Jackie Syrop

Each time biosimilar manufacturers proceed down the approval pathway laid out in the Biologics Price Competition and Innovation Act, commonly referred to as the BPCIA, they are vulnerable to patent infringement litigation from reference product sponsors (RPS), according to a 

 by Tasha Francis and Jenny Shmuel, PhD, 2 attorneys from the law firm Fish & Richardson. The earliest this patent litigation can begin is 21 days after the FDA accepts an abbreviated Biologic License Application (aBLA) from a biosimilar maker.

Two cases: Sandoz, Inc v. Amgen, Inc and Celltrion Healthcare Co v. Kennedy Trust for Rheumatology Research (both decided in 2014), established that biosimilar applicants can’t typically be sued before an aBLA is filed and clinical trials are still ongoing, because there is no immediate threat of injury to the RPS.

The BPCIA establishes steps for resolution of patent claims by the RPS and the biosimilar applicant, which is known as the “

.” The law requires the biosimilar applicant to provide the RPS with a copy of the biosimilar’s application to the FDA for review, as well as information about the biosimilar’s manufacturing processes, including all patents involved, no later than 180 days before the date of the first commercial marketing of the biological product. However, a judge presiding over litigation in federal court in 2016 between Amgen and Sandoz about the patent dance 

 that the patent dance is optional, and that compliance cannot be forced. The decision was appealed to the Supreme Court and is currently being reviewed, but it is an open question whether the courts will allow a RPS to sue for patent infringement when a biosimilar applicant refuses to provide any information on the existence or status of an aBLA.

Therefore, although the BPCIA states that applicants have 21 days after the FDA accepts their biosimilar application for review to bring a patent infringement suit, the practical issue remains that the RPS may not be aware it has a right to sue because there is no public posting when the FDA accepts an application for review. The only certain public posting about a biosimilar’s status is the FDA’s actual approval of the biosimilar drug; thus, the RPS would have to find out of the application’s acceptance by some other method. For example, if the biosimilar company is publicly traded the applicant may have a duty to inform shareholders when it files an aBLA application or when the FDA accepts filings for review. Press announcements by biosimilar applicants also provide information about FDA reviews of aBLAs.

Francis and Shmuel conclude, “At the earliest, a biosimilar applicant may be sued 21 days after its aBLA is accepted for FDA review, but the individual circumstances may in practice delay any infringement suit. Should the biosimilar applicant wish to delay suit, it should consider declining to engage in the patent dance and keeping FDA acceptance of the aBLA confidential as long as possible.”

Articles

Patent Infringement Litigation: How Early Can It Begin?

In a surprise decision, the FDA has delayed a ruling on the approval of Eli Lilly’s highly anticipated once-daily investigational rheumatoid arthritis (RA) drug baricitinib, instead issuing a 

 (CRL) to Lilly and its partner Incyte asking for additional clinical data on dosing and safety concerns. Lilly and Incyte disagree with the FDA’s conclusions and said more discussion with the agency might help speed the resubmission of data for the drug.

Baricitinib is a Janus kinase inhibitor currently in clinical studies for its effect on inflammatory and autoimmune diseases. Baricitinib had generated a good deal of excitement after the February 2017 publication of a 

 that showed baricitinib produced significant clinical improvements in RA symptoms compared with placebo and adalimumab (Humira) when combined with methotrexate for patients with inadequate responses to methotrexate alone. The study suggests baricitinib may be an effective oral alternative to adalimumab, which is an infusion.

“We are disappointed with this action,” the company said, remaining confident in the benefit/risk of baricitinib as a new treatment option for adults with moderate to severe RA.

Lilly and Incyte had submitted data on baricitinib to the FDA in January 2016, a majority of which was positive. The companies also submitted additional data from a long-term extension study that suggested the drug’s previously recorded positive effects could be maintained for at least 48 weeks. These positive data had led some analysts to project $1.8 billion in sales for baricitinib by 2022 if it had been approved.

The FDA had already extended its review period of baricitinib by 3 months. Analysts had expected the agency to approve the drug, especially after its 

The delay in approving baricitinib resulting from the FDA’s decision to issue a CRL will be good news, however, for Sanofi and Regeneron, whose interleukin-6 inhibitor sarilumab—another RA drug that is expected to potentially become a blockbuster&mdash;may be approved imminently by the FDA. The delay in baricitinib’s marketing also potentially benefits Pfizer’s RA drug tofacitinib citrate (Xeljanz), which was approved in 2016 but has not yet generated expected sales.   

