Mylan’s Fulphila Pegfilgrastim Biosimilar Launches at Big Discount

The first pegfilgrastim biosimilar (Fulphila™) in the US has begun marketing, and Mylan/Biocon are offering a 33% discount to the wholesale acquisition cost (WAC) of the originator product Neulasta^®. The Center for Biosimilars reported a communication from Mylan confirming the action. This is a watershed moment for the pegfilgrastim category and could signal the beginning of large savings opportunities for payers and patients.

At a WAC of $4,175 per syringe, the pegfilgrastim biosimilar may be very attractive to health plans and insurers. It is also assumed that this will effectively drive down the average sales price (ASP) of the category over time. The ASP includes the WAC as well as any rebates or discounts given by the manufacturers.

The pegfilgrastim biosimilar, like the reference drug, Amgen’s Neulasta, is approved to decrease the incidence of infection as manifested by febrile neutropenia in patients receiving myelosuppressive chemotherapy.

Although patent litigation between the partners and the maker of the originator product (Amgen), Mylan/Biocon have decided to launch at risk. This means that if the District Court sides with Amgen, Mylan’s could face large financial penalties, including profits on the sales of the biosimilar.

An FDA Filing for Momenta’s Adalimumab Biosimilar Coming Soon?

Momenta seems to be in final preparations for its first 351(k) filing to the Food and Drug Administration (FDA). In its recent investor conference, the company disclosed that it is ready to send M923, its adalimumab biosimilar, to the agency for approval.

Despite this promising news, Momenta is facing strong headwinds. Even if it gains approval, Momenta expects that the US launch of the adalimumab biosimilar will not occur until 2023, owing to pending patent issues with Abbvie’s Humira^®. The company does not yet have a marketing partner for this agent, though there appears to be plenty of time.

In addition, Momenta received a setback in November 2017 on another looming biosimilar candidate, when its biosimilar version of abatacept failed its phase 1 trial. Apparently, its M834 produced pharmacokinetic results that differed from the originator Orencia^® in this early clinical study. Momenta is still studying the data and trying to come to grips with the surprising findings.

The company is also set to begin “pivotal” clinical trials on its other drug candidate M710, a biosimilar to aflibercept. The originator product is Eylea^®, and it is indicated to treat wet age-related macular degeneration.

Momenta’s partnership with Mylan is moving forward with preclinical work on four other nonspecified biosimilars, according to the company. But all of this development costs money, and Momenta has acknowledged that it may need to raise cash for future development.

Momenta received approval in January for a generic form of the multiple sclerosis drug Copaxone^® (glatiramer acetate). The approval of this agent, produced in partnership with Sandoz, had been delayed because of manufacturing issues. The company recognizes that the entry of Mylan (ironically) into this market may hinder its financial outlook.

As a result of these developments, Momenta stated it would entertain a sale of its adalimumab biosimilar “or other assets.”

The Patent Games: Another Sequel Underway

Roche/Genentech has filed suit in Delaware, citing the alleged violation of 37 patents by Amgen in its intent to market its biosimilar version of Herceptin^®.

The litigation was filed in response to Amgen’s stated intention of launching their product in October 2018, based on a May approval. Unfortunately, the Food and Drug Administration decided not to approve Amgen and Allergan’s initial 351(k) application in early June.

Roche has been engaged with Pfizer and the team of Celltrion and Teva on their trastuzumab biosimilars as well.

Mylan and Biocon Land First Pegfilgrastim Biosimilar Approval

The race to bring a pegfilgrastim biosimilar to market officially started on December 17, 2014. The checkered flag fluttered 3½ years later on June 4, 2018, with the Mylan/Biocon team winning on a slow track. The partners earned approval from the US Food and Drug Administration (FDA), becoming the first biosimilar to challenge for this $4 billion market.

Mylan will market the product in the US, and it is assumed that the product will be launched shortly,= to take advantage of their window of opportunity. The drug will be called Fulphila™, and the FDA assigned a formal name of pegfilgrastim-jmdb. The next likely competitor, Coherus, is expected to receive word from the FDA by November 2. Mylan will have the chance to quickly grab marketshare if they produce attractive deals for payers.

