Tag: Biocon

Sandoz and Biocon Partner on Next-Gen Biosimilars

On January 18, Sandoz and Biocon announced a new biosimilar partnership, which could extend both manufacturers’ market presence.

Although the specific biosimilar targets were not specified, the firms indicated that they will work to develop and commercialize next-generation oncology and immunology biosimilars. Unlike other partnerships that are delineated along the lines of manufacturing and marketing, this deal will be a 50/50 venture, in which Sandoz and Biocon will co-develop the agents and split marketing duties by region. Sandoz will be responsible for commercializing the drugs in North America and the EU, and Biocon will be responsible for all other economic areas.

Image result for richard francis sandoz
Richard Francis, CEO, Sandoz

“Our collaboration with Sandoz will bolster our existing global biosimilars portfolio comprising biosimilar antibodies & insulin analogs and will enable us to address the next wave of global biosimilars opportunities,” Arun Chandavarkar, CEO and Joint MD, Biocon said in India’s Business Standard.

Richard Francis, CEO, Sandoz stated, “[This agreement] bolsters our leadership position in biosimilars and positions us to continue to lead well into the future…Through this collaboration, we are reinforcing our long-term commitment to increase patient access to biologics.”

Biocon is currently involved in a partnership with Mylan, which so far resulted in the approval of a biosimilar version of trastuzumab in December 2017 (although the agent may not be launched until 2019–2020 because of an agreement Mylan reached with Roche, the manufacturer of the originator Herceptin®).

Fourth Herceptin® Biosimilar Being Evaluated by FDA

The end of 2017 has been bustling with oncology biosimilar news.

On December 20, 2017, the Food and Drug Administration (FDA) accepted Samsung Bioepis’ application for SB3, its biosimilar version of trastuzumab. The drug would be the fourth to undergo evaluation by the FDA, and may pack on the pressure for Mylan and Biocon’s product Ogivri™, which is the only approved biosimilar trastuzumab.

Mylan/Biocon’s biosimilar was approved earlier this month. As a reminder, though, there are no plans to bring their version of trastuzumab to market immediately. Indications are that Breast Cancerowing to an agreement with Roche, they may not launch until 2019 (at the earliest). Trastuzumab biosimilar entries by Celltrion and Amgen/Allergan will not receive FDA decisions until the second quarter of next year. It is unclear whether these manufacturers will decide to launch their versions at risk, thus stealing the initiative from Mylan and its partner. In any case, competition should be vigorous when these products launch (which should be within 12 months of the first launch, assuming FDA approvals). At present, the question is open as to whether Samsung will market SB3 if it receives a positive decision sometime in the fourth quarter of 2018.

In related news…A survey of 200 oncologists revealed that their comfort levels with prescribing biosimilars is widespread. Cardinal Health published a report based on the survey on December 20.

Although these result may relate to oncologists’ multiyear experience with Zarxio® (filgrastim), 82% of the oncologists responding to the survey specifically indicated that they would have no qualms about using biosimilars to treat patients with breast cancer in an adjuvant setting or if they had metastatic disease. As indicated above, no biosimilars are currently marketed for this indication. Furthermore, they expect significant cost savings when using biosimilars: Two thirds said that cost savings with biosimilars are either extremely or very important in their prescribing decision. That’s pretty much the point of biosimilars, isn’t it?

Mylan/Biocon Receive First Approval for Trastuzumab Biosimilar, but First to Market?

On December 1, the team of Mylan and Biocon received their first biosimilar approval in the US, for an agent to compete with Roche’s Herceptin®. The approval decision on this product was delayed 3 months owing to potential issues involving Biocon’s manufacturing facility. However, this marks the first biosimilar approved for trastuzumab, beating entries from Amgen/Allergan and Celltrion to the 351(k) finish line.

Dubbed Ogivri™ (trastuzumab-dkst), the Food and Drug Administration (FDA) approved the biosimilar to treat human epidermal growth factor receptor (HER)–positive (HER+) breast cancer and HER2+ metastatic stomach cancer (gastric or gastroesophageal junction adenocarcinoma). The FDA’s Oncology Drug Advisory Committee voted unanimously to approve the drug, and it was originally scheduled for a decision in early September.