In a Surprise Decision, FDA Further Delays Approval of Lilly's RA Drug

A bill called the “Improving Access to Affordable Prescription Drugs Act” (S771) was 

 on March 29, 2017, by Senator Al Franken of Minnesota and 15 co-sponsoring Democrats to improve the Affordable Care Act by bringing down the skyrocketing prices of prescription drugs, which the Senators state is one of the main reasons why healthcare costs are rising.

The bill seeks to tackle prescription drug costs by increasing transparency and accountability, boosting access and affordability of key drugs, spurring innovation, and increasing choice and competition. A companion bill [H 1776] with the same name was introduced in the House of Representatives by Rep. Jan Schakowsky of Illinois and 4 co-sponsoring Democrats.

The bill notes “much of the biomedical innovation motivating new drug discovery is supported by the National Institutes of Health (NIH) and other federal programs.” To better understand how research and development costs, manufacturing and marketing costs, acquisitions, federal investments, revenues and sales, and other factors influence drug prices, the bill requires drug makers to disclose this information, by product, to the secretary of the HHS, who in turn will make it publicly available.

The bill will examine how patient assistance programs affect drug prices and “the extent to which drug makers are using independent charity assistance programs to drive up profits.” It also allows the secretary of HHS to negotiate with drug companies to lower prescription drug prices for Medicare, which it is not currently allowed to do. HHS can only negotiate drug prices for Medicaid and the Department of Veterans Affairs.

In addition, the bill will do the following:

Task the HHS Office of the Inspector General to “monitor changes in drug prices and take steps to prevent drug makers from engaging in price gouging”

Allow wholesalers, licensed US pharmacies, and individuals to import qualifying prescription drugs made at FDA-inspected facilities from licensed Canadian sellers, and in 2 years, from countries that meet standards comparable to US standards

Create a $2 billion prize fund at the National Institutes of Health (NIH) to fund entities that develop superior antibiotics to treat serious and life-threatening bacterial infections and to fund research that advances such treatments and is made publicly available

Create a center for clinical research within NIH to conduct all stages of clinical trials on drugs that may address an existing or emerging health need and provide $10 billion in funding over 10 years

Make it illegal for brand-name and generic drugs makers to enter into anti-competitive agreements in which the brand-name drug maker pays the generic drug maker “to keep more affordable generics off the market”

Require that products awarded 3-year New Clinical Investigation Exclusivity must show significant clinical benefit over existing therapies manufactured by drug applicants in the 5-year period preceding the submission of the application.

Senate Bill Seeks to Improve Access to Affordable Rx Drugs

Adalimumab (Humira), the best-selling medication globally, is not worth its current price and doesn’t work as well as 2 of its competitors, according to a new 

 from the Institute for Clinical and Economic Review (ICER), an independent nonprofit organization that seeks to improve healthcare value by providing comprehensive clinical and cost-effectiveness analyses of treatments, tests, and procedures.

Overall, the report concludes, targeted immune-modulating (TIM) rheumatoid arthritis (RA) drugs work better than older treatments such as methotrexate, but the prices of TIMs detracted from ICER’s cost-effectiveness rating, which is based on a quality-adjusted life-year (QALY) analysis. According to ICER, most immune modulators exceed traditional cost/QALY analysis thresholds.

To be designated as cost effective by ICER, adalimumab’s net price would need to be at a 50% to 69% discount of the list price. None of its competitors, tumor necrosis factor (TNF)-alpha or other classes, hit ICER’s benchmark for value, per ICER’s report, 

Targeted Immune Modulators for Rheumatoid Arthritis: Effectiveness & Value,

AbbeVie, the maker of adalimumab, has taken issue with the report’s conclusions and said ICER’s methodology was flawed. Analysts say that while the report is not likely to have much of an effect on adalimumab’s sales for now, it might affect pricing decisions on forthcoming novel medications and the need for those novel medications with payers. The report could potentially also affect pricing on adalimumab’s biosimilars when they are marketed.

