Tony Hagen is senior managing editor for The Center for Biosimilars

Tony Hagen

A real-world study of patients with breast cancer who received febrile neutropenia prophylaxis with biosimilar pegfilgrastim (Udenyca) or reference pegfilgrastim (Neulasta) has not only demonstrated comparable efficacy between the 2 products but also shown that large-scale comparisons of this nature can be done, according to a study presented at ASCO20 Virtual, the annual meeting of the American Society of Clinical Oncology.

Investigators said the study was driven in part by the ongoing efforts by CMS to spur advances in value-based care, particularly through the Oncology Care Model (OCM) and its follow-on, the Oncology Care First Model.

“We have learned through the [OCM] that there are savings to be found by reducing inpatient admissions and emergency department visits and controlling for things such as duplicate [laboratory tests]. However, it has become increasingly clear that further savings will require practices to evaluate their use of both cancer-directed therapy and supportive therapy,” they wrote.

Pegfilgrastim is typically used to stem the incidence of neutropenia, which is a common adverse event for patients undergoing chemotherapy. Pegfilgrastim expense amounts to 5.3% of the total cost of cancer care in the OCM, so trimming this expense via use of biosimilars has great potential for savings.

Investigators used the Integra Connect Value Monitor to perform the comparative effectiveness research at scale. This enabled them to perform a matched cohort analysis of patients with breast cancer receiving biosimilar vs reference forms of pegfilgrastim between January 1, 2017, and August 31, 2019. Patients were matched according to age, gender, OCM participation status, and date of treatment. Each biosimilar patient (n = 496) was matched to 5 Neulasta patients.

The rate of neutropenia was the efficacy end point, and neutropenia was defined as patients having an absolute neutrophil count (ANC) less than 1500 or the presence of an 

 code to classify neutropenia in the patient’s medical record.

The rates of neutropenia demonstrated by the biosimilar and reference product were similar at 28.6% and 29.1%, respectively (

“These rates are likely higher than those reported in the literature due to the very broad definition of neutropenia used in this study. Follow up will include neutropenia rates by grade,” including grade IV neutropenia (ANC < 500), investigators said.

 presented at this year’s ASCO meeting, investigators said that use of biosimilar pegfilgrastim in the OCM enabled them to reverse the upward trend in the cost of pegfilgrastim use. The rate was increasing at $292 per year and the biosimilar use from mid-2018 until mid-2019 contributed to a cost decline of $93 over the first year.

For more biosimilar news from ASCO20 Virtual, click 

Webster J, Scott JA, Smith H. Udenyca has equivalent efficacy to the pegfilgrastim originator in breast cancer patients receiving highly myelosuppressive chemotherapy. Presented at: ASCO20 Virtual; May 30-31, 2020. Abstract e19273. meetinglibrary.asco.org/record/190539/abstract

Articles

A real-world study helped show how pegfilgrastim biosimilar can improve savings in the Oncology Care Model and its successor, the Oncology Care First Model, according to findings presented at ASCO20 Virtual, the annual meeting of the American Society of Clinical Oncology.

More Savings Are Possible for Oncology Care Model, ASCO Study Says

to move forward with an application for FDA approval of an onabotulinumtoxinA (Botox) biosimilar, which they said would potentially be the first Botox biosimilar.

“This collaboration adds another high-profile, large-market, complex biologic, across both aesthetic and therapeutic categories, to our industry-leading biosimilars pipeline,” said Mylan President Rajiv Malik in a statement.

The emphasis on therapeutic categories suggests that the biosimilar may 

 with another product Revance has in development, daxibotulinumtoxinA, a novel botulinum toxin type A that the company also hopes will compete with the Botox reference product.

Mylan and Revance said their decision is based on feedback from the FDA indicating that the 351(k) pathway for biosimilar approval under the Public Health Service Act would be appropriate for this product candidate.

The 351(k) pathway allows for licensure “based on less than a full compliment of product specific preclinical and clinical data.” In other words, it’s an abbreviated licensure pathway that does not require a biosimilar company to duplicate all of the work done by the product originator company in order to obtain FDA approval.

The plan for an onabotulinumtoxinA biosimilar stems from a collaboration and license agreement signed by the 2 companies in February 2018 for development, regulatory approval, and commercialization of the product.

