Who Are the Key Lucentis Biosimilar Players to Watch?

Roche’s reference product Lucentis® (ranibizumab) seems to be the next likely target for biosimilar competition. Sales of the drug in the US were last reported to be $1.5 billion in 2017, but Roche’s revenues from Lucentis are expected to slip, owing to competition from Eylea® (aflibercept) primarily and some newer agents. And new Lucentis biosimilars will hasten that decline.

ranibizumab biosimilars

Ranibizumab is approved for use for several ophthalmologic indications, including wet age-related macular degeneration, diabetic retinopathy and diabetic macular edema, myopic choroidal neovascularization, and macular edema following retinal vein occlusion.

According to reporting by the UK-based Generics and Biosimilar Initiative (GaBI), the patents on Lucentis will expire in the US in June 2020 and in Europe in 2022. GaBI had found some 10 organizations or partnerships working on investigational ranibizumab biosimilars, but little updated information (some were reported as early as 2015).

Today, our research into the Lucentis biosimilar space revealed just a couple of active players, but with rapidly advancing plans. Here are the three initiatives reported publicly:

1. Coherus-Bioeq

This one is a little complex—stick with it, as it could be the first to obtain FDA approval, as early as later this year.

Formycon AG, a German manufacturer, gave Bioeq IP AG exclusive global commercialization rights to FYB201, Formycon’s ranibizumab biosimilar. In November 2019, with Formycon’s assent, Bioeq signed an agreement with Coherus Biosciences to commercialize the biosimilar in the US.

At the recent JP Morgan investor conference, Coherus President Denny Lanfear disclosed that Bioeq filed for FDA approval in December 2019. Coherus is expecting FDA acceptance of the application shortly, and a fourth quarter 2020 decision. This could set up a product launch, according to Coherus, in 2021.

Interestingly, Coherus originally had a different biosimilar ranibizumab in its own pipeline. This agent, CHS-3351, fell by the wayside a couple of years ago. The deal with Bioeq seems to have created a new ranibizumab opportunity for Coherus.

2. Xbrane-Stada Arzneimittel

Sweden-based Xbrane signed an agreement with the German generics manufacturer Stada Arzneimittel to co-develop Xbrane’s Lucentis biosimilar. This agent, currently dubbed Xlucane™, is being tested in a phase 3 trial involving 580 patients with age-related macular degeneration, which is slated for completion in February 2021 (interim results available in May 2020).

3. Biogen-Samsung Bioepis

Samsung Bioepis completed its phase 3 trial of SB11 in December 2019 (primary completion date of May 2019). This trial comprised 705 patients with neovascular age-related macular degeneration. SB11 seems poised to be submitted for approval via the 351(k) biosimilar pathway, and Samsung’s deal with Biogen (already a part owner of the joint venture with Samsung Biologics) for commercialization. Therefore, Biogen will take the marketing reins once an FDA decision has been given. If Samsung submits its filing in Q2 2020, a launch could be possible in Q2 2021, assuming a positive decision.

Are There Any Other Active Players Out There?

The development of PF582 by Pfenex has been on hold since 2018, after the company was handed back the full rights to the agent by former partner Hospira. Pfenex no longer lists this product (or any other biosimilar for that matter) on its pipeline. The drug had progressed through phase 1/2 studies, but has not advanced.

None of the other significant players in the biosimilar industry (including Pfizer, Sandoz, Mylan, Amgen, Celltrion, or Biocon) have publicly announced a ranibizumab biosimilar program at present.

A US–China Partnership: Coherus Biosciences Will Market Chinese Biosimilar Maker’s Avastin Biosimilar in North America

Innovent Biologics (Suzhou) Co., Ltd., based in China, signed an agreement on January 13, 2020 that allows Coherus Biosciences to commercialize its bevacizumab biosimilar when approved by Canadian and American regulators. The investigational agent is known as IB1305 at present.

Coherus

Recently completing a phase 3 trial with Chinese patients, Innovent will need to gather the necessarily analytic comparison data for US approval. In its press release, Coherus believes that an FDA submission could be possible in late 2020 or early 2021, based on the Chinese data.