FDA Approval Eludes Amgen for Biosimilar Trastuzumab

Amgen will have to wait a bit longer to market its biosimilar version of trastuzumab . On Friday, June 1, the Food and Drug Administration (FDA) rejected Amgen’s 351(k) application for its Herceptin^®biosimilar. In a brief press release, Amgen announced receiving the complete response letter for ABP 980. In the announcement, it also said that the delay in its biosimilar trastuzumab approval should not “impact our US launch plan.” This may signal that even if it received approval, it would not market the biosimilar trastuzumab immediately.

The timing of the FDA announcement on the biosimilar trastuzumab approval contrasted with the near-simultaneous marketing authorization of this same trastuzumab biosimilar by the European Medicines Agency. The biologic will be marketed in Europe under the trade name Kanjinti™.

Mylan/Biocon’s Ogivri™ remains the only biosimilar trastuzumab approved by the FDA. It is not yet marketed, however. Separate trastuzumab biosimilars by Teva/Celltrion and Pfizer have been stalled by the FDA. Samsung Bioepis’s entry is due for an FDA approval decision in the fourth quarter of 2018.

In related biosimilar news… in September 2017, Mylan filed a 505(b)2 application for its insulin glargine agent. The manufacturing duo of Mylan and Biocon received a rejection from the FDA on June 1. The complete response letter specified issues raised by a change in manufacturing site (from one in India to a new facility in Malaysia). As reported by the Economic Times, the complete response letter was expected by Mylan and Biocon. They told the Economic Times, “Together, Mylan and Biocon are already executing on all required activities we had agreed upon with the FDA, and they are progressing according to plan,” the statement said.

Although insulins are not currently approved through the 351(k) biosimilar pathway, they are among the “transitional agents,” which by 2020 will be considered biosimilars by the FDA.

What Is the Biosimilar Pegfilgrastim Market Opportunity?

We’ve covered the contest to bring a biosimilar pegfilgrastim to market, with considerable depth. The progress and setbacks of Mylan/Biocon, Coherus Biosciences, Sandoz, and Apotex have been tracked. Other drug makers are also working on plans towards 351(k) applications for approval. Eventually—likely sooner than later—one or two will hit the market.

Biosimilar Pegfilgrastim, Neulasta^®, and Onpro^®

Amgen, maker of the originator product Neulasta^®, disclosed in its first-quarter financial report that the total sales for the product in the US is $1.0 billion, $146 million for the rest of the world, for a total of $1.15 billion. This means a US market of approximately $4 billion for one year of sales. Amgen also noted that 62% of its first-quarter Neulasta sales are associated with its Onpro^® kit. Although the major patents for pegfilgrastim have expired, Onpro is still protected by patent. Onpro does have some significant advantages in that the patient does not need to go to the doctor’s office for an injection after receiving chemotherapy. The sales figures indicate that doctors prescribe it in preference to the injectable form of pegfilgrastim.

At a current 62% marketshare for Neulasta Onpro, the initial total slice of the pie available for biosimilars may only be $1.5 billion (not considering WAC discounts). If we assume a 20% discount, this may be closer to $1.2 billion. It may not seem logical for Amgen to make great efforts to defend its share of injectable pegfilgrastim because of its successful conversion to Onpro. Also, Onpro does have marketable advantages over the injectable form.

The list price of Neulasta is upwards of $7000 per injection, and Amgen does not charge additionally for the Onpro kit. This stance may prove an incentive to health plans and insurers to not encourage biosimilar use over Onpro.

Will Physicians Resist Moving From Onpro to a Biosimilar Pegfilgrastim Injection?

The $1.2 billion to $1.5 billion estimate also assumes that Amgen cannot convert more patients to Onpro prior to approval of a new biosimilar. That would further shrink the revenue opportunity. Physicians may also resist payer efforts and not prescribe the injectable form if they favor the Onpro kit. To the extent that payers may prefer the biosimilar (or otherwise restrict the use of a more expensive originator agent) when it becomes available, that slice of the pie could increase quite a bit. Furthermore, the picture could also change in a few years as biosimilar manufacturers develop delivery systems that gain the same advantages as Onpro.

In its earnings report, Amgen indicated the sales of Neulasta have been decreasing, by 5% from the same quarter last year. This may be the result of movement to other, less-toxic cancer chemotherapies or other treatments to prevent neutropenia and its related infections.

The Onpro market for the rest of the world may be given a boost soon, as Amgen also announced that the European Medicines Agency issued a positive opinion for the drug maker to include the Onpro Kit in its EU label.