Humira had the highest per-QALY cost of the TNF-alpha inhibitors at $232,644; infliximab (Remicade) came in the lowest at $202,824. Tocilzumab (Actemra), an IL-6 inhibitor, had the lowest overall cost at $168,600 per-QALY cost. ICER’s report noted that based on head-to-head data on effectiveness versus adalimumab, etanercept (Enbrel) was comparable in lowering disease activity; certolizumab (Cimzia) and abatacept (Orencia) matched on a variety of measures. Tocilzumab was superior to Humira at decreasing disease activity and on one common assessment scale.

The report also included comparative analyses of 2 investigational RA drugs, baricitinib (Olumiant, JAK inhibitor) and sarilumab (Kevzara, an IL-6 inhibitor), which were superior to Humira at lowering disease activity and 2 other assessment tools.

ICER’s effectiveness analyses gave Humira a “C” rating. ICER’s endorsement for moderate certainty of incremental or better benefit generally requires that a treatment receive a B+ grade.

The report concludes that although all the TIMs evaluated substantially improved health outcomes compared with conventional disease-modifying antirheumatic drugs (DMARDs) alone, their additional cost led to cost-effectiveness estimates that were well above commonly cited thresholds for cost-effectiveness, and the discounts required to achieve these thresholds are greater than estimated current discounts from wholesale acquisition costs. Compared with the market leader adalimumab, most TIMs in combination with conventional DMARDs were more favorable (lower costs and higher QALYs), ICER said.  

Humira Not Cost Effective for RA, ICER Report Concludes

Neutropenia, a common complication in patients administered myelosuppressive chemotherapy for nonmyeloid malignancies, is 

 with granulocyte colony-stimulating factors (G-CSFs). A budget impact study comparing home-administration of tbo-filgrastim, filgrastim-sndz, and filgrastim suggests that increasing tbo-filgrastim and filgrastim-sndz utilization for patients who self-administer the drugs may offer a more affordable option for US payers.

Tbo-filgrastim (Granix) and filgrastim-sndz (Zarxio) are, respectively, a follow-on biologic and a biosimilar version of the reference G-CSF filgrastim (Neupogen), with comparable efficacy and safety. Researchers Holly Trautman, PharmD, MS, of Aventine Consulting, Marblehead, MA, and colleagues created a budget impact model to estimate increasing utilization of home (patient)-administered tbo-filgrastim and filgrastim-sndz in patients with nonmyeloid malignancies treated with myelosuppressive chemotherapy from a US payer perspective. They estimated the changes in drug costs associated with projected increases in market share of tbo-filgrastim from 5% to 10% and filgrastim-sndz from 10% to 12%, for a 1-million-member health plan. The overall budget impact was calculated over a 1-year period, along with the difference in per-member, per-year (PMPY) cost between current and future scenarios. One-way sensitivity analyses were also conducted. 

It was assumed that 20% of patients receiving short-acting G-CSFs were self-administrating the medications at home. All products were decided upon through pharmacy benefits (Tier 3 formulary status; patient co-pay of $54/prescription). The model assumed syringe replacement rates of 1% for tbo-filgrastim and 5% for filgrastim and filgrastim-sndz because of differences in stability.

The effective annual plan per-patient drug cost totaled between $17,249 and $27,657, depending on dose and presentation, for tbo-filgrastim; between $17,043 and $27,332 for filgrastim-sndz; and between $18,034 and $32,212 for filgrastim. The estimated overall annual plan cost associated with short-acting G-CSFs was $55,920,046 (PMPY, $55.92) in the current scenario and $55,346,277 (PMPY, $55.34) in the future scenario. Estimated cost savings totaled $573,769 (PMPY, $0.58). The authors said the model was most sensitive to changes in the overall proportion of patients self-administering G-CSFs at home and to the wholesale acquisition cost for filgrastim.

Based on their analysis, the authors concluded that the effective annual plan per-patient drug cost for tbo-filgrastim and filgrastim-sndz was 14% to 15% lower than for filgrastim. “Estimated annual US health plan cost savings were in excess of $0.5 million overall, or $0.50 PMPY following small shifts in market shares,” they noted.

The authors presented their findings at the annual meeting of the Academy of Managed Care Pharmacy in Denver, Colorado, March 27-30, 2017.