Innovent Biologics

A phase 1 study was listed in ClinicalTrials.gov, which had an estimated completion date of 2017, but there has not been an update to this information. Coherus stated that “The Company anticipates completing a single dose pharmacokinetic clinical study and certain analytical/bioanalytical exercises to support the U.S. filing.” This could mean that a new phase 1 study will be undertaken. Coherus also indicated that it will handle the biologic licensing application process in the US and subsequent marketing in the US and Canada.

Additionally, the press release announced that Innovent’s biosimilar rituximab candidate (IB1301) may also be part of this deal. In June 2019, Innovent filed for approval with the Chinese drug regulatory authorities. According to the terms of the agreement, Coherus has an option to commercialize this agent in North America. IB1301 has been subject to oncology testing in China patients (not to treat autoimmune disorders).

This agreement is significant for Coherus, which is trying to build upon its success in launching the pegfilgrastim biosimilar Udenyca® in the US. Innovent’s biosimilars represent a new oncology pipeline for Coherus in the US and Canada, which already includes two anti-TNF inhibitors (adalimumab and etanercept), and two ophthalmology biosimilars (although aflibercept is still in preclinical development).

Samsung Bioepis Signals a Settlement With Genentech on Herceptin Biosimilar

And then there was one. Samsung Bioepis and Genentech filed a motion in District Court to drop all pending patent litigation regarding Ontruzant®, an approved Herceptin® biosimilar. A Joint Stipulation of Dismissal is usually the confirmation that a licensing agreement has been reached.

This leaves one remaining approved trastuzumab biosimilar maker that has not settled with Genentech (a subsidiary of Roche). Amgen’s product Kanjinti®, which was the last trastuzumab biosimilar approved (in June), is the last of 5 approved agents that is not yet subject to a Genentech agreement. The other manufacturers, Mylan/Biocon, Teva/Celltrion, Pfizer, and now Samsung Bioepis, will likely pay a royalty to Genentech whenever their products are launched.

Launch dates have not been announced (nor have the terms of these agreements) for any Herceptin biosimilar. However, the principal patent for Herceptin® has expired, so biosimilar competition should be available before the end of the year.

In other biosimilar news…Coherus Biosciences announced that it has manufactured its 400,000th dose of its pegfilgrastim biosimilar Udenyca®. Additionally, its unaudited second quarter earnings seem to indicate positive movement, as much as $84 million (more than doubling first-quarter earnings of $37 million).

More Adalimumab News: Abbvie Signs a Licensing Deal With Coherus, Coherus Sues Amgen for Patent Infringement

The multitude of companies that have lined up to sign 2023 licensing agreements with Abbvie on sales of Humira® biosimilars has grown again. The latest biosimilar maker added to the list is Coherus Biosciences.

Coherus adalimumab biosimilar

Coherus has an investigational adalimumab biosimilar that completed a phase 3 trial in 2017 in patients with plaque psoriasis and psoriatic arthritis. CHS-1420 was found to yield similar clinical outcomes compared with the reference product.

According to the press release from Coherus announcing the deal, the biosimilar will be available for marketing December 15, 2023. This will make it the eighth biosimilar version of adalimumab to enter the market, with Amgen entering first, in January of that year. As with the other deals signed by Abbvie, this signing concludes any patent litigation between the parties and Coherus will pay royalties to Abbvie on the sales of its biosimilar.

Coherus is expected to file a submission with the European Medicines Agency, though the timing of this filing has not been disclosed. Furthermore, it has not yet signed a deal with a marketing partner. In past conference calls, the biosimilar maker has indicated that it will not focus its resources on sales of its products outside the US.  

COHERUS SUES AMGEN OVER ADALIMUMAB PATENTS

To complicate matters a bit more, Coherus has launched a patent infringement suit against Amgen, believed to be the first of a biosimilar maker against another. Amgen’s Amjevita® was approved by the Food and Drug Administration in 2016, and has been for sale in the EU. Coherus intends to file for FDA approval in Q4 2019. Coherus contends that Amgen’s manufacture of Amjevita violates Coherus’ US patents 10,155,039; 10,159,732; and 10,159,733. These patents involve the creation of stable aqueous formulations of adalimumab.

