion, several key themes emerged:

The panelists shared concerns that Risk Evaluation and Mitigation Strategies (REMS)—programs to manage potential risks of a drug&mdash;are being abused to withhold samples for testing. Under REMS programs, some biologics sponsors decline to provide samples of their products to biosimilar developers for testing, effectively erecting a barrier to biosimilar development.

“This is not at all what congress intended when it put the REMS authorities in place,” said Sher, noting that, even when the FDA does not require REMS for a drug, some reference product sponsors institute their own safety programs. When implemented, such programs can also restrict biosimilar developers’ access to samples.

Such strategies pose a serious risk to biosimilar developers; because biosimilar development is likely to involve a great number of samples in clinical trials; a study could fail if a developer is unable access the reference drug. “The situation with biosimilars is likely to be worse, going forward,” Sher said. For reference product sponsors, “the financial incentives in the biologics area are just so great that every day on the market without a biosimilar present is going to be worth it” to delay biosimilar entry.

The panelists expressed concerns that patent litigation has slowed the entry of biosimilar products in the US marketplace. Kuntz said that her organization filed an amicus brief last year in the case of 

with respect to delays caused by a 180-day waiting period to market a drug after a biosimilar developer provided notice of commercial marketing.

“This is an area of strong need,” said Kuntz. “We have very high-cost biologic drugs, and that’s an ongoing concern for our health plans. We wholeheartedly agree with the need to get [biosimilars] on the markets.”

has eliminated the 180-day waiting period, new concerns about inter partes review (IPR) loom for the industry; IPRs, proceedings before the Patent Trial and Appeal Board that provide for the review of patentability for 1 or more claims of a patent, have recently come under fire. According to Sher, some advocates for reference product sponsors have called for pharmaceutical patents to be exempt from IPRs.

Sher, who called IPRs both more efficient than traditional district court litigation in patent disputes and also subject to less judicial review after a decision, said that preserving the IPR process will be critical to clearing the way for biosimilar products to enter the marketplace.

Educating policymakers about biosimilars and the problem of high drug costs also poses challenges, said the panelists. According to Kuntz, when engaging with policymakers, “there’s still a perception that high-cost drug issues are one-off, unique drug issues. We have to continually emphasize that this is a problem across drug classes. It’s not the exception, it’s the rule.”

Mulcahy agreed that policy makers need more education about biosimilars, saying, “even for policymakers who are really engaged and steeped in these issues, you get in the weeds pretty quickly.” With respect to biosimilars and the challenge of market access, “There’s this urge to equate biosimilars and traditional generic drugs, and I think that’s a potential pitfall…there may be some analogues, maybe some lessons learned, but there maybe aren’t that many.”

Sher saw promise in the Creating and Restoring Equal Access to Equivalent Samples Act (CREATES Act), which offers some potential solutions to the problems facing biosimilars. Under the Act, if a contract of sale for testing of drug samples is not finalized within a set period, generic and biosimilar developers will be able to seek injunctive relief in court, and the FDA would receive greater authority to waive the requirement for a single, shared REMS system when appropriate. The bill, she said, could remove the incentive for reference product sponors to withould samples.

As for whether the Act could succeed in congress, “we are seeing an incredible bipartisan push,” said Sher. “It has a lot of political momentum at a time when bipartisanship is not all that common.”

At the 2017 AAM Biosimilars Council Conference, policy experts addressed the question of how biosimilar developers can navigate the complex and challenging biologics marketplace in the United States.

Policy Experts Weigh in on Market Access Challenges for Biosimilars

 today that the FDA has accepted its Biologics License Application (BLA) for a proposed rituximab biosimilar. The drug is referenced on Rituxan, which is approved to treat blood cancers and immunological diseases.

The BLA’s data package includes analytical, preclinical, and clinical data, including a pharmacokinetic and pharmacokinetic trial of the proposed drug in the ASSIST-RA rheumatoid arthritis trial phase 3 confirmatory safety and efficacy data from the ASSIST-FL follicular lymphoma study.

Sandoz says that it hopes its drug will, if approved, help reduce the high cost of biologic treatment. “The cost of treating cancer in the [United States] is a major concern for many patients and their families as well as for the healthcare system,” said Mark Levick, MD, PhD, global head of biopharmaceuticals development for Sandoz. “With the FDA acceptance of our regulatory submission for proposed biosimilar rituximab, we plan to…[free] up resources for and [support] patient access in other areas of cancer care including innovative therapies.”

 from the European Commission to market its rituximab biosimilar in Europe. Under the name Rixathon, Sandoz’s product is approved to treat all indications of the reference rituximab. Sandoz called the product 1 of 5 major launches the company has planned for the coming 4 years.

While the reference rituximab already faces competition from biosimilars in Europe, the global market for the drug has continued to grow; the branded drug 

 $8.58 billion for Genentech in 2016, an increase of 2.7% from its 2015 sales.

