A Profile on Lesser-Known Player in the Biosimilar Space: Formycon AG

On occasion, we profile some biosimilar manufacturers about whom our readers may not be as familiar as the large players like Sandoz, Amgen, and Pfizer. This generally refers to companies that have products that are in earlier-stage research or those who simply have not been in the news as often as their colleagues. In this updated post, we highlight a German company, Formycon AG, which has eyes on the US marketplace.

Formycon acquired Scil Technology GmbH in 2012, and hired a new CEO the following year. Carsten Brockmeyer, PhD, has extensive experience in the biosimilar field, previously helping Hexal Biotech to develop EPO and filgrastim biosimilars for the European market.

Why you may be hearing more about this company: Formycon has two principal biosimilar targets, ranibizumab and ustekinumab. The company disclosed that “it successfully completed a Type IV pre-submission meeting with the US Food and Drug Administration (FDA) in December 2018 and clarified other pivotal issues. The filing with the FDA for the approval of FYB201 is expected at the beginning of the fourth quarter of this year.” A filing for the European Medicines Agency is planned for 2020. A phase 3 clinical trial of this agent was completed in June 2018. In the development of this agent, Formycon partnered with Bioeq GmbH, but it is unclear whether a marketing partner exists for a possible US launch.

The patent for ustekinumab (Stelara®) expires in 2023 (US) and 2024 (Europe). It is partnered with Aristo Pharma GmbH on the manufacture and testing of this interleukin 12/23 inhibitor (also known as FYB 202).

Formycon is in the early stages of developing a phase 3 trial for its biosimilar version of Eylea® (aflibercept or FYB 203), the next generation of macular degeneration treatment. It is partnered with Santo Holding GmbH on the development of aflibercept.

In other biosimilar news… Amgen decided to pull its EMA application for its infliximab biosimilar, likely due to market competition. The company has not taken similar action with regard to an FDA application for the same product, ABP 710. Considering that neither Samsung Bioepis or Pfizer failed to gain traction in the US marketplace for infliximab, Amgen must think that some biosimilar infliximab marketshare growth in the US is still possible.

A Profile of a Lesser-Known Player in the Biosimilar Space: Bio-Thera Solutions

On occasion, we profile some biosimilar manufacturers about whom our readers may not be familiar. This generally refers to companies that have products that are in earlier-stage research or those who simply have not been in the news as often as their colleagues. In this post, we highlight a Guangzhou, China–based company, Bio-Thera Solutions.

Established in 2003, Bio-Thera Solutions “is dedicated to researching and developing innovative and biosimilar therapeutics for the treatment of cancers, autoimmune, cardiovascular diseases, and other serious medical conditions.” It claims several biosimilar and innovative therapies in its pipeline. According to its website, Bio-Thera’s leadership team members spent extensive time in the US. The CEO and Founder Shengfeng Li was also a founder of a California company Abmaxis, which was acquired by Merck, and worked at COR Therapeutics, which became part of Milennium. Chief Medical Officer Li Zhang worked for eight years at the Food and Drug Administration’s Center of Drug Evaluation and Research.  

Why you may be hearing more about this company: Bio-Thera has advanced one of its key molecules, a biosimilar of bevacizumab (reference product, Avastin®) into a phase 3 study against EU-licensed Avastin. The company’s objective is to file a 351(k) application for this product, BAT-1706, with the US FDA and the European Medicines Agency in 2020.

The company announced a new partnership with Mumbai, India-based Cipla Ltd, to market this product in emerging markets. It is not yet known whether Bio-Thera intends to partner with another organization to market in North America or attempt to build its own sales structure.

Other products in research and development include an adalimumab biosimilar (BAT-1406), for which an application for approval has been filed for the Chinese market, and a phase 1 tocilizumab (Actemra®) biosimilar (BAT-1806) for the treatment of autoimmune diseases. The company’s information does not indicate whether either of these products will be targeted for the US market. In a 2018 press release, Bio-Thera indicated that biosimilars of secukinumab (Cosentyx®), golimumab (Simponi®), and ustekinumab (Stelara®) were also in the pipeline. Regardless of the success of its bevacizumab and adalimumab biosimilars, the company seems to be well-aligned to address patent expirations of next-generation biologics.

