The Center for Biosimilars Staff

The FDA has approved, to date, 7 biosimilar treatments. 

Articles

Infographic: The 7 FDA-Approved Biosimilars

Judge James C. Mahan of the US District Court denied the Pharmaceutical Research and Manufacturers of America (PhRMA) and Biotechnology Innovation Organization (BIO)’s motion for a temporary restraining order that would force Nevada to “cease and desist all action implementing or enforcing” contested sections of Nevada’s Senate 

SB 539, signed into law by Republican Governor Brian Sandoval, requires drug makers to annually disclose list prices for insulins, profits made, and discounts provided to pharmacy benefit managers. It also requires drug makers to explain spikes in insulin pricing. Trade groups PhRMA and BIO 

 the drug “unprecedented” and “unconstitutional.”

, Mahan indicated that the court could rule a temporary restraining order only if the moving party showed that immediate and irreparable loss or damage would result before the opposing party’s motion for a preliminary injunction could be heard. He called such a restraining order an “extraordinary remedy” that would not be granted without the plaintiff’s demonstrating the possibility of irreparable. Mahan said that PhRMA and BIO had not shown that they would suffer such damage, in part because the first disclosures from industry concerning drug pricing will not be due until July of 2018.

Now that the motion for the restraining order has been denied, the state will have until September 27, 2017 to file its reply to PhRMA and BIO’s motion for preliminary injunction.

Judge James C. Mahan of the US District Court denied the Pharmaceutical Research and Manufacturers of America (PhRMA) and Biotechnology Innovation Organization (BIO)’s motion for a temporary restraining order that would force Nevada to “cease and desist all action implementing or enforcing” contested sections of Nevada’s Senate Bill 539.

Pharma Groups Denied Restraining Order in Nevada Drug Pricing Lawsuit

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 18.

Number 5: Dr Stanley Cohen, medical director of the Metroplex Clinical Research Center and clinical professor of internal medicine at the University of Texas Southwestern Medical School, 

says that patients should feel comfortable about using biosimilars to treat rheumatic diseases.

low-level anti-tumor necrosis factor anti-drug antibodies in patients with inflammatory bowel disease may be overcome

 by dose escalation or the addition of an immunomodulator.

Number 3: An international, multidisciplinary task force has released 

8 consensus recommendations for the use of biosimilars

filed suit against Johnson and Johnson in a Pennsylvania district court.

 Pfizer’s complaint alleges that the Remicade sponsor has been using anti-competitive means to block sales of its biosimilar infliximab, Inflectra.

Number 1: Dr Angus Worthing, practicing rheumatologist and vice chair of the Alliance for Transparent and Affordable Prescriptions, says that 

rebates for reference biologics reduce competition and lead to higher drug prices for patients.

Finally, last week, our newsletter asked for your input on the size of the cost-saving potential that biosimilar filgrastim provides to health plans. To view results of our poll, visit The Center for Biosimilars® 

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

The Center for Biosimilars recaps the top 5 stories in biosimilars news for the week of September 18, 2017.

The Top 5 Biosimilars Articles for the Week of September 18

 its Biosimilar User Fee Act (BsUFA) rates for 2018. The Biosimilar User Fee Amendments of 2017 (BsUFA II) authorize the agency to assess and collect fees from applicants for biosimilar products from October 2017 to September 2022. The FDA uses the fees to expedite the review process for biosimilars.