Revance is now eligible to receive a milestone payment of $30 million from Mylan and an additional $70 million in payments contingent upon reaching further clinical and regulatory achievements. Mylan would commercialize the product in the United States, Europe, and other markets worldwide.

“We are pleased with Mylan’s decision to opt in to the biosimilar to BOTOX development program, as it reflects our mutual confidence in the path forward,” said Mark Foley, president and CEO of Revance Therapeutics. “Assuming regulatory approval, it would allow us to financially participate in the short-acting neuromodulator market, while focusing our commercial efforts on creating the new, long-acting neuromodulator category.”

The decision to move forward with a regulatory application was delayed when Revance last year gave Mylan more time, until April 2020, to commit to developing and commercializing the proposed biosimilar.

Although onabotulinumtoxinA has a cosmetic use market, it also is approved for neurological-related incontinence, prophylaxis of headache for migraines, upper limb spasticity, cervical dystonia, and strabismus.

Although it is not fully clear how Revance’s daxibotulinumtoxinA and onabotulinumtoxinA products would be commercialized to avoid overlapping sales activity, Revance said it continues with clinical trials for injectable daxibotulinumtoxinA in therapeutic indications, including cervical dystonia (phase 3), upper limb spasticity (phase 2), and plantar fasciitis (phase 2).

results for this agent are expected in the second half of 2020 for the cervical dystonia and plantar faciitis studies.

After some delay, Revance and Mylan have decided to push forward with an FDA application for an onabotulinumtoxinA (Botox) biosimilar.
 

Revance, Mylan to File Application for Botox Biosimilar

 marketing authorization for Shanghai Henlius Biotech’s trastuzumab biosimilar candidate HLX02 for the treatment of HER2-positive early breast cancer, HER2-positive metastatic breast cancer, and previously untreated HER2-positive metastatic adenocarcinoma of the stomach or gastro-esophageal junction.

Following a review that began in June 2019, the EMA’s Committee for Medicinal Products for Human Use (CHMP) determined that the biosimilar candidate is highly similar in quality, safety, and efficacy to the reference product (Herceptin).

A final regulatory decision for marketing authorization from the European Commission is anticipated in 2 to 3 months following review of CHMP’s opinion. A positive decision would lead to marketing authorization in all EU member states and Norway, Iceland, and Liechtenstein, which are members of the European Free Trade Association, a group of non-EU European countries.

 biosimilarity of HLX02 to the reference product were released in November 2019. The biosimilar monoclonal antibody candidate will be marketed in Europe by Accord Healthcare Limited.

“We are very proud to receive CHMP’s positive opinion for HLX02,” said Scott Liu, cofounder and CEO of Henlius. “We look forward to launching HLX02 to provide an alternative high-quality and affordable treatment option for patients with HER2 positive breast cancer and gastric cancer.”

Henlius’ current product pipeline spans 20 monoclonal antibodies. The company launched a rituximab biosimilar (HLX01) in China last year and has trastuzumab (HLX02) and adalimumab (HLX03) biosimilar candidates under New Drug Application review. It also has a bevacizumab biosimilar (HLX04) undergoing clinical trials in China.

Henlius has also developed a mAb checkpoint inhibitor therapy (HLX10) for the treatment of advanced solid tumors and chronic hepatitis B infections. The drug is undergoing trials as monotherapy in the United States, Taiwan, and China and is intended, in particular, for tumors that show little response to anti—PD-1/anti–PD-L1.

 in combination with chemotherapy are underway for the treatment of locally advanced/metastatic esophageal squamous-cell carcinomas, squamous non—small cell lung cancer, and extensive-stage small cell lung cancer.

Henlius and Accord signed a deal in June 2018 that provided Accord with rights to market HLX02 in Europe, the Middle East, North Africa, and certain countries in the Commonwealth of Independent States, which is comprised of post-Soviet states in Eurasia. Accord specializes in the distribution of generics and biosimilars and has a sales presence in 80 countries.

"We are committed to ensuring oncology patients get access to safe, cost effective medicines and this CHMP positive opinion builds on our established expertise and extensive oncology treatment portfolio,” said James Burt, executive vice president of Accord.

Shanghai Henlius Biotech received a positive European review opinion for its trastuzumab biosimilar HLXO2 and anticipates marketing authorization in 2 to 3 months.
 