In other biosimilar news… Regulatory Focus reported Pfizer’s announcement that the drug maker has reevaluated its biosimilar drug pipeline. It has dropped plans to develop 5 biosimilars in preclinical development. The products themselves were not disclosed and were not listed in earlier available version of Pfizer’s drug pipeline. Five other biosimilars in clinical development will continue moving forward, according to the company. This does not affect biosimilars already approved by the FDA. No reason for the decision was given, other than that this was part of an “R&E investment review.”

Predicting Coverage Changes in the Psoriasis Field: Will Biosimilars Play a Significant Role?

If you haven’t noticed, there is a good bit of action occurring on the plaque psoriasis treatment front. One long-used anti-TNF drug (Cimzia®) may be nearing approval of its  psoriasis indication, one new interleukin drug was recently approved (brodalumab), and another interleukin inhibitor is being considered by the U.S. Food and Drug Administration for approval later this year (guselkumab).

The general idea that the interleukin inhibitors have superior efficacy to the anti-TNF agents is becoming more accepted, but this is rarely reflected in the formulary preferences of health plans and insurers. Typically, these plans prefer both adalimumab (Humira®) and etanercept (Enbrel®). As with most therapeutic classes, this is the result of marketshare and net cost. AbbVie maintains the number 1 position, meaning that forcing a change or encouraging the use of an alternative preferred product is more difficult—moving significant marketshare to another agent will take considerable resources, and competitors’ pricing may not justify this battle.

Image result for Psoriasis Activity Severity Index

There is evidence that etanercept is not the most efficacious of the anti-TNF inhibitors for the treatment of moderate-to-severe psoriasis, but few health plans manage the autoimmune category by specific indication (other than arming themselves with the usual prior authorization criteria). For instance, it may be a stretch to assume that FDA approval of a new psoriasis indication for a covered biologic will suddenly force plans to change its formulary positioning of the product.

Assuming that the interleukins do represent a better chance for complete resolution of plaque psoriasis symptoms (i.e., PASI 100 vs. PASI 75), albeit at a higher net cost, it means that biosimilars for etanercept or adalimumab won’t change the clinical outlook for patients. For example, a new study announced at this week’s American Association of Dermatology meetings found that Lilly’s interleukin-17A inhibitor ixekizumab (Talz®) beat Janssen’s interleukin-12/23 inhibitor ustekinumab (Stelara®) in a head-to-head trial. The point is that anti-TNFs cannot match this level of efficacy (based on PASI scores): 83% of those treated with the interleukin-17A product achieved PASI 90 scores compared with 59% of those treated with the comparator; 49% of those treated with interleukin-17A achieved PASI 100 scores compared with 23% of those treated with the interleukin-12/23 inhibitor.

Yet health plans have not decided that the clinical benefits of the interleukins outweigh their higher costs, making them preferred products or available as first-line biologic agents. Marketshare and price are the usual sticking points.

Furthermore, the basic problem of biosimilar pricing still remains. In personal correspondence with several health plan pharmacy directors, the 15% discount offered for Pfizer’s Inflectra®, the only biosimilar anti-TNF available, is easily matched by Janssen for its Remicade® originator. Health plans could actually wind up paying more for an aggressive campaign to replace the originator brand with the biosimilar at current pricing.

This will certainly play a role in deciding whether Enbrel® can be knocked off its preferred positioning perch. With billions of dollars in annual revenue at stake, Amgen will surely take measures to match any modest discount from Sandoz on biosimilar etanercept (or at least get closer to that net-cost neighborhood with increased rebates). This may well be all that is needed to discourage biosimilar uptake on drug formularies.