Some of the 2018 rates represent substantial increases from those charged in 2017:

Initial biological product development (BPD) fees will increase from $203,810 in 2017 to $227,213 in 2018

Annual BPD fees will increase from $203,810 to $227,213

Reactivation fees will increase from $407,620 to $454,426

However, application fees will see some reductions: 

Fees for applications requiring clinical data will drop to $1,746,745 from $2,038,100

Applications not requiring clinical data will drop to $873,373 from $1,019,050

The 2018 fees include a new program fee of $304,162, but eliminates 2 fee categories: product fees ($97,750) and establishment fees ($512,200).

 its performance goals for the coming year. The agency plans to review and act on:

90% of original biosimilar biological product application submissions within 10 months of the 60-day filing date

90% of resubmitted original biosimilar biological product applications within 6 months of the receipt date

90% of original supplements with clinical data in 10 months of receipt

90% of resubmitted supplements with clinical data within 6 months of receipt

The agency also has plans to improve its performance with respect to original manufacturing supplements. In 2018, its goal is to review and act on 70% of manufacturing supplements requiring prior approval within 4 months of receipt. That percentage will increase by 5% per year until 2022, when the FDA plans to act on 90% of such supplements within the same timeframe. Manufacturing supplements that do not require prior approval will be reviewed, across all years from 2018 to 2022, within 6 months of receipt.

The FDA will also implement its program for enhanced review transparency and communication for original 351 Biologics License Applications. According to the FDA, the program is designed to promote efficiency and effectiveness of the first review cycle process for biosimilars, and to minimize the number of review cycles needed for an approval. Under the program, the FDA review team and the biosimilar applicant may follow a standard communication approach, or may reach a mutual agreement on the timing and nature of interaction and the information exchange between the 2 parties.

Under a standard approach, the agency will hold a presubmission meeting with the applicant to discuss the planned content of the application, the applicant will submit an original application, and the FDA will communicate substantive review issues in its Day 74 letter (or notify the applicant if no substantive review issues were identified). The BsUFA review period will begin at the end of the 60-day filing review period beginning on the day of the FDA’s receipt of the original submission. The FDA will communicate with the applicant mid-cycle in the review process to provide an update on the review’s status, and will also meet with the applicant late in the cycle. For applications that will be subject to an advisory committee meeting, the FDA plans to convene meetings not later than 2 months prior to the BsUFA goal date. The FDA plans to complete all inspections for applications in each program within 10 months of having received an application.

The FDA has published its Biosimilar User Fee Act (BsUFA) rates for 2018. The Biosimilar User Fee Amendments of 2017 (BsUFA II) authorize the agency to assess and collect fees from applicants for biosimilar products from October 2017 to September 2022.

FDA Releases BsUFA Fee Rates, Performance Goals for 2018

Samsung Bioepis has gained government clearance to begin a phase 3 clinical trial of its ranibizumab biosimilar in the Republic of Korea.

, the Korean Ministry of Food and Drug Safety (MFDS) has approved the company’s phase 3 clinical trial for SB11, a biosimilar product referencing Roche’s Lucentis, which is approved to treat neovascular age-related macular degeneration (AMD), macular edema following retinal vein occlusion, diabetic macular edema (DME), and diabetic retinopathy in patients with DME. The multi-center domestic trial will comprise 140 patients who have AMD.

Samsung Bioepis is not alone in seeking a share of the market for Lucentis; US-based Pfenex and the German company Formycon are also developing biosimilar ranibizumab.

This week, Samsung Bioepis also gained MFDS 

 to sell its adalimumab biosimilar, SB5, in the Republic of Korea. Samsung Bioepis 

 a marketing authorization for the same drug, referenced on AbbVie’s blockbuster Humira, from the European Commission (EC) on August 24, 2017. The company plans to sell its biosimilar as Imraldi in the European Union.

News of Samsung Bioepis’ ranibizumab trial and adalimumab approval follow last week’s progress for its biosimilar trastuzumab, SB3, referenced on Herceptin. On Friday, the European Medicines Agency’s Committee for Medicinal Products for Human Use adopted a positive opinion of the drug.