Henlius Receives CHMP Nod for Trastuzumab Biosimilar

Results of a study presented at ASCO20 Virtual, the annual meeting of the American Society of Clinical Oncology, confirmed the clinical equivalence of the rituximab biosimilar candidate ABP 798.

Efficacy results demonstrated no clinically meaningful differences, and safety and immunogenicity were found to be similar between the reference product and ABP 798, according to Dietger Niederwieser, MD, a professor of medicine and head of the Division of Hematology and Oncology at University Hospital Leipzig in Germany.

The safety profile for the biosimilar candidate also was similar to that of the reference product (Rituxan in the United States and MabThera in the European Union).

“Together with analytical, functional, and clinical [pharmacokinetic (PK)/pharmacodynamic (PD) findings], these clinical efficacy, safety, and immunogenicity results provide the totality of evidence to support similarity of ABP 798 with [reference] rituximab,” Niederwieser and other investigators wrote.

The biosimilar is the subject of a Biologics License Application 

 for review to the FDA in December 2019 by Amgen and Allergan, which are collaborating on multiple oncology biosimilars. Since that time, Allergan has been merged into AbbVie.

Rituximab is a CD20-directed cytolytic antibody that in the United States has been approved for the treatment of non-Hodgkin lymphoma, chronic lymphocytic leukemia, and rheumatoid arthritis.

Investigators enrolled rituximab-naïve adult patients (N = 250) with grade 1, 2, or 3a follicular B-cell lymphoma expressing CD20. They were randomized 1:1 to ABP 798 or reference rituximab at a dose of 375 mg/m

 every week for 4 weeks followed by repeated dosing at weeks 12 and 20.

The primary and secondary end points were efficacy as measured by the risk difference (RD) of overall response rate (ORR). Additional end points were trough serum concentrations and the percent of patients with complete depletion of CD19-positive cell count at day 8. Adverse events and immunogenicity, or the incidence of developing antidrug antibodies, were also measured.

Clinical equivalence for the primary end point was measured by comparing performance of ABP 798 with the one-sided, 95% upper and lower confidence limits of the reference product at week 28, with noninferiority margins established at —15% and 35.5%.

In the primary analysis, investigators found that the biosimilar candidate efficacy was within the predefined equivalence margins (lower, —1.4%; upper, 16.8%) and results at week 12 also supported similarity (–9.3%, 11.2%).

Serum concentrations over time were similar, meeting the PK end point. Investigators said the percent of patients with complete depletion of CD19-positive cell count at day 8 also was similar between the groups, indicating equivalent B-cell depletion between the biosimilar candidate and the reference product.

The adverse event (AE) profiles also were similar: 83.6% of patients in the ABP 798 cohort (n = 128) experienced any AE, and 10.9% experienced grade ≥3 AE; the respective AE numbers for the reference product were 75.4% (126) and 10.3%.  

“Overall, the severities of all AEs observed were within the grades of severity expected for the reference product; no new safety signals were identified,” investigators wrote. ABP 798 also passed the immunogenicity test. Investigators said there were no clinically meaningful differences between treatment groups with regard to the incidence of developing antidrug antibodies.

Niederwieser D, Hamm C, Cobb P, et al. Efficacy of ABP 798 compared with rituximab RP: results from the comparative clinical study in patients with non-Hodgkin lymphoma. Presented at ASCO20 Virtual, May 30-31, 2020. Poster 8044

The rituximab biosimilar candidate ABP 798 met primary and secondary end points for safety, efficacy, and immunogenicity in a study presented at ASCO20 Virtual, the annual meeting of the American Society of Clinical Oncology (ASCO).
 

Rituximab Biosimilar Demonstrates Similarity in ASCO Study

The idea that “resources affect who lives and dies” is cringeworthy, but this is a very real phenomenon that reveals itself in multiple ways throughout the US cancer treatment system, said Devika Das, MBBS, who presented at ASCO20 Virtual, the annual meeting of the American Society of Clinical Oncology (ASCO).

Biosimilars are part of the solution for a broken system in the United States, one that wallops health care consumers with higher costs each year while offering them uncoordinated, poorly navigated care that could be tuned up for much better results, said Das, clinical assistant professor of hematology and oncology at the University of Alabama at Birmingham and the Birmingham Veterans Affairs Medical Center.

 “A truly high-value drug is the one that costs the least and has the most benefit for our patients,” she said in a discussion of findings presented at this year’s ASCO meeting.

