Tag: Coherus

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.

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.

Neulasta OnproAt 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.

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.

Coherus Readying to Resubmit Its Pegfilgrastim Application

News about Coherus Biosciences has been limited since the Food and Drug Administration (FDA) rejected its initial application for a pegfilgrastim biosimilar last June. However, at this year’s JP Morgan Healthcare Conference in San Francisco, Coherus issued some positive signs of progress.

According to Dennis Lanfear, Chief Executive Officer, the company is getting ready to resubmit its 351(k) application for pegfilgrastim (CHS-1701). The FDA had cited worries about immunogenicity of the agent and specifically with Coherus’ assay to evaluate immunogenicity in its complete response letter, along with potential manufacturing plant problems.

Mr. Lanfear believes that resubmission in the first quarter of this year will yield an FDA decision before the fourth quarter. In addition, Coherus is hoping to receive European Medicines Agency marketing approval prior to this timeframe.

Coherus still has other prospects in the biosimilar arena: Its version of adalimumab is subject to patent litigation (of course), but it should receive a decision on its inter parties review motion regarding its etanercept biosimilar in March of this year.

These would be very hopeful signs after the company’s poor fortunes in 2016 and 2017. It lost its marketing partner in Baxalta (then Shire), and after receiving the FDA rejection on pegfilgrastim last year, it had cut its workforce by 30%.

The FDA Rejects Mylan/Biocon’s Pegfilgrastim; Market Still Awaits a Biosimilar for Neulasta

In the latest blow to those seeking an alternative to Amgen’s Neulasta®, the Food and Drug Administration (FDA) sent a complete response letter to Biocon, citing manufacturing plant deficiencies, in its rejection of their biosimilar pegfilgrastim application.

Announced on October 10, this is the second biosimilar from Indian manufacturer Biocon that has been detoured by manufacturing plant problems. Its Bangalore plant, where the partners’ biosimilar trastuzumab was to be manufactured, was also cited earlier this year.

In August, Biocon and its marketing partner Mylan withdrew its European Medicines Agency applications for pegfilgrastim and trastuzumab after receiving negative reports on its manufacturing facility.

This is the second FDA biosimilar rejection relating to plant deficiencies. In June, the agency issued a complete response letter to Pfizer, resulting from a legacy Hospira plant in Kansas.

In the press release announcing the latest setback to its pegfilgrastim biosimilar, Biocon said that the complete response letter relates to “facility requalification activities post recent plant modifications. The CRL did not raise any questions on biosimilarity, pharmacokinetic/pharmacodynamic data, clinical data or immunogenicity.”

Biocon also stated that “We do not expect this [complete response letter] to impact the commercial launch timing of biosimilar pegfilgrastim in the US.” Although Mylan and Biocon had not publicly announced an intended launch date once it received approval, Amgen’s principal patents for Neulasta have expired. One might have expected a relatively quick launch of its biosimilar, considering the 180-day postlaunch exclusivity period no longer exists and the possibility of other players in the market, including Coherus, Pfizer, and Apotex (all of whom received complete response letters).

Biosimilar Rituximab Under FDA Review

Celltrion announced June 30, 2017 that it has submitted its 351(k) application to the Food and Drug Administration for approval of its biosimilar version of rituximab. This represents the first biosimilar application for rituximab, a monoclonal antibody to CD20.

The product, known during investigations as CT-P10, was approved in the European Union in February, and has been launched there as Truxima in late April. Clinical data have been presented on this biosimilar’s efficacy and safety in treating rheumatoid arthritis and advanced follicular lymphoma, a form of non-Hodgkin lymphoma

If approved, Celltrion will market this product with Teva in North America, which signed a partnership agreement with Celltrion in October 2016 for this biosimilar agent to treat cancer and for CT-P6 (trastuzumab). The FDA application for trastuzumab is expected to be filed this summer. It is currently partnered with Pfizer to market its product Inflectra® (infliximab-dyyb) in the US and Canada.

Also in June, Sandoz received approval from the European Medicines Agency to market its own version of rituximab, called Rixathon™.

In other biosimilar news…Coherus Biosciences, which took hits from the FDA and its investors in the rejection of its pegfilgrastim biosimilar in June, laid off 51 workers (about 30% of its workforce) in an effort to cut costs. Coherus is working towards addressing the issues outlined in FDA’s Complete Response Letter on pegfilgrastim. In its letter, FDA did not require additional clinical studies. In the meantime, Coherus still is seeking to file its biosimilar etanercept for approval in Europe later this year, and its version of adalimumab in the US in early 2018. However, John Carroll reported that Coherus’ clinical development partner on etanercept in Japan, Daiichi Sankyo, has decided to pull out because of concerns that Coherus will not be able to manufacture the product.

Pegfilgrastim: 0 for 3 on Biosimilars at FDA

On June 12, Coherus Biosciences received word of the Food and Drug Administration’s (FDA’s) rejection of its biosimilar pegfilgrastim. Manufacturers have now taken 3 swings and misses, striking out in their quest for a biosimilar version of another blockbuster product.

In 2016, Sandoz whiffed on its version, after having the nonpegylated version approved in 2015 (Zarxio®). Although details of the FDA’s complete response letter were not released, Sandoz decided to withdraw its application to the European Medicines Agency as well. In December 2014, Apotex was the first to submit its pegfilgrastim application to the FDA, but it was similarly rejected.

The remaining biosimilar version of Neulasta® awaiting its turn at bat in the US is from Mylan/Biocon. Submitted in February of this year, the FDA decision is due October 9, 2017. Pfizer is working on its own version of pegfilgrastim (HSP-130), which is in phase 2 study. Apotex’s Apobiologix unit is still seeking approval of its biosimilar, according to its website. In Europe, 2 pegfilgrastim applications are currently awaiting decisions, but none have been approved to date.Image result for pegfilgrastim (neulasta)

On the bright side, the FDA’s complete response letter to Coherus did not indicate that the game is over. Apparently, the agency asked for a re-analysis of specific data and requested further information regarding manufacturing its biosimilar agent. The drug maker indicated its willingness to work with FDA to resolve these concerns.

There seems to be something about the pegylated version of filgrastim that makes it more difficult to obtain an approval during the first plate appearance. It may well be that Mylan’s application hits it out of the park in October. However, the batting average of drug makers pitching their other biosimilars is far better—Pfizer’s second try at approving epoetin seems to have been a hit (with a 14-1 margin by the FDA Advisory Committee).

With $4.5 billion in US sales of Neulasta last year, there will be no shortage of hitters willing to come to the plate.