Tag: bevacizumab

Fujifilm Gains Further Exposure in Biosimilar Partnerships

The biosimilar industry continues to make strange bedfellows. In July 2016, I reported in the Center for Biosimilars that a subsidiary of the Japanese camera maker, Fujifilm, had jumped into the biosimilar field. The Indian pharmaceutical company Biocon announced that it has launched its new insulin glargine biosimilar in Japan. Fujifilm Pharma Co, Ltd was named as the partner in this endeavor to commercialize the product in Japan.

Fujifilm Pharma is a producer of diagnostic and therapeutic radiopharmaceuticals, in addition to contrast media. This makes sense, as the parent is in the imaging business. Medical imaging can be a very natural extension of this activity. But biosimilars?

To reaffirm its strategy, Fujifilm announced a new partnership.  Its Fujifilm Kyowa Kirin Biologics subsidiary will manufacture a adalimumab biosimilar in the EU (filed for approval in the EU only) and will be commercialized by Mylan if approved. There is no information about whether Fujifilm will seek authorization to market this biosimilar in the US down the road.

Fujifilm Kyowa Kirin AstraZenecaTo further its chances of commercializing this biosimilar in the EU, Fujifilm Kyowa Kirin Biologics joined a lawsuit in April 2017 with Samsung Bioepis and its partner Biogen. The lawsuit, filed in the UK, sought to invalidate Abbvie’s two remaining adalimumab patents, and the UK court ruled in favor of the plaintiffs, opening the door to marketing next year in Europe. Fujifilm also has a bevacizumab biosimilar (FKB 238) in phase 3 clinical investigation.

The parent company has over 200 subsidiaries, and it can be complicated to track which ones are directly involved. For example, another Fujifilm company, Fujifilm Diosynth, does contract manufacturing of biologics. Yet, the phase 3 trial being carried out on FKB238 is sponsored by Centus Biotherapeutics Limited, which is a joint venture between Astra Zeneca and Fujifilm Kyowa Kirin Biologics. Centus seems to be involved only with the bevacizumab biosimilar, not with the adalimumab agent. Despite this web of intrigue, Fujifilm is not likely to be overexposed in the biosimilar marketplace. It is also unknown whether their efforts will be affected by the recent difficulties of its partners Biocon and Mylan with getting its pegfilgrastim biosimilar approved. It has been reported that Biocon will also benefit from this latest Mylan collaboration.

Amgen/Allergan Score Positive EMA Evaluation, but Launch Will Be Delayed

A couple of noteworthy pieces of news have emerged from across the pond on the biosimilar front. The first involves progress for Amgen’s application for its bevacizumab biosimilar at the European Medicines Agency (EMA). Its drug evaluation arm, the Committee for Medicinal Products for Human Use, recommended approval of the biosimilar on November 9.

Assuming EMA final approval is received, however, Amgen and Allergan’s cancer treatment agent will not be marketed any time soon. The principal European patent is not set to expire until 2022.

Image result for avastin biosimilarIn the US, Mvasi™ was approved by the Food and Drug Administration in September, but its launch is similarly delayed by patent litigation. The main US patents should expire in 2019 (Roche claims to hold 27 enforceable patents). Amgen had filed suit October 6 challenging the validity of the patents in question, but this case may not be heard until late 2018. Amgen has the option of launching “at-risk,” but it has not indicated that it will go this route. Otherwise, the earliest launch may be sometime in 2019.

Several other potential bevacizumab makers have already challenged the patents, according to other reports. These include Boehringer Ingelheim, Celltrion, Pfizer, and Samsung Bioepis.

In other related news…An announcement will be made on November 20 regarding where the EMA will relocate its headquarters as a result of the Brexit. The Agency will need to complete its move by March 31, 2019, when Britain’s divorce from the European Union is finalized.

Amgen Receives Approval for Bevacizumab Biosimilar

The Food and Drug Administration announced today the approval of the first biosimilar for Roche’s Avastin®. The approval of Mvasi™ (bevacizumab-awwb) represents the first biosimilar approved in the US for the direct treatment of cancer. Amgen is partnered with Allergan in the development and marketing of the new biosimilar.