Sandoz announced today that the FDA has accepted its Biologics License Application (BLA) for a proposed rituximab biosimilar. The drug is referenced on Rituxan, which is approved to treat blood cancers and immunological diseases.
 

FDA to Review BLA for Sandoz Rituximab Biosimilar

 a new strategic partnership with Singapore-based GMS Tenshi Holdings. The agreement provides for the private placement of up to $25 million in Oncobiologics’ series A convertible preferred stock as well as 16,750,000 shares of common stock (with an aggregate price of approximately $15 million).

The agreement also includes a joint development and license agreement that provides GMS Tenshi the rights to ONS-3010, an adalimumab (Humira) biosimilar, and ONS-1045, a bevacizumab (Avastin) biosimilar in emerging markets exclusive of China, India, and Mexico. This new agreement replaces a previous arrangement between the companies that licensed only the bevacizumab biosimilar to GMS Tenshi, and resulted in payments to Oncobiologics of $2.5 million.

New Jersey-based Oncobiologics intends to use the proceeds of the private placement to initiate phase 3 clinical trials for its adalimumab biosimilar in 2018. The company says that it intends to pursue a designation of interchangeability with its product and the reference Humira.

“This investment by GMS Tenshi represents the culmination of our efforts to align with a strategic financial partner with a global strategy to accelerate commercialization of our biosimilar candidates and enhance our partnering and licensing capabilities,” said Oncobiologics CEO, Pankaj Mohan, PhD. “We believe that we now have a partner with the necessary financial and global commercial pharmaceutical expertise that…will allow us to realize our vision to bring affordable biologic drugs to patients in need around the world.”

Shares of Oncobiologics rose on news of the new partnership, ending last week at 

 per share (an increase of 126%). The company will need to secure stockholder approval of its agreement at its annual meeting, and will file a proxy statement with the US Securities and Exchange Commission in the interim.

In addition to the 2 drugs covered by its new agreement with GMS Tenshi, the biosimilar developer also reports 2 additional products in its 

: ONS-1050, a trastuzumab (Herceptin) biosimilar, and ONS-4010, a denosumab (Prolia, Xgeva) biosimilar. The company expects to initiate phase 1 trials for both products in 2018.

Biosimilar developer Oncobiologics has announced a new strategic partnership with Singapore-based GMS Tenshi Holdings.

Oncobiologics: New Strategic Partnership, Late-Stage Adalimumab Biosimilar Trials

How much money can biosimilar filgrastim save, and how can health systems encourage uptake? This infographic outlines 7 key concepts. 

Infographic: What You Need to Know About Biosimilar Filgrastim and Neutropenia

Oncology trials often report on progression-free survival (PFS) or overall survival (OS), but the authors of an analysis 

 during a poster session today at the European Society of Medical Oncology (ESMO) Congress argue that such endpoints are less sensitive then short-term overall response rate (ORR) in confirming biosimilarity when long median PFS or OS are expected.

The authors presented considerations on interpreting survival data as illustrated by a sensitivity analysis from a recent study of biosimilar rituximab. In a confirmatory phase 3 study, treatment-naïve patients with follicular lymphoma received either European Medicines Agency-approved GP2013 (n = 314) or reference rituximab (n = 315).

Patients who responded to an induction treatment with cyclophosphamide, vincristine, and prednisone chemotherapy received either GP2013 or reference rituximab as maintenance monotherapy.

The primary endpoint for equivalence was ORR at the end of induction. Secondary endpoints included PFS and OS.

As of December 2016, the median follow-up was 23.6 months for the GP2013 arm and 24.2 months for the reference rituximab arm. The study met its primary endpoints to confirm biosimilarity.

Median PFS and OS could not be estimated. Hazard rations for PFS and OS were 1.31 (90% confidence interval [CI]; range, 1.02 to 1.69) and 0.77 (90% CI; range, 0.29 to 1.22), respectively.

A Kaplan-Meier analysis showed that PFS survival curves diverged between 12 and 24 months, yet the curves ran parallel outside of that period, contrary to the proportional hazard assumption of the Cox model. Complete response (CR) rates were similar between treatments at all time points, including at 33 months.

The researchers concluded that a small sample size, a low event rate, data immaturity, and other aspects of study design can decrease a study’s sensitivity in biosimilarity assessments, as demonstrated by the fact that hazard ratios for PFS and OS had opposite directions, while CR rates remained similar across time.

PFS and OS results, the authors say, should be interpreted with caution, as they may not reflect either a difference or a lack of a difference between treatments.

Oncology trials often report on progression-free survival or overall survival, but the authors of an analysis presented during a poster session today at the European Society of Medical Oncology (ESMO) Congress argue that such endpoints are less sensitive then short-term overall response rate. 

Exhibit Caution When Interpreting PFS, OS Data in Biosimilarity Studies 

Here are the top 5 biosimilars articles for the week of September 4.

Number 5: A recent analysis shows that biologic agents represent the 

highest single cost associated with infusion therapy

USV announced that it has successfully completed phase 1 and phase 3 studies on a proposed pegfilgrastim biosimilar.