Coherus seeks “damages adequate to compensate for past, present, and future infringement,” which could have implications for revenues from the European sales of Amgen’s biosimilar, because of its manufacture in the US. In addition, Coherus seeks an injunction from the court that permanently enjoins Amgen from engaging in further alleged infringement.  

Coherus President and CEO Denny Lanfear said in its January 25th press release, “Coherus recognized early on the central role intellectual property would play in advancing biosimilars to market. One important element of our IP strategy for advancing [CHS-1420] is reflected in the success we’ve achieved in patenting our innovations in the field of adalimumab formulation. We believe in the strength of our IP and we intend to protect it.”

Although generic manufacturers engaging in patent suits with competitors has occasionally occurred, this may be a first in the biosimilar community. I suppose it was only a matter of time.

More Details on Coherus Bioscience’s Udenyca Launch

Go big or go home, seems to be the message of Coherus’ President Dennis Lanfear. At the JP Morgan Investor Conference yesterday in San Francisco, he outlined what he considers a “full-on branded launch” for the biosimilar maker’s key product. Udenyca was officially launched on January 3.

In preparation for the launch of Udenyca, Coherus Bioscience secured $75 million in financing to shore up its cash position and to support its marketing effort.

Udenyca launch

The First Payer Deal for Udenyca

More than half of the current pegfilgrastim claims are reimbursed by commercial payers, with Medicare accounting for an additional one-third. Mr. Lanfear announced a couple of important payer developments that should benefit sales immediately. He said that Coherus “inked a deal with Anthem Blue Cross Blue Shield last week,” but did not elaborate on the terms. Although he alluded to a press release on Coherus’ website, none had been posted at the time of this writing. He also mentioned that Aetna and Blue Cross Blue Shield of South Carolina had independently begun “requesting Neulasta users to step through Fulphila or Udenyca before filling those claims.”

The group purchasing organization (GPO) market “is highly focused,” said Mr. Lanfear. “About a dozen players account for 95% of the market. 340B hospitals represents around $963 billion in annual revenue. Vizient accounted for $824 million in Neulasta sales last year (about 35% of the non-340B market), and welcomed us to the market.”

Targeting the Greatest Pegfilgrastim Market Opportunities

He believes, “Biosimilars with pass-through status can provide significant value in non-340B settings. They may be the lowest price side of the market, but most motivated.” According to Mr. Lanfear, these facilities’ efforts at cost recovery is expected to drive the market.

Udenyca and Fulphila are priced identically at $4,175 or at a 33% discount to Neulasta Udenyca’s 33% WAC discount per syringe to avoid payer disincentives. Specifically, after discounting and rebates, Amgen’s ASP for Neulasta was $4,422, which gives the payer an immediate ASP discount. In previous biosimilar launches, their manufacturers’ smaller discounts had actually resulted in higher ASP costs than the reference product. In those cases, payers were reluctant to encourage biosimilar use, at least until the biosimilar had sufficient time in the marketplace where its own ASP could be calculated. “Having our unique HCPCS code results in an ability to control our own ASP,” said Mr. Lanfear. This is the direct result of the current administration’s efforts to fix the original J-code rule.

Further, he believes that Coherus can take advantage of Udenyca’s reimbursement opportunity in the buy-and-bill sector. At present, Neulasta is reimbursed at ASP – 22.5%. [Non-340b] pass-through status will be designated in April 1, 2019, and Udenyca will be reimbursed at ASP + 6% for at least 2 years from that date. (Fulphila currently has pass-through status). This prevents biosimilars from being disadvantaged from the provider perspective.

A National and Regional Sales Structure

To support the new launch, Coherus has created a formidable sales force and structure, including:

  • 67 Oncology account managers
  • 7 Regional sales directors
  • 7 Key account directors
  • 7 Field reimbursement specialists
  • 7 Medical science liaisons
  • 3 Group purchasing directors
  • 4 Payer directors

Mr. Lanfear believes that creation of this extensive sales organization has not been done before with a biosimilar. And he emphasized that they expect to leverage this salesforce infrastructure for its pipeline products, including biosimilar adalimumab, biosimilar ranibizumab, biosimilar aflibercept, and a small-molecule treatment for nonalcoholic steatohepatitis (NASH).