Its approved indications include:

  • Metastatic colorectal cancer, in combination with intravenous 5-fluorouracil-based chemotherapy for first- or second-line treatment. Mvasi is not indicated for the adjuvant treatment of surgically resected colorectal cancer.
  • Metastatic colorectal cancer, in combination with fluoropyrimidine-irinotecan- or fluoropyrimidine-oxaliplatin-based chemotherapy for the second-line treatment of patients who have progressed on a first-line bevacizumab product-containing regimen. Mvasi is not indicated for the adjuvant treatment of surgically resected colorectal cancer.
  • Non-squamous non-small cell lung cancer, in combination with carboplatin and paclitaxel for first line treatment of unresectable, locally advanced, recurrent or metastatic disease.
  • Glioblastoma with progressive disease following prior therapy, based on improvement in objective response rate. No data is available demonstrating improvement in disease-related symptoms or survival with bevacizumab products.
  • Metastatic renal cell carcinoma, in combination with interferon alfa.
  • Cervical cancer that is persistent, recurrent, or metastatic, in combination with paclitaxel and cisplatin or paclitaxel and topotecan.

Like Avastin, Mvasi will carry a black box warning involving gastrointestinal perforations, surgery and wound healing problems, and severe or fatal hemorrhage.

The FDA’s Oncology Advisory Committee had unanimously recommended approval of the agent. No announcement was made by Amgen as to pricing or availability of the new product.

FDA Advisory Committee Unanimously Recommends Approval for Avastin® and Herceptin® Biosimilars

It was a good day for biosimilar manufacturers and a bad day for Roche and its Genentech unit. Following a broadly positive FDA staff review of the first products to directly treat tumors, the Food and Drug Administration’s Oncology Drug Advisory Committee took the expected step of unanimously recommending approval for agents from Amgen and Mylan.

In the morning session, Amgen and Allergan’s ABP-215 was convincingly presented as equivalent to Roche’s bevacizumab (Avastin®), based on  pharmacologic, pharmacokinetic, efficacy, and safety evaluations. Clinical studies were performed in patients with non–small cell lung cancer. The Advisory Committee voted 17-0, recommending approval of the drug for all of the originator product’s nonprotected indications:

  • As first- or second-line treatment of patients with metastatic carcinoma of the colon or rectum in combination with intravenous 5-fluorouracil-based chemotherapy
  • Combined with fluoropyrimidine-irinotecan- or fluoropyrimidine-oxaliplatin-based chemotherapy, for the second-line treatment of patients with metastatic colorectal cancer who have progressed on a first-line ABP 215-containing regimen
  • As first-line treatment of unresectable, locally advanced, recurrent or metastatic nonsquamous non–small cell lung cancer in combination with carboplatin and paclitaxel
  • For the treatment of glioblastoma with progressive disease in adult patients following previous therapy as a single agent
  • For the treatment of metastatic renal-cell carcinoma in combination with interferon alfa
  • In combination with paclitaxel and cisplatin or paclitaxel and topotecan for the treatment of persistent, recurrent, or metastatic carcinoma of the cervix

Several questions brought up by the Committee involved the glioblastoma indication, and the drug’s passage over the blood–brain barrier. Progressive multifocal leukoencephalopathy was also mentioned, but this did not deter the Committee from its unanimous vote.

Amgen did not apply for approval for Avastin’s other orphan indications, which are “protected,” according to FDA. If they did want to obtain approval for those, an additional data package would need to be submitted.

Immunogenicity studies did not reveal any material differences between the biosimilar and originator product. In a minor twist, Amgen did the clinical testing of its biosimilar against the EU-licensed version of Avastin, and it had to conduct bridging studies to demonstrate the similarity between the EU version and the US-licensed originator drug.