On EC clearance, Samsung Bioepis plans to market the drug under the name Ontruzant. In order to ensure a reliable supply of the trastuzumab treatment, the company plans to partner with multiple contracting organizations to carry out production of Ontruzant, a Samsung representative 

Meanwhile, the biosimilar developer fended off rumors of a split with its marketing and distribution partner, MSD, in the Korean market. 

 that representatives from Samsung Bioepis today denied reports that a drug licensing agreement with MSD for Brenzys (a biosimilar etanercept, referenced on Enbrel) and Renflexis (a biosimilar infliximab, referenced on Remicade) had terminated after disappointing sales of the 2 biosimilars. According to 

the cost savings provided by biosimilar therapies in the Korean marketplace typically do not exceed 10%, and have not produced rapid sales.

Eye on Pharma: New Clinical Trials, International Approvals for Samsung Bioepis

Last week, England’s National Health Service (NHS) 

 a commissioning framework for biological medicines, including biosimilars.

The framework, authored by the NHS’ Medicines, Diagnostics, Personalized Medicine Policy Team, explains that NHS England spent £16.8 billion ($21.6 billion) on medicines from 2015 to 2016, an 8% increase in spending over the prior year. Of the top 10 medicines prescribed, 6 are biologics. Using biosimilars could save the health system £200 million to £300 million ($270 million to $404 million) per year by 2020 to 2021, and those savings could be used to fund innovative treatments or improvements in care.  

The framework proposes that at least 90% of new patients be prescribed the “best value biological medicine” within 3 months of the launch of a biosimilar for a given reference product, and that 80% of existing patients be prescribed the “best value” medicine within 12 months of a biosimilar’s launch.

The authors point to the NHS’ successes with biosimilars over the past 10 years; 80% of NHS patients receiving infliximab are now treated with a biosimilar, and 58% of patients receiving etanercept are treated with a biosimilar. The cost savings achieved by the health system through using these biosimilar options total £160 million ($216 million) per year. However, uptake of biosimialrs has been uneven in England; the framework indicates that 2 NHS trusts, both located in London, had uptake levels of biosimilar infliximab of 25% and 99%. This difference in rates shows, the authors say, a “significant opportunity” to improve uptake of biosimilar medicines.

With biosimilar rituximab now available in the European Union, and with 

biosimilars of trastuzumab and adalimumab

 expected to be available in December 2017 and October 2018, respectively, “It is now important for the NHS to embed the principles of switching to the best value biological medicine into commissioning and clinical practice, if we are to [realize] the optimal rate and extent of savings associated with these medicines,” say the authors.  

The framework calls upon NHS commissioners to work with relevant stakeholders, including regional pharmacists and procurement specialists, and to partner with Regional Medicines Optimisation Committees (RMOCs) across England. RMOCs will coordinate with local providers to increase the use of the best value biologics, and will ensure that plans to transition to such medicines are in place by the end of 2017.

 are asked to keep up to date with local policies on switching to biosimilars, and should ensure that they know what they spend on biologic treatments. Finally, the framework also has a recommendation for patients: those receiving treatment with biologics should ask their healthcare providers if there are suitable biosimilar options that they may receive for treatment.

Last week, England’s National Health Service released a commissioning framework for biological medicines, including biosimilars.

NHS Releases Commissioning Framework for Biologics, Biosimilars

This month, the Pharmaceutical Research and Manufacturers of America (PhRMA) and the Biotechnology Innovation Organization (BIO), trade groups representing the biopharmaceutical and biotechnology industries, 

 that they are challenging Nevada’s Senate Bill (SB) 539 in district court litigation.

Passed in June 2017 by constitutional majorities in both the Nevada Assembly and Senate, the 

 was signed into law by Governor Brian Sandoval (R). Among other provisions, the law 

 drug manufacturers to annually disclose list prices set for insulins, profits made, and discounts provided to pharmacy benefit managers (PBMs). It also requires drug makers to explain insulin price increases that are above the prior year’s inflation rate (or twice the inflation rate of the past 2 years).

Manufacturers could face daily fines if they fail to provide the required data. The bill also permits pharmacists to provide patients with information about lower-priced alternative prescription options.

