Stanton R. Mehr

Celltrion presented data at the American College of Rheumatology (ACR) meeting on November 14, demonstrating that its product CT-P10 is as safe and effective as Rituxan for the treatment of rheumatoid arthritis (RA).

, investigators tested CT-P10 against both US- and EU-licensed versions of rituximab. The study evaluated pharmacokinetic and pharmacodynamics, as well as safety.

Three hundred seventy-two patients participated in the study. A total of 161 were given CT-P10 and the remainder were given the originator product.

The investigators concluded that the pharmacokinetics of CT-P10 were highly similar to those for the originator products (90% confidence intervals were within the equivalence range of 80% to 125%), and the safety profile was noninferior. Infusion-related reactions occurred in 6 (9.4%) of patients in the biosimilar group, 4 (6.2%) in the US-licensed version of rituximab, and 12 (20%) in the EU-licensed group, and all of these reactions were either grade 1 or 2. Discontinuations as a result of an adverse event occurred in 3.1%, 4.6%, and 1.7% of patients taking the biosimilar, US version, and EU version, respectively.

 at the American College of Rheumatology meeting,  a team of researchers sought to gather efficacy data on the biosimilar versus the two licensed versions of Rituxan, using the DAS28-CRP/ESR as a primary endpoint.They found in this phase 3, controlled study, that the biosimilar was therapeutically equivalent to the other treatment groups, with a change in DAS28-CRP of -2.14 for the biosimilar vs. -2.09 for the originator products. Additionally, the change in DAS28-ESR scores were -2.41 vs. -2.35, respectively. ACR 20, 50, and 70 scores were equivalent as well. No significant differences in adverse events were detected among the groups, and no serious complications were reported.

Biosimilar rituximab is being tested not only in patients with RA but in those with non-Hodgkin’s lymphoma (NHL), chronic lymphocytic leukemia (CLL), and polyangiitis. If it is approved for treatment, Celltrion’s product would likely be the first CD20-inhibiting monoclonal antibody to reach the market in a biosimilar version.

Celltrion announced that on November 17, 

 for use in South Korea for non-Hodgkin’s lymphoma, chronic lymphocytic leukemia, and rheumatoid arthritis. It will be marketed under the name Truxima in that country.

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Pharmacokinetics of CT-P10 were highly similar to originator products. 

Ritumixab Biosimilar Demonstrates Positive Results in Rheumatoid Arthritis

If the Acting US Solicitor General’s recommendation is accepted, the US Supreme Court will rule on the validity of the timing of the 180-day notification rule as well as on the so-called 

The amicus brief was filed on December 7, in response to a lower court decision on 

, in which the plaintiff did not take actions consistent with the patient dance in readying Zarxio for the market. The lower court ruling, which stated that Sandoz could not file the 180-day notification of its intent to market Zarxio until it received FDA approval, prevented the biosimilar manufacturer from launching until September 2015, 6 months after receiving approval. Immaterial to patent litigation, which begins years before FDA approval (and seems to extend well beyond the notification period in most US cases), this was essentially an additional 6-month period of exclusivity, which was not the intent of the Biologic Price Competition and Innovation Act. In other words, if a manufacturer wanted to launch while still embroiled in patent litigation, that drug maker should be able to do so, “at risk,” which is the position taken by Pfizer and Celltrion in launching Inflectra™. The argument was made that the 180-day notification should be permitted earlier in the process, for instance, when it applies for FDA approval, so it does not interfere with product launch.

Although Zarxio is already on the market, Sandoz has other biosimilars in various stages of approval and development that are still subject to the lower court ruling (e.g., its etanercept biosimilar has been approved, but is awaiting the 180-day period before marketing in 2017).

If the Supreme Court takes up the recommendation, it is likely to hear the case during the current term and vote on it by July 2017.   

Supreme Court will rule on the validity of the timing.