Scott Gottlieb, MD, the recently installed FDA Commissioner, stated, “The FDA continues to grow the number of biosimilar approvals, helping to promote competition that can lower health care costs. This is especially important when it comes to diseases like cancer that have a high cost burden for patients. We’re committed to taking new policy steps to advance our biosimilar pathway and promote more competition for biological drugs.”

Ogivri will carry the same Boxed Warning as Herceptin, regarding increased risks of heart disease (cardiomyopathy), infusions reactions, lung damage (pulmonary toxicity) and harm to a developing fetus (embryo-fetal toxicity).

The launch of the product may be delayed until 2019 or 2020, based on an agreement between Mylan and Roche. This could mean that although Ogivri is first approved, it may not be first launched.

Fuzzy Patent Logic

Over the past week, month, year (you name it!), we’ve read too much about the trials and tribulations of patent litigation. The latest, involving Pfizer and Roche, has the latter suing Pfizer for infringing on upwards of 40 Roche patents in Pfizer’s development of a trastuzumab biosimilar. This is pretty common these days, and even the number of patents involved fails to surprise. Yet, other competitors may reach the market before Pfizer; it has not yet filed for a 351(k) approval with the Food and Drug Administration (FDA) or the European Medicines Agency.

BR&R Logo Transparent1.5-21-2017

This does not apply to other potential players. Celltrion cleared the Roche patent lawsuits in April 2017, enabling it to sell its trastuzumab biosimilar in its home country of Korea. This does not necessarily apply to sales in other countries, however.

Positive results were announced for a pivotal phase 3 study of Pfizer’s trastuzumab biosimilar PF-05280014 in Europe in September. These results will likely form the clinical backbone of its 351(k) application.

First launched in 1998, principal patent expiration of Herceptin in the US should be 2018 or 2019 and was 2014 in Europe. It may be assumed that Amgen/Allergan will wait for patent expiration before marketing their product in the US and subsist on sales in Europe in the meantime.

A similar but more protracted situation exists with Abbvie’s Humira®, for which competition will be fierce once the patents expire fully in 2023 (if they are not found to be invalid earlier). Amgen settled with Abbvie to obtain a global license from the originator’s manufacturer, applying to sales after this time. However, Amgen’s biosimilar will still have to compete with severals once the patents expire or are ruled invalid.

I’d like to post others’ opinions as to how the marketshare wars will play out when some patent agreements are made and others are not. What do you think will happen on the Herceptin front?

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).

The Week in Biosimilar News

You know it’s been a pretty desperate week in the biosimilar blogosphere when twitter feeds relate back to articles published in January, rehashes of the US Supreme Court decision in June, or yet another estimate of the savings potentially ascribed to biosimilar use (based on erroneous assumptions). However, there were a few significant tidbits announced last week that are worth reviewing.

First, Biocon announced that the decision to approve its trastuzumab biosimilar (with partner Mylan) has been delayed by the Food and Drug Administration (FDA) 3 months (until December 3, 2017). According to Biocon, this delay was required so that the FDA could “review some of the clarificatory information submitted as part of the application review process.” Clarificatory? Really? Maybe the extra time was needed to translate the application itself.

Second, a survey of 103 US gastroenterologists raised a couple of questions as to how well information about Inflectra®, the biosimilar to Remicade®, is sinking in on the practice level. According to a press release from Spherix Global Insights, cross-category prescribing may be interfering with the uptake of the biosimilar. They state, “not only is the decline [in Remicade prescriptions] attributed to the adoption of infliximab biosimilars, but use of Humira® has also significantly increased, potentially indicating that more ulcerative colitis patients are being placed on Humira to avoid insurance mandates for infliximab biosimilar use.” This limited survey found that more than one-third of gastroenterologists “agree that if a pharmacy or managed care plan advises them to use Inflectra over Remicade, that they are more likely to choose a different TNF-inhibitor altogether.” This is a weird finding, perhaps indicating nothing more than spite for the health plan’s benefit design. Clearly, if the physicians fully considered the evidence, they would be less likely to prescribe in this way. Admittedly, as notable numbers of managed care organizations have not actually mandated Inflectra use at this point in time, we would have to wait to see if this opinion is validated in actual practice.