, the “unprecedented and unconstitutional Nevada law… interferes with the federal patent and trade-secret laws, deprives manufacturers of their property interest in their trade secrets, and improperly overrides the regulatory choices of every other state.” PhRMA and BIO are seeking a declaration from the court that sections of SB 539 are preempted by federal law, and that they violate the US Constitution. They also seek a preliminary and permanent injunction prohibiting implementation or enforcement of the provisions at issue.

“While the purpose of the Act is to control prices for diabetes drugs, neither the Act nor its legislative history explain how transparency will lower prices apart from impermissibly burdening manufacturers’ lawful exercise of federal patent rights. The Constitution entrusts national economic policy to Congress precisely to avoid such outcomes,” according to the group’s complaint.

 that the suit did not come as a surprise to his office, and that the state’s attorney general would “vigorously defend this existing state law which was passed with bipartisan majorities of both houses.”

Nevada’s law is not the only state-based drug pricing initiative to find itself the target of a lawsuit this month; trade group the Association for Accessible Medicines has filed a 

 in Maryland, claiming that the state’s House Bill (HB) 631 is unconstitutional.

HB 631, originally slated to take effect next month, would require the Maryland Medical Assistance Program to notify the state’s attorney general of increase in the prices of generic or off-patent treatments, and would authorize the attorney general to both demand drug makers’ records and impose penalties on manufacturers who violate the law.

This month, the Pharmaceutical Research and Manufacturers of America (PhRMA) and the Biotechnology Innovation Organization (BIO), trade groups representing the biopharmaceutical and biotechnology industries, announced that they are challenging Nevada’s Senate Bill (SB) 539 in district court litigation.

Industry Groups Sue Nevada Over "Unprecedented" Drug Price Transparency Law

At the AAM Biosimilar Council Conference 2017, Hillel Cohen, executive director of scientific affairs at Sandoz, disambiguated key terms in biosimilars.

Infographic: 5 Key Biosimilars Terms Defined

 that it had transferred its patents for its cyclosporine ophthalmic emulsion, Restasis, to the Saint Regis Mohawk Tribe. Allergan said in a statement that the Tribe now owns all Orange Book-listed patents for the dry eye treatment, and that the Tribe is filing for a motion to dismiss an ongoing inter partes review (IPR) on the basis of sovereign immunity.

Under the agreement, the Tribe will receive $13.75 million from Allergan when the agreement is executed, and an additional $15 million per year in royalties on sales of the drug. According to the Mohawk Tribal Council, “This is a viable and sound opportunity for the Saint Regis Mohawk Tribe to enter into the patent, technology and research sector as part of our overall economic diversification strategy.”

A spokesperson for Teva Pharmaceuticals, which is one of the companies challenging Allergan’s patents on Restasis, 

that Teva “will be interested to see what comments are made about this tactic by regulatory agencies.”

The rest of the pharmaceutical industry, taken by surprise by Allergan’s strategy, will likely also look with interest on how the United States will address this unusual tactic to block generic drug makers from creating competing versions of its product. Pharma may also look to Allergan’s example as a model for how to transfer their patents to sovereign entities in exchange for regular royalties.

While Allergan’s latest tactic may be novel, reference product sponsors have used other approaches to delay generic and biosimilar competition for some time. Among practices that have been called into question are the following:

In order for a generic or biosimilar maker to develop a product, the company will require access to samples of the originator product. Some drug makers, 

, inappropriately restrict competitors’ access to samples by implementing safety programs that restrict distribution of samples.

 This practice involves making slight alterations that hold no significant therapeutic value to an existing drug and patenting the resulting product as though it were a new drug. Changes to drugs under a product-hopping strategy might include a change of form from a short-acting capsule to an extended-release tablet.

 to the House Judiciary Committee, FDA Commissioner, Scott Gottlieb, MD, described pay-for-delay agreements as settlements in which drug companies resolve patent disputes by agreeing with generic drug makers to delay competitive products’ entry in exchange for payment. Gottlieb stopped short of saying that approach stymied 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.”