Coherus has ramped up its production, to be able to handle demand from all its customers, and it has used the LASH Group to develop the Coherus COMPLETE support site for patients and providers.

Coherus’ plan for a “branded-type” launch for its biosimilar pegfilgrastim seems to afford benefits in pricing, sales, supply, and services. We await news of their progress.

Udenyca to Launch January 3, Same WAC as Mylan’s Fulphila

Coherus Biosciences surprised many on its third-quarter earnings call late yesterday. It will rely not on a lower price than its biosimilar competitor to gain marketshare after Coherus’ Udenyca launch, but on its ability to pull through on its patient and provider services and supply chain to gain significant marketshare for its biosimilar version of Neulasta®.

This is not to imply that Coherus will not offer contracts to group purchasing organizations (GPOs), hospitals, and payers.  The company intends to do so. However, the wholesale acquisition cost (WAC) for Udenyca® will match that of Mylan’s Fulphila®—$4,175 per vial, or a 33% discount from Amgen’s reference product. Denny Lanfear, CEO of Coherus added that the company’s contracting plans “will deliver additional value to payers.”

Jim Hassard, Coherus

AWAITING HCPCS CODING

Unlike other biosimilar manufacturers, this is their first product to reach the market. Not only was manufacturing and production a priority, but company infrastructure had to be ready for launch. Although Coherus pointed out that the sales force for Coherus is fully in place, they are holding back the Udenyca launch until the Center for Medicare and Medicaid Services (CMS) designates a Q code for claims and billing purposes. Therefore, the goal is a Udenyca launch date of January 3, 2019.

Jim Hassard, Vice President for Marketing and Market Access, emphasized that “Our overall launch strategy goes beyond pricing, to reliable supply and services. We’re committed to world-class execution and salesforce effectiveness.” The company’s Coherus Complete, patient and provider service site, is operational, and this will include copay support for eligible patients. Mr. Hassard stated, “This price is attractive to payers without diminishing our value proposition. We can deliver significant savings to the health system versus Neulasta.”Coherus Biosciences

CAN UDENYCA GRAB SOME ONPRO MARKETSHARE?

One interesting statement made during the call was the expectation that Coherus will go after some of Neulasta Onpro’s share of the market. Amgen’s on-body injector accounts for about 60% of all Neulasta utilization today, “but this growth has flattened out,” Chris Thompson, Vice President of Sales, emphasized. “We’re looking at the whole market, not just prefilled syringe market,” he said. “We think we’ll be able to sell through the Onpro market,” meaning that their pricing and services will attract some of this marketshare. In fact, Coherus executives believe that biosimilars may eventually garner nearly 70% of the pegfilgrastim market.

Coherus believes that there is pent-up demand for the biosimilar in the hospital segment today, which is why GPOs may represent promising contracting opportunities. They are seeking parity positioning at the payer and pharmacy benefit manager level.

This sounds fairly reasonable. Yet the vast majority of biosimilar consultants and payers with whom I had communicated had anticipated that Coherus would launch with at least a modest WAC discount relative to Mylan’s Fulphila. On the conference call, the investment banking participants wanting information on the Udenyca launch seemed caught off guard as well.

UDENYCA REVENUE TO SUPPORT COHERUS FOR NOW

Perhaps this strategy gives Coherus ample room for contracting while retaining a respectable net cost. Mr. Thompson said, “We’ll roll out a comprehensive contracting strategy for GPOs in the next week or two. It will be competitive and designed to win.”

It may need to be. Relying on better services and perhaps even a better supply chain (albeit one that is brand new) may not be sufficiently persuasive to hospital and payer P&T Committees. And Coherus needs to generate revenue from its sole product to feed its new sales team, new product development, and hungry investors.

Coherus Gets FDA Approval for Its Pegfilgrastim Biosimilar

With the Food and Drug Administration (FDA) approval today of Coherus Bioscience’s Udenyca™ (pegfilgrastim-cbqv), the second pegfilgrastim to compete with Amgen’s Neulasta®, much attention will be now focused on the company’s November 8 earning call.

The FDA approved Udenyca on the basis of a supportive analytical similarity package, but with phase 1 data only. Over 600 healthy subjects were given the agent to test its pharmacokinetic, pharmacodynamic, and immunogenicity safety.