 The company expects to submit data to the European Medicines Agency before the end of the year.

The European Association of Hospital Pharmacists recently released a position paper

 on biosimilar medicines. The paper contains marked contrasts to the FDA’s current thinking about biosimilars in the United States.

state governors and insurance commissioners testified before the US Health, Education, Labor, and Pensions Committee

 on stabilizing the Affordable Care Act marketplace.

Celltrion has received the FDA’s Form 483 after a recent inspection

 of its manufacturing facility. The form notes 12 observations that include problems with vial stoppers of injectable drugs and visible particulate in products.

Finally, last week, our newsletter asked you to share your thoughts about whether the FDA’s recent approval of a second adalimumab biosimilar is likely to influence prescribing behavior. To view results of the poll, visit The Center for Biosimilars® 

The Center for Biosimilars recaps the top 5 stories in biosimilars news for the week of September 4, 2017.

The Top 5 Biosimilars Articles for the Week of September 4

The US Senate’s Committee on Health, Education, Labor, and Pensions (HELP Committee) held the first 2 of its 4 full committee hearings on stabilizing the Affordable Care Act (ACA)’s individual insurance market. 

 on Wednesday and Thursday were state insurance commissioners and state governors, respectively.

Across the 2 days of testimony, key themes emerged:

Funding Cost-Sharing Reduction (CSR) Payments

CSR payments provide financial assistance to consumers who make from 100% to 250% of the poverty line to help them cover copayments and deductibles. Paid in the form of subsidies to insurance companies, CSRs are provided for in the ACA. The Trump Administration has signaled that it might put an end to CSR payments, a move broadly opposed by those providing testimony in this week’s hearings.

Montana Governor Steve Bullock (D) said that “the Administration’s mixed—and at times hostile&mdash;signals regarding the CSR payments and other destabilizing actions has led Montana’s largest insurer to propose a rate hike for the next year that’s 10 times higher than it would have been under current provisions of the ACA.”

Massachusetts Governor Charles Baker (R) said, “month to month resuscitation of [CSRs] is not stabilization; [CSRs] should be maintained for at least 2 years.” Most of Baker’s peers agreed that CSRs should be extended until at least 2019, while Washington’s state insurance commissioner, Mike Kreidler, called for a permanent appropriation for CSRs.

Reinsurance programs provide payment to health plans that cover higher-cost participants as a way to insulate premiums from increasing by offsetting the higher cost of individual enrollees. Kreidler proposed enactment of a federal reinsurance program with a minimum duration of 3 years. He said that, while enactment of such a program now would likely not affect 2018 insurance rates, it would encourage insurers to participate in the 2018 market.

Teresa Miller, Pennsylvania’s acting secretary of the department of human services, said, “A $15 billion reinsurance program in the context of a careful, bipartisan approach to improving our healthcare system would be something I would view favorably, especially if the individual mandate were preserved and outreach was boosted to improve enrollment in individual market plans.”

The ACA provides the possibility of state waivers on portions of the ACA so long as they do not increase the federal deficit or reduce access to coverage. Miller joined many of her colleagues in calling for a streamlined waiver process that would allow states to adjust their policies to their constituents.

Governor John Hickenlooper (D) of Colorado further requested tax incentives for companies to enter counties with only 1 insurer on the exchange, while Utah Governor Gary Herbert (R) urged Congress to provide incentives that would appeal to healthier, younger enrollees in order to maintain broad participation in the individual marketplace. John Doak, commissioner of the Oklahoma Department of Insurance, argued for expansion of health savings accounts.

Governors and insurance commissioners were in agreement that healthcare costs must be addressed as part of the overall problem of affordable healthcare. Governor Bill Haslam (R) of Tennessee advocated for a shift to value-based care, saying that “one of the drivers of healthcare costs is the misalignment of incentives that is created when we compensate providers based on the volume of care they provide rather than on outcomes or efficiency.”

Miller called for bipartisan work on bringing down the cost of healthcare overall, saying “We need to have a serious national conversation about how we can moderate the unsustainable growth in healthcare costs, especially in areas experiencing astronomical growth in cost, like we currently see in pharmaceutical costs.” Baker, too, highlighted the growing cost of drugs, saying that pharmaceutical costs grew by 8% in his state last year.

Across party lines, commissioners and governors urged Congress to move quickly; Lori Wing&#8208;Heier, director of Alaska’s division of insurance, reminded Congress that insurers’ rate filings are to be approved next week, and that “Any decisions made after the filings are approved could cause unintended, unfavorable disruptions to insurance markets.”

The HELP committee will hold additional hearings on September 12, during which it will consider state flexibility under the ACA, and on September 14, when it will hear testimony from a variety of healthcare stakeholders.

The US Senate’s Committee on Health, Education, Labor, and Pensions held the first 2 of its 4 full committee hearings on stabilizing the Affordable Care Act’s individual insurance market. Testifying on Wednesday and Thursday were state insurance commissioners and state governors, respectively. Across the 2 days of testimony, key themes emerged.