Finally, Sanofi announced that it had received tentative approval on a follow-on biologic form of insulin lispro (the originator product was Lilly’s Humalog®). Patent issues will have to be resolved before Sanofi can receive final approval and bring this product to the market. The insulin biosimilars are not regulated under the Biologics Price Competition and Innovation Act, but rather under the Hatch–Waxman Act—the application was filed as a 505(b)2 rather than a 351(k) variety. They are transitional products, which will considered under the newer regulations after March 23, 2020. We will detail these lesser-known transitional drug categories in a future post.

Mylan and Biocon Withdraw Two EMA Biosimilar Applications

The biosimilar pegfilgrastim marketplace may have taken another hit today, as Biocon announced that it was pulling its applications for both pegfilgrastim and trastuzumab from consideration by the European Medicines Agency (EMA).

The action came after Biocon was notified of the need for re-inspection of its manufacturing site by the European authorities. According to Reuters, Biocon said in a stock filing, “The European regulatory authorities had informed us of the need for a re-inspection of our drug product facility for these products,” Biocon said, without specifying when the regulator would carry out the inspection.

Herceptin“We are on track to complete our corrective action and preventive actions by the end of this quarter, and it is our intent to seek re-inspection and re-submission thereafter.”

In another report, a Biocon spokesperson stated that “Whilst our drug substance facilities for trastuzumab and pegfilgrastim were approved, the European regulatory authorities had informed us of the need for a re-inspection of our drug product facility for these products. The request for withdrawal of the dossiers and re-submission is part of the EMA procedural requirements linked to this re-inspection and will be considered by the EMA’s Committee for Medicinal Products for Human Use (CHMP),” said the company spokesperson.

This action could potentially create considerable problems for the partners Mylan and Biocon. They have the opportunity to be first-to-market in the US with regard to both biosimilar products. Their biosimilar trastuzumab application received a unanimous recommendation to approve from the Food and Drug Administration (FDA) Oncology Drug Advisory Committtee in July, and a final decision is imminent (expected before September 3). The partners’ biosimilar pegfilgrastim application is expected by October 9th. Although the FDA usually rules according to its Advisory Committee recommendations, manufacturing plant problems has resulted in at least one surprising rejection, for Pfizer’s Retacrit®. Pegfilgrastim applications have not yet made it through the FDA approval process, after three previous attempts.   

Information is not readily available as to whether the Biocon plant that is subject to re-inspection would potentially be supplying products to the US. If so, the FDA may decide to review the situation, and possibly delay their decision or issue complete response letters on the two products.

Two New Trastuzumab Biosimilars Submitted for FDA Approval

The team of Mylan and Biocon may have some company in the biosimilar competition for Herceptin® (trastuzumab). Two additional partnerships announced the filing of their 351(k) applications for trastuzumab biosimilars.

Amgen and Allergan are hoping ABP 980 will have smooth sailing through the approval system. The phase 3 study in patients with early-stage HER2-positive breast cancer was completed in January 2017, with study results reported in July 2016. This study enrolled 725 patients, and yielded positive results in terms of safety, efficacy, and similarity to the originator product.

Celltrion submitted their product application for CT-P6 (Herzuma™) to the FDA on July 30 as well. Its partner Teva will distribute and market the product in the US, upon approval. The phase 3 study for this product is ongoing, but the results of the primary outcome data from 549 patients were published in June 2017. The outcomes were found to be similar to those of Herceptin.

Mylan and Biocon had submitted their biosimilar version on November 1, 2016. The FDA Advisory Committee reviewing their product gave it their unanimous support on July 13, and the final FDA decision is expected by September 3, 2017. If approved, Mylan will have at least a 9-month time advantage to get their foot in the door of a $2.6 billion trastuzumab marketplace.

This sets up a very interesting pricing dynamic. I had originally thought that this scenario might occur first with adalimumab after the patent litigation was resolved, but it is very possible that multiple biosimilars for trastuzumab may be launched first and in a very short timeframe.

Assuming Mylan gets the nod from FDA first, they have a couple of obvious paths they can travel: (1) launch with a substantial discount in an attempt to capture as much marketshare as possible before the other market entrants arrive or (2) launch with a modest (but attractive) discount in an effort to maximize their revenue while their product remains the sole biosimilar available. It will then be a guessing game as to how Amgen/Allergan and Celltrion/Teva play their turns in this poker game. With sudden market competition, such as their launches could potentially pose, payers may play a bit of a waiting game themselves, to see where the chips fall.