As reported in BR&R, Coherus CEO Denny Lanfear thought the pegfilgrastim market may be split in a manner similar to that for filgrastim (i.e., 30%/30%/40% shares for 2 biosimilar makers and the originator). That may possibly mean 30% of a $1.2 billion US market (not $4 billion), if payers do not emphasize the use of the biosimilar over Onpro.

Trastuzumab Dosing May Be Given in Half the Time: Will Costs/Revenues Be Cut as Well?

An upcoming presentation at the annual American Society of Clinical Oncology (ASCO) meeting promises equal efficacy and much improved safety for patients with early-stage breast cancer receiving Herceptin^®. This change in trastuzumab dosing from a 12-month to a 6-month regimen will have ramifications for patients, health systems, and manufacturers.

trastuzumab biosimilar A number of biosimilar drug makers are trying to be the first to enter the market for trastuzumab. Mylan/Biocon’s Ogivri™ (trastuzumab-dkst) is the only approved agent in the US, but it will not launch before 2019, owing to a licensing agreement with Roche. Amgen/Allergan is expecting word from the Food and Drug Administration (FDA) by May 28^th on their own biosimilar version. Samsung Bioepis is also expecting a decision in the fourth quarter of this year. This new study could significantly lower anticipated revenues for these drug makers. The expected pricing pressures of the category (another 2 manufacturers are working through complete response letters from the FDA) will further add to lower revenue.

Trastuzumab Study Results: Half as Long Just as Good

This British study comprised over 4,000 women (median age, 56 yr) who were followed for more than five years. Patients were randomized to receive the originator trastuzumab for either six or 12 months, in addition to usual standard of care. The researchers found that the disease-free survival was 89.8% in the 12-month group compared with 89.4% for the 6-month group. However, the latter showed significantly fewer toxic effects of cancer therapy.

The wholesale acquisition cost for trastuzumab approaches $6,400 per month ($76,700 per 12-mo course). This may lower patients’ out-of-pocket costs, depending on how quickly they reach their cost-sharing maximums. Typically, women taking trastuzumab will be subject to a fixed copay (e.g., $300 per treatment) or a co-insurance (e.g., 20% or $1,280 per month) for this medication alone. Yet, even with the treatment duration being halved, some patients may reach their out-of-pocket maximums. This is the result of office visits, other medications to be taken, and other care related to the toxic side effects of chemotherapy.

Half the Duration but not Half the Costs

For payers and health systems, cost savings will be substantial, but not halved. Most of the costs will be incurred with the first 4 months of weekly therapy. After 12 to 18 weeks, treatments are stretched out to infusions every 3 weeks for the remainder of the regimen. For a 100-kg woman who would receive a total of 5,400 mg of trastuzumab over 52 weeks, this could be reduced to 3,666 mg over 26 weeks (–32%).

The real benefit, should these study results pass scrutiny of peer review and inclusion in practice guidelines, will be in the lower frequency of toxic adverse effects. According to its prescribing information, trastuzumab is associated with “left ventricular cardiac dysfunction, arrhythmias, hypertension, disabling 197 cardiac failure, cardiomyopathy, and cardiac death.” This can occur during therapy (causing discontinuation) or in the years after treatment is completed.

We hope that the good news represented by these study results for patients does not dissuade other manufacturers from seeking biosimilar trastuzumab approval.

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 d ay, 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.

FDA Hands Sandoz a Rejection on Its Rituximab Biosimilar

Sandoz announced today that the Food and Drug Administration (FDA) has decided not to approve its biosimilar version of the oncology biosimilar rituximab. The content of the complete response letter was not revealed by Sandoz.

This marks the second rituximab biosimilar rejected by the FDA. Celltrion and Teva’s Truxima™ was also rejected in early April. Both Sandoz’s biosimilar (Rixathon™) and Truxima™ are marketed in Europe and in other parts of the globe. In Europe, Rixathon was approved in June 2017, and Truxima received marketing authorization in February of that year.

Although the European approval for Rixathon was for all of Rituxan/MabThera’s oncology and autoimmune indications, Sandoz was seeking oncology indications only in the US with its rituximab biosimilar.

Sandoz registered early success with filgrastim (Zarxio®) and etanercept (Erelzi®), but was handed a set back from FDA on its biosimilar pegfilgrastim. We’ll report any updates we receive on Sandoz’s progress in resolving the issues in question with rituximab.