We should learn a great deal by the end of the week about the nature of the competition for the injectable pegfilgrastim marketplace into 2019. In the press release announcing the approval, the company said it will reveal its launch plans, including pricing, during its week’s call. On Monday, November 5, we should hear the first information about whether Mylan’s first-to-market entry, Fulphila®, has gained some traction against the injectable form of Neulasta. Mylan launched Fulphila at the end of July.

In a previous post, we discussed how Amgen’s Neulasta Onpro® patch has already captured upwards of 80% of the pegfilgrastim business. Because of the convenience of the patch formulation, it would be surprising if Onpro’s share of market eroded significantly. However, Amgen must ensure that the net cost difference between the biosimilars and Neulasta Onpro is not noteworthy. Otherwise, payers’ can be expected to try to disadvantage Onpro through step edits or greater patient cost sharing. That would take a sizable bite out of Amgen’s large slice of the $4 billion pegfilgrastim pie.

The FDA approved Udenyca for the following indication: to decrease the incidence of infection, as manifested by febrile neutropenia, in patients with non-myeloid malignancies receiving myelosuppressive anti-cancer drugs associated with a clinically significant incidence of febrile neutropenia. It was not approved for the mobilization of peripheral blood progenitor cells for hematopoietic stem cell transplantation. This indication language does not differ from that for Fulphila. Neulasta has the additional indication of increasing survival in patients acutely exposed to myelosuppressive doses of radiation.

Undenyca was also approved for sale in the EU, although Coherus has not launched there, awaiting a marketing partner.

Coherus Biosciences Reaffirms Its Pegfilgrastim Biosimilar Hopes

Coherus Biosciences expects to have an approval decision on its pegfilgrastim biosimilar from the Food and Drug Administration by November 3, 2018. On a quarterly investor call on May 10, Chief Executive Officer Denny Lanfear also related that an approval decision from the European Medicines Agency (EMA) on this product is expected by June 28, 2018. “In the meantime, he said, we will continue building product inventory and establishing our commercial infrastructure to ensure a successful product launch.”

Biosimilars Review & Report; BR&R; pegfilgrastim biosimilarsThe conference call highlighted several notable items, including a distinct focus on the US market over the EU, primarily because of the latter’s reliance on a tender system. James Hassard, Senior Vice President, Market Access, explained that the tender system magnifies the competitive nature of biosimilar pricing. Individual countries, he said, because of their specific systems and environments can still be attractive. Mr. Hassard pointed to Scandinavia as a potential European target.

In addition, Mr. Lanfear noted that the $4 billion US market for pegfilgrastim in the US is far larger than that in Europe (< $1 billion). As a result, Coherus will likely seek a partner to help commercialize its biosimilars outside of the US, while tackling the American market itself.

The executives announced another hopeful sign for actual approval of CHS-1701—the FDA and EMA have already passed preapproval inspections of the manufacturing facilities. This could address some of the issues that have tripped up other biosimilar drug makers.

Mr. Hassard believes that Mylan will also receive approval for its delayed pegfilgrastim biosimilar around the same time as Coherus. Rather than plan for a first-to-market launch, he said they were anticipating a launch in a competitive space. “There’s a great deal of room for both us and multiple players. Our plans have always incorporated multiple players. A good example is Zarxio® and Granix®,” he said. “They’ve experienced significant success and have taken about 30% market share each.,” he said. Nonetheless, “We have plans in place to enable us to meet that level of demand even if we are the only biosimilar on the market.”

In addition, Coherus reported progress on the phase 3 clinical development of its adalimumab (CHS-1420) and etanercept (CHS-0214) biosimilars, although timing of its 351(k) submissions are not anticipated soon. The company pointed to extended patent life (adalimumab and etanercept) and lack of commercialization partners (etanercept) for delaying these filings.

Coherus Biosciences Shows Major Stock Gain Upon BLA Resubmission

When it received a June 2017 complete response letter from the Food and Drug Administration (FDA), the outlook for Coherus Biosciences was cloudy. Its lead product, a biosimilar for pegfilgrastim (CHS-1701), had been cited for the way the drug maker evaluated immunogenicity and for manufacturing plant issues. Upon receiving the news, it cut 30% of its workforce.