Study Evaluates Budget Impact of Filgrastim and Similar Biologics for Treating Neutropenia

 submitted to the US Supreme Court on March 31, 2017, Sandoz asked the Court to reverse the decision of the US Court of Appeals for the Federal Circuit on the Biologics Price Competition and Innovation Act (BPCIA), 

Sandoz, Inc. v. Amgen, Inc. and Amgen, Inc. v. Sandoz, Inc., U.S., 

Nos. 15-1039 and 15-1195) concerns Sandoz’s filgrastim-sndz (Zarxio), biosimilar to Amgen’s filgrastim (Neupogen), and the companies’ dist inctinterpretations of the portion of the BPCIA that created a faster pathway of approval for biosimilars. The Court’s decision will likely affect how quickly biosimilars are released to the US market and how long innovators can remain the sole marketer of the drug.

Sandoz’s brief states that “Sandoz agrees with Amgen that the Biosimilars Act should be applied ‘as written.’ But that means applying the statute as written 

—not just the parts Amgen rips from context and reads in isolation.” At issue are 2 BPCIA provisions, one of which requires the biosimilar applicant to give the biologic reference product sponsor (RPS) its biosimilar application and manufacturing information and to work with the sponsor on a list of the RPS patents that might be infringed; the other requires the applicant to give the RPS notice 180 days before it intends to start selling the biosimilar.

The Federal Circuit court awarded a split decision, with each side winning on 1 issue. It agreed with Sandoz and the district court that the exchange of information was optional, but disagreed with its ruling on the 180-day notice, agreeing with Amgen that the statute means the applicant can’t give notice of commercial marketing until after the FDA has approved the biosimilar for marketing, therefore delaying Zarxio’s release for 6 months.

Sandoz petitioned and Amgen cross-petitioned the Supreme Court for review. Each party requesting that the Court reverse what was unfavorable to them. The Court granted both petitions review and each side submitted opening and reply briefs.

Sandoz’s reply brief said the BPCIA, as written by Congress, lays out different routes to resolving litigation and specific consequences. Sandoz said that each step specified in the Act was a mandatory condition precedent to continuing the process, and contends that Amgen’s interpretation of the BPCIA disregards the statute’s consequences for not following them. Sandoz said it was not Congress’s intention to inject a second timing element into the statute— that there be no notice until after FDA approval. Furthermore, Sandoz said Amgen’s interpretation of the BPCIA is also contrary to the law’s purpose that patent litigation should be resolved early and not delay biosimilar competition. The brief labeled as “fantasy” Amgen’s warning that Sandoz’s BPCIA interpretation would lead to chaos, causing attorneys for RPSs to rush into litigation prior to knowing what patents were being infringed and when the product was launching.

Amgen must submit its final brief to the Court by April 14, 2017. Oral arguments are scheduled for April 26, 2017, with a decision expected by the end of June.

Sandoz Brief Addresses US Supreme Court in Case Against Amgen

Scott Gottlieb, MD, President Donald J. Trump’s nominee for FDA Commissioner, 

 before the Senate Committee on Health, Education, Labor & Pensions at his confirmation hearing today that he would be an impartial and passionate advocate for public health. In his opening statement, he said that he would seek the most “bang for our regulatory buck” while being cognizant of risks and being sure to not add to consumer costs without improving consumer safety. He stressed his belief in the “gold standard of safety and efficacy” at the agency and said he hopes to expand approvals of generic drugs to lower US drug prices. “I think there are ways to modernize clinical studies without sacrificing the gold standard,” Gottlieb said.

A fellow at the American Enterprise Institute and former deputy commissioner of medical and scientific affairs at the FDA, Gottlieb has held 

 at the CMS under former President George W. Bush. He has expressed opposition to many FDA regulations, including FDA efforts to regulate diagnostics that could impact innovation. During the 2016 Patient-Centered Oncology Care meeting hosted by 

 possibilities for repealing and replacing the Affordable Care Act, including fewer restrictions on what he called “very tight actuarial banding” that “doesn’t allow for experimentation in benefit design.”

Gottlieb has been involved in venture capital and investment banking firms that invest in biomedical startups, and has his own consulting firm. He has served on numerous boards of pharmaceutical companies, which has helped him gain the support of pharmaceutical industry leaders but simultaneously raised concerns among critics worried about conflicts of interests. Gottlieb has 

 to recuse himself from issues related to the nearly 2 dozen companies he has ties to, and said he would divest himself of medical company stocks and would resign from his other positions.

 about streamlining the generic drug approval process and has advocated the end of drug rebates as a way to lower drug prices. “If insurers could demand up-front discounts, rather than back-ended rebates, and drug makers were free to offer them, then more of the markdown would come in the form of lower opening prices,” he stated in a September 2016 column.