In the day’s second session, Mylan’s MYL-1401O, a biosimilar version of Roche’s Herceptin (trastuzumab), was evaluated. The totality of evidence, according to the FDA staff review documents, supported the 351(k) application by Mylan. The Advisory Committee agreed, voting 16-0 to recommend the biosimilar for approval for use in Herceptin’s indications:

  • For use as adjuvant treatment of HER2 overexpressing node- positive or node-negative (ER/PR negative or with one high risk feature) breast cancer (1) as part of a treatment regimen consisting of doxorubicin, cyclophosphamide, and either paclitaxel or docetaxel; (2) with docetaxel and carboplatin; or (3) as a single agent following multimodality anthracycline-based therapy
  • In combination with paclitaxel for first-line treatment of HER2-overexpressing metastatic breast cancer
  • As a single agent for treatment of HER2-overexpressing breast cancer in patients who have received one or more chemotherapy regimens for metastatic disease
  • In combination with cisplatin and capecitabine or 5- fluorouracil, for the treatment of patients with HER2 overexpressing metastatic gastric or gastroesophageal junction adenocarcinoma who have not received prior treatment for metastatic disease.

The FDA usually accepts the recommendation of its Advisory Committees in issuing final decisions. However, in late June, the agency rejected Pfizer’s Retacrit despite a 14–1 Advisory Committee vote to recommend, based on potential problems at a manufacturing facility. Mylan’s manufacturing partner Biocon, has recently been cited by French inspectors in connection with its European approval application, for potential problems at its Bangalore plant.

A final FDA decision is expected for Amgen’s bevacizumab biosimilar by September 14, and for Mylan’s trastuzumab biosimilar by September 3.

Will Oncology Biosimilars Ease US Access Problems?

Among the broad arguments for the rapid introduction of biosimilars is that they will increase patient access to expensive biologic therapies. This may be true theoretically from a patient cost-sharing perspective. If the biosimilar is priced sufficiently less than the originator product, health plans and insurers may elect to prefer the biosimilar and place it on a more affordable coinsurance or copayment tier.

This is not generally the case for the 2 nononcology biosimilar products launched to date. With shallow discounts for the biosimilars, the originator’s manufacturer can simply match the net cost through deeper rebates; the payer would have little reason to change the formulary tiering of the biologic.

The title is sort of a trick question. It assumes that there is a problem accessing oncology agents in our nation today. A 2015 study of 150 oncologists indicates that this is not the case. None of the respondents reported that obtaining Image result for Truxima imageRituxan for their oncology patients (chronic lymphocytic leukemia or non-Hodgkin’s lymphoma) was a problem. The researchers also surveyed doctors in Brazil, Mexico, Russia, and Turkey. In Russia, 12% indicated that access to Rituxan was indeed difficult, as did 17% in Turkey. The researchers also stated that Russia and Mexico, compared with the other countries included in the study, had the greatest share of patients who did not have any insurance. Of course, it must be noted that the cost of Rituxan is far less in the other countries studied, compared with the US.

Another way in which the introduction of a Rituxan biosimilar could improve access is to alleviate present or future drug shortages. Drug shortages are commonly the result of a couple of factors: manufacturing plant slowdowns or shutdowns (often related to quality issues or the need for maintenance); lack of available drug components, such as its active ingredients or excipients; lack of profit driving generic manufacturers out of the business.

According to the Food and Drug Administration, which is responsible for tracking drug supply shortages, Rituxan has not been subject to any supply notifications, nor have any of the biologicsSupply Chain. However, oncology has not been immune from drug shortages (e.g., daunorubicin liposomal injection, leucovorin injection). In a recent post, I emphasized that the need for anything less than a water-tight drug supply record can torpedo and sink biosimilar marketing efforts. In this instance, one can also make the case that oncology biosimilars like rituximab, trastuzumab, and bevacizumab could serve as a stalwart against potential biologic supply issues.

The outlook for the patient’s ability to pay for expensive medications is cloudier by the day. Access to these drugs is not an issue in the US today, but what about a year from now? How will efforts to change the pre-existing exclusion rules alter the landscape for covering any of the biologic products? Then, biosimilars may be in a real position to maintain or improve access.

The first oncology biosimilars are very close: Decisions from the Food and Drug Administration on biosimilars for trastuzumab and bevacizumab are expected in the third quarter of this year. Celltrion expects to file its 351(k) application for rituximab in June.