The pharmacy shelves and cooling cabinets are stocked with a variety of medicines, some of which fail to meet this standard, Das said. “What we need is more research focusing on value-based pricing, rigorous post-approval follow-up for efficacy and toxicity, and use of real world evidence in the creation of standardized treatment pathways.”

A brief look at cancer mortality statistics tells a lot of the story, she said. Das peered through the window of the Affordable Care Act (ACA) to show how death rates from cancer dropped dramatically as health coverage became available to 20 million more Americans starting in 2010. Mortality dropped further in states that expanded access to Medicaid under the ACA.

In states that did not expand Medicare, cancer mortality per 100,000 individuals dropped from 69.5 to 52.3 from 1999 to 2017, but in those that did expand, the rate dropped from 65.1 to 46.3 per 100,000. There were more pronounced declines for whites and blacks than for Hispanics, which bears investigation, Das said.

However, these numbers paint a clear picture of how expanded access to health care can make a huge difference in survival in just the oncology sector, she said.

Das swiveled the lens to view the access issue from another angle, that of the rising cost of drugs, particularly innovative specialty medications that, when launched, tend to command increasingly eye-popping prices.

It’s no secret that launch prices of drugs in the United States are rising, but a study presented at ASCO put a ruler next to these increases to measure drug costs in the United States versus those in European countries. Overall launch prices from 2009 to 2019 increased 212% in the United States, 58% in England, 49% in Germany, and 54% in Switzerland.

The 3 European countries have been far more successful than the United States in bringing down the cost of drugs post launch. Investigators included 42 drugs in this 

 and found that post-launch prices of 36 (86%), 40 (95%), and 38 (90%) drugs decreased over time in Germany, Switzerland, and England respectively. In the US, far fewer drugs decreased in cost after launch, investigators said.

The authors of this study, which also was presented at ASCO20 Virtual, remarked in their abstract that the United States could succeed in trimming the costs of cancer drugs if it adopted the same methods used to negotiate drug prices in Europe.

“Launch prices for cancer drugs are far higher in the United States than in Germany, Switzerland, or England. These price disparities continue to increase substantially after market entry, since cancer drug prices, in general, decrease over time in Europe and increase in the United States,” the authors wrote.

Targeted therapies, such as bevacizumab, which is available in biosimilar form, can be used to treat non—small cell lung cancer, but some patients don’t get to the point where a decision can be made to use one of these agents, Das noted in her review of data presented at the conference.

 of patients in the Veterans Health Affairs’ National Precision Oncology Program demonstrated that 117 patients with non—small cell lung cancer in a larger population that underwent next generation gene panel testing turned out to have actionable “smoking gun” gene variations. However, 49 (41.2%) “were not prescribed available targeted agents.”

This problem is not limited to government health programs. This scenario may sound familiar to many practicing oncologists in the United States, Das said. “Often we send out tests, they come back in 7 to 10 days, they are faxed to our offices, and then uploaded to our electronic medical record, with no alerts sent to providers.”

This disjointed system does not serve the patient’s best interests and makes access to appropriate care a more elusive goal. What’s needed, she said, is a complete systems redesign. “To truly fix health care, we need a 2-pronged approach of policy reform and health care delivery reform together. It will make innovation equitable and accessible to all.”

Learn more about ASCO20 Virtual by visiting our 

. Find out about how biosimilar pegfilgrastim lowered the cost of care in the Oncology Care Model by clicking 

Devika Das, MBBS, reviews the evidence presented at ASCO20 Virtual, the annual meeting of the American Society of Clinical Oncology, and concludes that some deep reforms are needed in oncology care to improve access.

Higher Value Oncology Care Is Needed, VA Doctor Says at ASCO

A trastuzumab biosimilar candidate (HD201, Tuznue) was shown to be highly comparable to reference trastuzumab (Herceptin) in study findings presented at ASCO20 Virtual, the annual meeting of the American Society of Clinical Oncology.

The biosimilar agent is the lead biosimilar candidate under development at Prestige BioPharma of Singapore, which also has bevacizumab and adalimumab biosimilars in clinical trials, as well as denosumab, aflibercept, eculizumab, and ipilimumab biosimilars in preclinical and discovery stages.