Breaking News: US Asks Supreme Court to Rule on Biosimilar Patent Dance

Consider the following situation: the Food and Drug Administration (FDA) has approved biosimilar-xxyy (no matter for which disease).

The main questions of structural and molecular similarity have been answered by the FDA. The clinical trials for one indication show no clinically meaningful difference compared with the originator drug, and the FDA approves extrapolation to second indication for a different class of disorder.

Assuming the payer will make a decision to cover this agent on a preferred copayment tier for this self-administered biologic, physicians will now have to make their own decisions as to which patients might benefit most from therapy with this biosimilar, and in whom it might be safest, from their point of view, to start prescribing it.

We speak constantly today about overcoming barriers to physician uptake of new biosimilars. A large part of this involves education and information. Their sources of information on biosimilars will be only slightly different than the information pipeline for any biologic. The difference is that this is a biologic, and professional societies (and even patient groups) may have taken a stand to be extra cautious about its use.

Without pressure from payers to switch patients who are stable taking the originator product, it will then be a physician-based or patient-physician decision. Logically, this will be limited to patients who have not been treated with biologics in the past. For these patients, the risk of immunogenicity or adverse events is really no different than if they received the originator product for the first time. And a conversation will often take place with their colleagues about whether they had used the biosimilar, and was the outcome as intended.

However, another conversation that may well take place before prescribing is between the physician and the practice manager. The content of that discussion may be of an administrative nature, such as, “if I order this drug, will it be reimbursed without any problem?” In the case of a payer who has not yet held a Pharmacy & Therapeutics (P&T) Committee meeting to determine coverage, the same question may be asked but more urgently. “Do we even know what the patient copay may be? Do we have to acquire additional prior authorization approvals?” Additionally, the practice manager will wonder whether the biosimilar manufacturer has set up a “hub” to offer the payment and access assistance needed to smoothly order and deliver the product.

Ensuring the comfort of the practice manager is sometimes given too little consideration. This can go a long way to easing the physician into prescribing biosimilar-xxyy for that first patient.

Physicians will make their own decisions as to which patients might benefit most from biosimilars therapy.

The Foundation for Building a Clinician's Confidence Over a Biosimilar Drug

As reported in July, Sandoz received a complete response letter from the US Food and Drug Administration (FDA) in regard to its pegfilgrastim biosimilar application, 

. On its third-quarter earnings call, Novartis provided 

 for FDA’s rejection of this biosimilar. Apparently, further data are required. 

Novartis’ Sandoz unit has several additional biosimilar assets, including its marketed filgrastim-sndz product Zarxio, its recently approved biosimilar to Enbrel, and its investigational infliximab biosimilar (purchased from Pfizer after that company’s acquisition of Hospira). 

Vasant Narasimhan, MD, Novartis’ Global Head of Drug Development and Chief Medical Officer, confirmed, “As noted in the second quarter, we did receive a complete response letter and are continuing to engage in discussions with those at FDA and with EMA. In the US, we have agreed with the FDA to move forward on an additional study to address their data request. We would expect to submit that study to the FDA in 2018.” 

 The biosimilar partnership between Momenta Pharmaceuticals and Mylan took another step recently, when they announced the commencement of its phase 1 study of M834, a biosimilar of 

, will evaluate the pharmacokinetics, safety, and immunogenicity of this biosimilar in comparison with both the US and EU-licensed versions of Orencia in healthy volunteers. This is the 

 in the Momenta—Mylan partnership to reach the clinical trial stage.

Sandoz received a complete response letter from the US Food and Drug Administration (FDA) in regard to its pegfilgrastim biosimilar application, filed in 2015.

Stanton R. Mehr

Ritumixab Biosimilar Demonstrates Positive Results in Rheumatoid Arthritis

Breaking News: US Asks Supreme Court to Rule on Biosimilar Patent Dance

The Foundation for Building a Clinician's Confidence Over a Biosimilar Drug

Novartis: New Study on Pegfilgrastim Biosimilar Requested by FDA