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. biosimilar trastuzumab approvalIn 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.

Pfizer Gets Green Light From the FDA on Epogen® Biosimilar

It has taken a long time, but Pfizer finally earned approval from the U.S. Food and Drug Administration (FDA) on the first biosimilar version of Epogen®. The drug, Retacrit® (epoetin alfa-epbx), had originally been submitted for approval in December 2014. Its much stalled road to approval is finally at an end.

After an initial rejection, the FDA’s Advisory Committee voted overwhelmingly (14–1) in May 2017 to give the product a green light. However, the FDA changed the traffic light to red, issued a second complete response letter in June 2017, citing issues with its manufacturing plant in McPherson, Kansas (a plant Pfizer inherited with its acquisition of Hospira).

Retacrit is approved for the treatment of anemia caused by chemotherapy or chronic kidney disease, for use in patients taking zidovudine for the treatment of HIV infection, and to reduce the need for red-cell blood transfusions before, during, or after surgery.

This is the 10th biosimilar approved by the FDA, and Pfizer is expected to shortly launch only the fourth biosimilar agent. Epogen’s patent has long expired, and it was one of the first biosimilars approved in Europe (in 2007). Retacrit has been marketed in the EU for over 10 years. It is one of four biosimilar epoetin products available overseas.

In other biosimilar news… Mylan’s earnings call on May 9 produced little clarity on the fate of its upcoming FDA decision on its pegfilgrastim biosimilar. Although CEO Heather Bresch believes that its product will represent one of its most important launches of the year, she could not shed any light on partner Biocon’s response to the FDA’s critical review of its manufacturing facility. The PDUFA date is June 4; a positive decision means that Mylan/Biocon will have beaten the competition to the market for this important biosimilar product.

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.

Teva and Celltrion Receive Rejections on Trastuzumab and Rituximab Biosimilars

Celltrion and its partner Teva were dealt a significant blow today, as the Korean manufacturer announced that the latest two biosimilar candidates were rejected by the Food and Drug Administration (FDA).

Celltrion logo1As first reported by Dan Stanton in the Biopharma Reporter, the FDA issued complete response letters as a result of inspection problems uncovered at Celltrion’s manufacturing facility in Incheon, Korea. Celltrion initially receive the negative inspection report in January of this year, which highlighted deficiencies in aseptic practices and processing, and failure to investigate variations in batches.Teva

Under the partners’ pact, signed in 2016, Teva would commercialize the two biosimilars. Teva has a separate concern, however, in that the same Celltrion plant cited by the FDA has been tabbed to produce its CGRP-inhibitor fremanezumab for migraine prevention. This migraine prevention antibody, which also has the potential to reach sales of $1 billion, has a PDUFA date of mid-June.

In a statement published by Mr. Stanton, a Celltrion spokesperson said, “Celltrion is making progress addressing the concerns raised by the FDA in a Warning Letter issued in January and is committed to working with the agency to fully resolve all outstanding issues with the highest priority and urgency.”

The issuance of the CRLs may be extremely poor timing for the partners. Although Mylan signed an agreement with Roche to delay the launch of its approved biosimilar version of Herceptin® until at least 2019, the other competitors have not. Amgen/Allergan expect word on their 351(k) submission within the month, and Samsung Bioepis should hear in the fourth quarter. On the rituximab front, Sandoz should receive word early in the third quarter.

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).

FDA Rejects Sandoz Pegfilgrastim Biosimilar

In a stealthy move, Novartis released negative news within the bowels of a July 19th earnings report. Its subsidiary, Sandoz, received a complete response letter from the Food and Drug Administration (FDA) regarding its pegfilgrastim biosimilar application. A complete response letter is FDA’s euphemism for a formal rejection.

Sandoz is seeking to introduce its pegfilgrastim biosimilar as a competitor to Neulasta®, Amgen’s innovator product, which is indicated to prevent the development of infection in patients receiving cancer chemotherapy.

Novartis provided the news, buried as the last bullet under a section titled “Results from important clinical trials and other highlights.” The bullet reads, “Sandoz received a complete response letter from the FDA for biosimilar pegfilgrastim candidate (Neulasta®). We are working with the agency to address remaining questions.” A complete response letter means that based on the current data available, the agency has decided not to approve the drug for marketing.

Ed Silverman, an industry journalist, believes that Sandoz was issued the complete response letter in June. Unlike what you might think, FDA complete response letters are not released by the agency.

Sandoz first submitted its 351(k) filing on November 18, 2015 (https://biosimilarsrr.com/us-biosimilar-filings/). Ordinarily, an FDA Advisory Committee meeting would be scheduled to evaluate the product, but this did not happen. With other new drug filings, it sometimes means that FDA believes the original filing is missing data or clinical study information before it is ready to move forward.