Next up is the Allergan/Amgen biosimilar of trastuzumab, which has an FDA PDUFA date of May 28.

Pfizer Receives FDA Rejection on Trastuzumab, Next up Is Amgen/Allergan

When Pfizer announced that it received a complete response letter from the Food and Drug Administration (FDA), the wait for an available biosimilar to Herceptin^® just got longer. According to the manufacturer, the FDA specified that the reasons for the rejection of PF-05280014 were not related to clinical questions. The rejection was not associated with manufacturing plant problems, which have tripped up biosimilar manufacturers, including Pfizer, in the past. Instead, the FDA cited the need for additional data related to “technical issues.”

The next potential team up at bat for a trastuzumab biosimilar approval is Amgen and Allergan. A decision on their biosimilar should be rendered before the end of the second quarter. To date, only Mylan/Biocon have obtained approval on this oncologic product (Ogivri™). However, the launch has been delayed by their signing an agreement with Roche, the maker of the reference product. Teva/Celltrion had received a rejection from FDA relating to manufacturing issues in early April, setting back their own marketing timetable.

Even if Pfizer did receive approval at this time, Roche had sued the company in November 2017 for patent infringement. Pfizer had elected to launch at risk with Inflectra^®, despite looming legal battles with Janssen over Remicade^®, so an immediate launch of their trastuzumab biosimilar could not be ruled out.

Like the situation with pegfilgrastim, gaining competition for trastuzumab is proving frustrating for payers. Obviously, it will occur, but the latest news does not alleviate payers concerns over price increases in the oncology area.

With the Samsung Bioepis Deal, Abbvie Tightening Its Grip on the US Adalimumab Market

Samsung Bioepis and Biogen has reached a deal with Abbvie that would enable it to market its biosimilar adalimumab (should it be granted approval) in June 2023. This is the second deal Abbvie has made with a potential competitor, confirming the solidity of its patent wall. The European patent expires in October 2018, and competitors will be able to sell biosimilars over the pond unhindered at that time.

However, without competition, most expect unencumbered price increases until a US biosimilar introduction. In other words, biosimilars will not make an appreciable impact on the cost of adalimumab in the US market, unless another biosimilar manufacturer decides to launch at risk in the near future.

A Deal Prior to FDA Approval

The agent, SB5 has not yet been filed for approval in the US. Samsung filed its application for approval in the EU in July 2016 and was authorized by the European Medical Agency in August 2017. Biogen will market the agent for Samsung, whenever it is launched.

Amgen inked a deal with Abbvie in September 2017, effectively ending its patent battle. This deal gives Amgen a jump on other competitors that reach settlements with Abbvie, by allowing a launch in January 2023. In addition, other manufacturers are working on adalimumab biosimilars, including Coherus and Sandoz. The biggest question though is Boehringer Ingelheim’s move, as they have the only other FDA-approved adalimumab biosimilar approved on the marketplace (but also unlaunched). Boehringer responded to our request but declined to comment on its plans m Abbvie produces Humira (adalimumab) oving forward with the product, including a targeted launch date.

Without Competition, Expect 45% Jump in WAC Price

As addressed earlier in this space, the time to effective competition for a US biosimilar adalimumab is crucial. Abbvie’s annual global revenue on the product may reach as much as $21 billion, with the last price increase registered in January, at 9.7%. Assuming Abbvie sticks to its pledge of no more than one

10% price increase per year, that would result in a wholesale acquisition cost (WAC) of more than $52,000 at the close of 2022, or a 45% jump from today’s WAC. This figure does not reflect individual negotiated rates (including rebates) that health plans and insurers actually pay. Yet, it does roughly indicate what type of discount will be necessary when biosimilars reach the market to simply attain the cost paid in 2018—that is, no more savings. Without competition before 2023, this may be the one area where payers pray for a rapid and bracing race to the bottom on price once 2023 rolls around. With Abbvie’s hand continuing on the tiller, don’t plan on it.

In other biosimilar news…Celltrion acknowledged that it is seeking to rectify the manufacturing plant issues that torpedoed its FDA approval of biosimilars for trastuzumab and rituximab. In the statement, it noted, “Celltrion is confident that the issues raised by the FDA will be resolved in a timely manner.

We can confirm that the resubmission will be in-place relatively soon. Then, we are expecting approvals in 6 months after resubmission according to regulatory timeline.”