Furthermore, Coherus has had little luck in challenging the existing patents of originator products. It was denied inter partes review on a key patent held by Abbvie on Humira® as well as a patent on Enbrel® by Amgen.

Today, Coherus may be on the verge of a turnaround in fortunes

Armed with new immunogenicity data, Coherus resubmitted its 351(k) application with the FDA on May 3, and investors reacted strongly to its new prospects. The company’s stock price soared 17.3% for the dCoherus Biosciencesay, closing at $14.90. Its previous 52-week low was $8.05. Coherus is a U.S. manufacturer that is focused solely on biosimilar development (a “pure-play” biosimilar maker).

In the company’s announcement, Coherus reported that the new FDA application is “supported by similarity data from analytical, pharmacokinetic, pharmacodynamics, and immunogenicity studies comparing CHS-1701 and Neulasta and integrates new immunogenicity data obtained from using a more revised immunogenicity assay.” Mr. Lanfear said, “The CHS-1701 BLA resubmission marks a significant milestone in our ongoing transition to a commercial company as we tightly focus on execution of our strategic plan.”

In April, Coherus filed for a rehearing of the etanercept inter partes review.

Coherus originally filed its pegfilgrastim biosimilar application with the European Medicines Agency November 29, 2016. According to a report from early in 2018, Chief Executive Officer Denny Lanfear asserted that he hoped to receive EMA approval in the second half of 2018.

Is Physician Resistance to Biosimilars Dissipating?

We tend to think of challenges to uptake of approved and marketed biosimilars coming from three areas: (1) the reference product manufacturers, (2) the physicians, and (3) the patients. The patent mazes and rebating strategies characterize the first, and patient advocates’ questions about nonmedical switching describe the last. Physician resistance, however, seems to be on the wane.

I was pleasantly surprised by conversations with health system chief medical officers and medical group administrators speaking about biosimilar implementation and adoption at the annual meeting of the American Medical Group Association last week in Phoenix. If this is any indication, the iPhysician resistance to biosimilars decreasingnitial trepidation of US physicians in using biosimilars in treatment-naïve patients is melting away. Medical society endorsement of the effectiveness of biosimilars and promises of significant cost savings seem to be convincing arguments on physician side. Of course, switching of a reference medication for a biosimilar in a patient established on treatment with the reference product remains another story.

Some of the physicians came to learn about biosimilars rather than share their experiences. They may or may not have been aware of the extensive European experience with specific biosimilar agents and drug classes, but they were willing to accept that (1) if the Food and Drug Administration (FDA) had approved the biosimilar, they expect it to be safe and effective and (2) that extrapolation would not be an issue if FDA approved the label. The use of biosimilars for nonapproved indications would be left up to individual physicians (and payers’ prior authorization systems).

It was clear that the potential of biosimilars to save their patients money was of paramount importance. This may signal a changing view that issues regarding safety and efficacy of approved biosimilars will be preempted by the need to address economic needs in initial prescribing for new patients.

There is also an indication that large medical groups and some health systems are willing to leave the decision making to the Pharmacy and Therapeutics Committee. If the P&T Committee places the biosimilar on the formulary, and it is a savings for their new patients, the biosimilar will be used. That also means that biosimilar adoption at this level will be seriously aided by the use of lower cost-sharing tiers for biosimilars. In other words, a separate biosimilar tier that requires less copayment or coinsurance than the reference product could be a real boost to patient use.

In other biosimilar news…Michigan’s governor has signed legislation making it the 37th state to expand its pharmacy laws to allow interchangeable biosimilar substitution. Now if there were only an interchangeable biosimilar to substitute!

Coherus Biosciences announced that it believes that it will obtain FDA approval and commercial launch for its delayed pegfilgrastim biosimilar in the second half of 2018, along with European approval during the same timeframe.

Pfenex disclosed that it is seeking partners for its own pegfilgrastim biosimilar, in addition to its biosimilar candidate to Lucentis®. Its stock price has taken a steep jump in recent weeks, rising to over $6 a share (from $4) since the beginning of March.