Prestige BioPharma has a regulatory application for Tuznue under review by the European Medicines Agency. The company has contracted with UK-based Mundipharma International to distribute the trastuzumab product in European markets and is seeking approval for all of the same indications as Herceptin. It has also entered into an exclusive 

with Pharmapark LLC to supply and commercialize the biosimilar in Russia.

Two clinical similarity trials of Tuznue were undertaken: TROIKA-I and TROIKA. In TROIKA-I, 101 healthy individuals were randomized to either Tuznue or EU or US Herceptin products. They each received a single 6 mg/kg intravenous dose over a 90-minute infusion. The intent was to measure pharmacokinetic (PK) and safety equivalency.

TROIKA-I demonstrated that the biosimilar was safe and well tolerated with PK comparable to Herceptin, investigators said.

The second study, TROIKA, was designed to compare safety, PK, and efficacy, based on the total pathological complete response rate (tpCR). This was a randomized, double-blind, multicenter phase 3 trial. Patients were given Tuznue or EU-Herceptin in combination with chemotherapy in the neoadjuvant setting followed by trastuzumab monotherapy in the adjuvant phase. There were 574 patients evaluable for response.

Investigators said 46.6% of patients in the Tuznue arm achieved tpCR versus 46.2% of patients in the Herceptin arm; 55.0% of patients achieved breast pathological CR in the Tuznue arm versus 53.4% in the Herceptin arm; and the overall response rate was 90.8% versus 89.4%, respectively. These results all demonstrated equivalence between the biosimilar and reference products, investigators said.

Further, PK trough levels met the predefined equivalency margins. The adverse event profile for the biosimilar also demonstrated equivalence in the head-to-head test. The incidence of serious adverse events was 5.6% for Tuznue versus 4.4% for Herceptin.

Investigators said a follow-up study for TROIKA is ongoing, and complete safety, immunogenicity, and survival data are pending.

Hii J, Pivot X, Mclendon K, et al. Establishing analytical and clinical similarity between HD201 and Herceptin. Presented at: ASCO20 Virtual Scientific Program; May 29-31, 2020. Abstract 579

Prestige BioPharma of Singapore has successful clinical trials to support its bid to market a trastuzumab, based on findings presented at ASCO20 Virtual, the annual meeting of the American Society of Clinical Oncology.
 

Prestige BioPharma's Trastuzumab Demonstrates Equivalence

Use of biosimilar pegfilgrastim amounted to significant cost savings in the Oncology Care Model (OCM), according to a study presented at ASCO20 Virtual, the annual meeting of the American Society of Clinical Oncology.

Investigators said they studied use of biosimilar pegfilgrastim since its introduction in mid-2018 until mid-2019 and found that it not only stabilized the increasing cost of pegfilgrastim per administration but also caused a decline in cost.

Specifically, cost of administration had been rising at the rate of $292 per administration per year over the 30 months since the start of the OCM in 2016. When biosimilar pegfilgrastim became available, the average cost declined by $93 over the first year.

“Pegfilgrastim is a key supportive care agent in oncology patients, providing significant febrile neutropenia prophylaxis for patients on chemotherapy. However, pegfilgrastim also accounts for 5.3% of the total cost of cancer care for all patients in the Oncology Care Model (OCM),” investigators said.

The study was funded by Coherus BioSciences, which introduced the pegfilgrastim biosimilar Udenyca in January 2019. Another biosimilar pegfilgrastim (Fulphila) was available from July 2018. A third biosimilar, Ziextenzo, was 

during this time but launched after the study period, in November 2019.

The study has additional significance because the cost of Medicare billings is one measure by which the 175 practices participating in the OCM are judged. It can affect the payment incentives or cuts they receive.

Medicare payment for pegfilgrastim is 80% of average sales price plus 6%. The average reimbursement was $3636 per administration prior to the introduction of biosimilars and $3543 after.

Investigators said that, across the country, 88,847 Medicare patients received pegfilgrastim in 2018, amounting to $1.39 billion in Medicare payments.

“Assuming the patterns we’ve detected in our OCM data sample can be applied to the general Medicare population, we have estimated that the introduction of biosimilars resulted in $4.8 million in savings (1.39%) compared with what the total reimbursement would have been without biosimilars in the market in Q4 2018,” investigators wrote.

They said this “bending of the cost curve” could result in savings of $79.1 million (5.7%) in 2019 and $157.9 million (11.5%) in 2020.