In response to questioning from Senator Patty Murray of Washington about whether the FDA under Gottlieb would exercise independent, science-based decision making, Gottlieb said that would be his goal because people’s lives were at stake. “I’ll be guided by the science and by the expertise of the career staff,” he said. Murray noted Gottlieb’s financial ties to companies that she said have 60 drugs that could come before the FDA. When asked by Senators if he would resist FDA staffing cuts proposed by President Trump, Gottlieb said, “I’m going to be committed to advocate for a strong FDA, for strong resources at the FDA,” and said he hadn’t been shy about expressing his views to bosses.

Gottlieb said his first priority as FDA Commissioner would be findings ways to fight the opioid crisis, which required dramatic action. He called for reevaluating the way FDA currently develops alternatives to opioid drugs, and how the agency views medical devices and medically assisted therapy for people struggling with addiction.

Nominee for FDA Commissioner Vows to Strike Balance Before Senate Panel

Mucosal healing has emerged as an important therapeutic endpoint in the management of inflammatory bowel disease IBD, but few clinical trials have incorporated it as an outcome, and limited data exist to guide the selection of therapy based on comparative effectiveness in achieving this endpoint.

A recent review of FDA-approved drugs that treat IBD concludes that biologic treatments not only relieve IBD symptoms, they also maintain intestinal health. The study, published on March 22, 2017, in 

 aimed to examine the efficacy of each therapeutic class of FDA-approved IBD drugs in inducing and maintaining mucosal healing in moderate to severe Crohn’s disease (CD) and ulcerative colitis (UC) by performing a meta-analysis of existing data on these therapeutic endpoints.

Researchers led by Aurada Cholapranee, MD, of the Department of Internal Medicine at Montefiore Medical Center, New York, analyzed the following medications: azathioprine (Imuran), methotrexate (Trexall), mercaptopurine (Purinethol), infliximab (Remicade), adalimumab (Humira), certolizumab (Cimzia), golimumab (Simponi), natalizumab (Tysabri), and vedolizumab (ENTYVIO). These medications comprise drug classes of immunosuppressive agents, anti-tumor necrosis factor alpha (anti-TNF), and anti-integrin monoclonal antibody therapy.

The meta-analysis was conducted using 12 randomized, controlled trials that included studies of both induction and maintenance for UC and CD. The follow-up durations were 6 to 12 weeks for induction and 32 to 54 weeks for maintenance trials. 

The researchers concluded that, in general, the biologic treatments Remicade and Humira, both of which target TNF-alpha, were much more effective at maintaining mucosal healing in CD compared with placebo controls (28% versus 1%, respectively). With respect to UC, medicines targeting both TNFs and integrins (proteins involved in cellular adhesion and stability) were more effective than placebo controls in inducing (45% versus 30%) and maintaining (33% versus 18%) mucosal healing.

The investigators found that in UC, Humira was inferior to Remicade for the induction of mucosal healing; both medications were similar for CD. “We demonstrated that both anti-TNF and anti-integrin biological agents are effective for inducing and maintaining mucosal healing in UC, and anti-TNF therapies in CD,” the authors concluded. But between-drug differences in efficacy do exist within each therapeutic class, they noted, particularly for induction of mucosal healing in UC, with Remicade or combination therapy being the preferred strategy.

The researchers noted that there is an important and urgent need for data demonstrating efficacy of all approved agents in achieving mucosal healing to truly inform comparative effectiveness and patient care to achieve better outcomes.

Biologics Superior for Relief of IBD Symptoms and Maintenance of Intestinal Health 

Almost a year after the Indian Central Drugs Standard Control Organization issued new guidance for biosimilar drug development that eases the required procedures for bringing drugs from clinical trials to market, a 

 among Indian companies to develop biosimilars. Indian pharmaceutical companies dominate the global generic drug market and are poised to develop biosimilars—copies of large, complex biologicals&mdash;with annual sales of up to $60 billion as they go off patent in advanced economies.

Kiran Mazumdar Shaw, chairman and managing director of India-based Biocon, said the United States and Europe are seeking ways to combat the high prices of biologics, and biosimilars are a segment of the industry with rich margins. “I think that’s a compelling reason why people want to get into biosimilars,” she said. KPMG consultants estimates that the global biosimilar segment is expected to increase the value of sales at list prices from $2 billion in 2016 to $12.1 billion in 2020. The Indian biosimilar market is forecast to increase from $186 million in 2016 to $1.1 billion in 2020.