, complex generics like Mylan’s EpiPen, an epinephrine product, which was recently the subject of controversy when its price suddenly spiked, can attain “virtual immortality” when they make adjustments to delivery devices. Mylan’s patent-protected change to the EpiPen’s push-button injector device effectively allowed it to stave off competition.

AbbVie has protected its reference adalimumab, Humira, with what Goodwin attorney Robert Cerwinski, JD, has 

 “a veritable patent thicket.” While the majority of patent protection for Humira has already expired, AbbVie has secured additional patents to the product that biosimilar developers must litigate either in IPR proceedings or under the Biologics Price Competition and Innovation Act pathways, both of which can be lengthy and costly.

Last week, Irish drug maker Allergan announced that it had transferred its patents for its cyclosporine ophthalmic emulsion, Restasis, to the Saint Regis Mohawk Tribe. Allergan said in a statement that the Tribe now owns all Orange Book-listed patents for the dry eye treatment, and that the Tribe is filing for a motion to dismiss an ongoing inter partes review on the basis of sovereign immunity.

Pharma's Creative Strategies to Hold Off Generic, Biosimilar Competition

Samsung Bioepis’ trastuzumab biosimilar, SB3, referenced on Roche’s Herceptin, has been recommended for 

 by the European Medicines Agency (EMA). The drug received a positive opinion from the EMA’s Committee for Medicinal Products for Human Use (CHMP) for the treatment of early breast cancer, metastatic breast cancer, and metastatic gastric cancer. The biosimilar’s approval will now be referred to the European Commission, which will make a final determination on whether to grant a marketing authorization to Samsung Bioepis for the drug.

Christopher Hansung Ko, president and CEO of Samsung Bioepis, said, “Through relentless process innovation and an uncompromising commitment to quality, we remain dedicated to advancing one of the industry's strongest biosimilar pipelines, so that more cancer patients and healthcare systems across Europe will benefit from biosimilars.”

Samsung’s product, which the company plans to sell under the name Ontruzant and which will be marketed by MSD (known as Merck in the United States), is poised to become the first biosimilar trastuzumab available in the European marketplace. The reference Herceptin, approved in the European Union in 2000, is among the top-selling drugs in the global marketplace, having earned 

 billion in sales in 2016, and has remained unchallenged by biosimilar competition in Europe.

CHMP also issued a positive opinion for Boehringer Ingelheim’s (BI) adalimumab biosimilar for the treatment of rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, ulcerative colitis, axial spondyloarthritis, chronic plaque psoriasis, hidradenitis suppurativa, and panuveitis. BI plans to market the drug under the name Cyltezo.

Ivan Blanarik, senior vice president and head of therapeutic area biosimilars at BI, said, “The recommendation by the CHMP for Cyltezo is an important milestone for Boehringer Ingelheim, bringing us one step closer to providing our first biosimilar to healthcare providers and patients. Chronic inflammatory diseases can be incredibly debilitating and we are delighted that Cyltezo has the potential to improve the lives of many of these patients.”

BI’s biosimilar was approved by the FDA in August, though ongoing patent litigation with reference adalimumab (Humira) manufacturer AbbVie has made it unclear when the biosimilar could be made available for use.

 that it intends to seek a US designation of interchangeability with the reference drug, which earned AbbVie 

 billion in global sales in 2016. BI has begun to enroll patients in the first study to demonstrate interchangability of an adalimumab biosimilar with Humira. FDA guidance holds that interchangeable status will only be granted if the risk, in terms of safety or diminished efficacy of switching between the reference product and the biosimilar, is not greater than the risk of using the reference product without a switch. The agency also says that it expects manufacturers seeking interchangeable status to include data from switching studies, conducted in sensitive populations, that include at least 3 switches.

On Friday, the European Medicines Agency's Committee for Medicinal Products for Human Use issued positive opinions on 2 biosimilar candidates.