The savings are a combination of patients using biosimilars and the restraining effect that biosimilar use has on the cost of the reference product (Neulasta), investigators said. “The introduction of biosimilars has caused even the branded agent to stabilize.”

They suggested there is potential for greater savings, because 90.6% of patients in the second quarter of 2019 were still receiving branded pegfilgrastim. 

“Introduction of biosimilars has created enough pressure on the market to result in significant cost savings, increasing the overall value proposition of pegfilgrastim,” they concluded.

Webster J, Smith RE, Wieland D, et alCost savings of biosimilar pegfilgrastim in a Medicare OCM population. Presented at ASCO20 Virtual Scientific Program;May 30-31, 2020. Abstract e19362. https://meetinglibrary.asco.org/record/190722/abstract

A study presented at ASCO20 Virtual demonstrated the power of biosimilar pegfilgrastim to lower costs in the Oncology Care Model (OCM), where pegfilgrastim expense amounts to 5.3% of the total cost of cancer care.
 

Biosimilar Pegfilgrasim Cuts OCM Expense, ASCO Study Finds

Fresenius Kabi, which earlier this week announced a biosimilar application filing with the FDA, said it has signed an agreement with medac, a Wedel, Germany—based pharmaceuticals company, to market the adalimumab biosimilar Idacio in Germany, which is where it was originally launched in 2019. Adalimumab is used for the treatment of plaque psoriasis, ankylosing spondylitis, Crohn disease, and ulcerative colitis.

Based in Bad Homburg, Germany, Fresenius Kabi has a broad slate of pharmaceutical products and announced on Wednesday that the FDA had accepted for review its biologics license application for the pegfilgrastim candidate MSB11455, which references Neulasta. Pegfilgrastim stimulates the growth of infection-fighting cells, and oncologists use it to treat febrile neutropenia, which results from chemotherapy.

Medac specializes in products for the diagnosis and treatment of oncological, urological, and autoimmune diseeases. Frensenius Kabi 

 today that the companies had agreed to cooperate on serving the market for rheumatological care in Germany, utilizing medac’s sales distribution network.

Fresenius Kabi said that the partnership has sales potential because medac provides methotrexate for the parenteral treatment of patients with chronic inflammatory diseases, and methotrexate is often paired with adalimumab as a treatment regimen.

“The partnership between Fresenius Kabi and medac will offer patients and doctors new benefits and synergies in therapy offerings as well as consulting,” Fresenius Kabi said in its statement.

 for a pegfilgrastim biosimilar marks Fresenius Kabi’s first biosimilar regulatory submission for the US market. It has other plans for biosimilar launches in the United States, having already announced in 2019 that it had reached an agreement with AbbVie, the maker of reference adalimumab, to market Idacio in the United States in 2023.

 of $19.1 billion in 2019. It faces a field of multiple competitor biosimilars in 2023. Neulasta 

Fresenius Kabi has tapped pharmaceuticals distribution company medac to amplify sales of its pegfilgrastim biosimilar in Germany.
 

Fresenius Kabi Chips Away at Neulasta Market in Germany

for review its Biologics License Application for the company’s pegfilgrastim candidate (MSB11455), referencing Neulasta.

The application marks the company’s first biosimilar regulatory submission for the US market, although the company has previously announced that it has struck a deal with AbbVie to allow the company to market its adalimumab biosimilar in the United States in 2023.

Pegfilgrastim stimulates the body’s production of white blood cells to fight infection and is employed to reduce the incidence of infection associated with febrile neutropenia, an adverse effect of chemotherapy.

“Pegfilgrastim plays a vital role in oncology care, and this acceptance by FDA is an important step toward giving oncologists and their patients greater access by providing another option to help support the immune system following chemotherapy,” said Seema Kumbhat, MD, chief medical officer for Fresenius Kabi USA. Based in Bad Homburg, Germany, the company maintains a North American headquarters and research and development center in Lake Zurich, Illinois.

There are currently 3 pegfilgrastim biosimilars on the US market. They include Udenyca (Coherus BioSciences), Fulphila (Mylan/Biocon), and Ziextenzo (Sandoz). Market size for pegfilgrastim is 

 included in the BLA application demonstrate that the biosimilar pegfilgrastim is equivalent to the pharmacokinetic and pharmacodynamic profile of the reference product. Fresenius Kabi officials said the safety and immunogenicity profiles are also comparable to Neulasta.