However, the manufacturing process for biosimilars is much more complex and expensive than for generic drugs. Biosimilars also accrue higher clinical trial costs than generic entities. Thus, the investment needed for development of biosimilars is much 

: $1 million to $4 million for generics versus $100 million to $250 million for a biosimilar. The cost savings are much larger for generics than for biosimilars: biosimilars generally cost 15% to 30% less than the reference biologics, whereas generics cost 50% to 90% less than branded drugs, which may be a factor that slows down adoption of biosimilars.

 FDA approval of pegfilgrastim (its biosimilar of Amgen’s Neulasta)—it is 1 of 6 biologics co-developed by Mylan and Biocon for global marketing, and more products are planned, according to Biocon’s Shaw. She expects biosimilars to contribute to about 20% of the company’s top line when they get regulatory approvals in the United States and Europe. 

 increased research budgets to focus on biosimilars over the next few years. Cipla has dedicated $130 million to the effort, Aurobindo announced a doubling of its research budget to $80 million with a focus on biosimilars, and Dr. Reddy’s is already developing 2 new biosimilars (trastuzumab for breast cancer, a biosimilar of Genentech’s Herceptin; and bevacizumab for metastatic kidney cancer, a biosimilar of Genentech’s Avastin). Reliance Life Sciences purchased global rights for biosimilars of infliximab from Epirus Pharmaceuticals, and Zydus Cadila is collaborating with a Turkish pharma company to market biosimilars in the Turkish market.

Biocon, in partnership with Japan’s Fujifilm Pharma, already markets the insulin analog glargine in Japan, which is embracing biosimilars to keep healthcare costs down for its rapidly aging population. Biocon’s concentration in diabetes and oncology will drive the company to continue to seek partnerships with other companies that have valuable assets in diabetes, cancer, or immune oncology, Shaw noted.

It remains to be seen what changes the new administration will bring to the table, but the US healthcare depends strongly on generics, Shaw points out, and needs affordable biopharmaceuticals to lower healthcare costs. “India is a strategic partner for the US in its healthcare models—in drug innovation, drug development, and finally developing these affordable drugs for the US market,” she points out. As regulators in the US and Europe become more comfortable with biosimilars, she says, the pathway will likely clear and costs of production will come down. Shaw believes India has a rich pool of talent in biotech and the life sciences, and there is no reason for Indian companies to miss the huge opportunities that biosimilars represent.

Indian Generic Pharma Companies in a Race to Develop Biosimilars

Following the FDA’s approval of Roche’s multiple sclerosis (MS) treatment ocrelizumab (Ocrevus), the company 

 when it placed a $65,000 list price on the new drug, leading to comparisons with its MS drug competitor, and more expensive rival, Merck’s interferon beta-1a (Rebif), which has a list price of $86,000. The annual price announced for ocrelizumab represents a 20% discount to the average price of other MS medications, Roche 

, stating that the industry needs to start to reverse the trend of rising MS drug prices, which have grown by 400% over 12 years, according to the National MS Society.

A Roche spokesperson noted that ocrelizumab was shown to be clinically superior to interferon beta-1a in phase 3 studies that compared patient responses to the 2 drugs. Ocrelizumab reduced the annualized MS relapse rate by 50% compared with interferon beta-1a, over a 2-year period.

Merck rejected any direct comparison between pricing for the 2 medications, calling it misleading and oversimplified to do so, because both drugs have different modes of administration and are typically managed separately by payers. Therefore, the access and pricing approaches are different. According to Merck, ocrelizumab is an infusion medication and is “expected to be covered under the medical benefit, and won’t typically require the manufacturer to provide discounts to payers.” Self-injection biologics such as interferon beta-1a, however, are often covered under the pharmacy benefit, Merck asserts, and their list prices often “bake in” room for manufacturer discounts to support access for patients.

It isn’t yet apparent if this distinction will prevent prescribers and patients from moving to the new drug, especially with the clinical data showing superiority of ocrelizumab for relapsing-remitting forms of MS. Experts have predicted ocrelizumab will be a potential blockbuster, with $4.1 billion in sales by 2022. Further, it is the 

 to treat primary progressive MS, potentially helping the drug achieve significant market adoption.