John Ducker, president and CEO of Fresenius Kabi USA, said the company hopes to become a market leader for biosimilars in the United States, building on its accomplishments in other medicines. “In the United States, we offer oncologists the industry’s broadest portfolio of injectable medicines, and we look forward to bringing this experience to producing high-quality biosimilars,” he said.

 its biosimilar to adalimumab (Idacio) on the German market last year.

Fresenius Kabi USA announced that the FDA has accepted its biologics license application for the pegfilgrastim biosimilar candidate MSB11455.

FDA Accepts Application for Fresenius Kabi's Pegfilgrastim

Even if the Affordable Care Act (ACA) is ruled unconstitutional, the Biologics Price Competition and Innovation Act (BPCIA), which is part of that legislation and allows for biosimilar licensing, should be preserved, according to 

 argument filed by the Association for Accessible Medicines (AAM).

The Supreme Court’s deadline was this month for receiving briefs in the case of the constitutionality of the ACA. In December, the Fifth Circuit Court of Appeals agreed with a lower court that the individual mandate requiring individuals to purchase insurance under the ACA was unconstitutional, a move that put the survivability of the ACA and the BPCIA in doubt.

“FDA-approved biosimilars offer patients and taxpayers enormous cost savings on life-saving treatments,” said the AAM’s interim CEO and general counsel, Jeff Francer, in a statement. “If a constitutional challenge to some provisions of the Affordable Care Act (ACA) resulted in the invalidation of the entire ACA, including the BPCIA, a decade of progress by AAM and its members would be lost—and at a crucial moment.”

The AAM argues that biosimilars have the potential to save $54 billion or more for patients and health care systems over the next 7 years. The BPCIA is a tool for streamlining biosimilar approvals, and therefore it is a vital piece of legislation, according to the legal brief.

“The BPCIA is exactly the type of legislation that should not be declared invalid based on a constitutional challenge to another part of the same public law….The BPCIA stands on its own and serves an important public purpose that is entirely disconnected from the insurance-related provisions of the ACA that are challenged here," the brief stated.

At issue is whether the individual mandate can be “severed” from other provisions of the act. If not, the entire ACA could be thrown out and Congress would have to enact replacement legislation to repair the damage. The ACA comprises 10 titles, and the mandate is part of Title I. Judge Reed O’Connor of the US District Court for the Northern District of Texas originally held that the mandate was so interwoven with the rest of the ACA that it could not be severed. After reviewing the case, the Fifth Circuit agreed that the mandate was unconstitutional but left it up to the Supreme Court to decide the issue of severability.

Part of what happens to the BPCIA depends on how the Supreme Court interprets Congress’ original intent, Stacie Ropka, PhD, JD, said in a recent 

“Did Congress intend for the entire act to rise and fall together? Looking at the BPCIA, it was originally debated as, and is intended to be, a standalone bill with provisions that are not interwoven with any other provisions of the ACA. It was sort of shoehorned into the ACA at the last minute. Thus, there’s a credible argument that Congress intended the BPCIA to remain intact even if other provisions of the ACA are found unconstitutional,” said Ropka, who practices law with Axinn, Veltrop & Harkrider LLP of Hartford, Connecticut.

The AAM contends that the BPCIA “passes every test for severability.”

Fallout from a ruling adverse to the BPCIA would remove the FDA's authority to review and approve abbreviated biologic drug applications, Ropka said. It also would abruptly halt reviews in progress for biosimilar agents. Developers instead would have to seek approval under the traditional regulatory pathway, which is not designed for biosimilars specifically and would be more cumbersome.

A key element of the BPCIA is that it allows for a biosimilar patent dispute resolution process designed to resolve intellectual property issues prior to a product’s arrival on market. Without it, developers would be faced with having to launch products at risk of litigation, and this might dissuade them from bringing biosimilars to market, which in turn could reduce the level of competition in the drug marketplace and, ultimately, the consumer benefit from lower prices.

“It’s really hard to see what kind of benefit these biosimilar developers would gain if they decided to go on a more traditional approval pathway,” Ropka said.

Among the briefs filed in defense of the Affordable Care Act and, with it, the Biologics Price Competition and Innovation Act (BPCIA), is one from the Association for Accessible Medicines, which argues the BPCIA is vital to biosimilars market development.