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.

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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®).

Sandoz Files 351(k) Application for Adalimumab Biosimilar

Sandoz announced that it has thrown its hat in the ring for another Humira biosimilar. Sandoz filed an European application for approval for GP2017 last year, in the expectation that it will be able to launch soon after the European patent expires in October 2018.

This will be the third application for an adalimumab biosimilar. Versions by Amgen (Amjevita) and Boehringer Ingelheim (Cyltezo) have been approved by the Food and Drug Administration (FDA); however, patent litigation has held up marketing. Amgen had signed an agreement with Humira’s manufacturer Abbvie to postpone marketing until 2023. Boehringer Ingelheim has not signed a similar agreement, but no indication is yet given regarding the US launch of this product.

It is assumed that European revenues will sustain the biosimilar manufacturers until US marketing begins. This is Sandoz’s fifth FDA biosimilar application. It has received approval for Zarxio (filgrastim) and Erelzi (etanercept); its application for rituximab is under review, and it received a rejection for its version of pegfilgrastim.

A Profile on Lesser-Known Player in the Biosimilar Space: Lupin Pharmaceuticals

On occasion, we profile some biosimilar manufacturers about whom our readers may not be as familiar as the large players like Sandoz, Amgen, and Pfizer. This generally refers to companies that have products that are in earlier-stage research or those who simply have not been in the news as often as their colleagues. In this post, we highlight a Baltimore-based company, Lupin Pharmaceuticals.

Lupin is a subsidiary of the Indian company Lupin Limited. It is perhaps best known as a manufacturer of generic drugs, especially anti-infectives.

Why you may be hearing more about this company: At a January JP Morgan investor conference, Lupin announced its intention to bring a biosimilar application for etanercept to the European Medicines Agency in early 2019, with a 351(k) application filed with the Food and Drug Administration the following year. Additionally, Lupin has indicated that it will be jumping into the biosimilar market with both feet, with early-stage development beginning for six other medications: aflibercept, denosumab, filgrastim, pertuzumab, pegfilgrastim, and ranibizumab. It believes that the combined global market for these agents is $24 billion.

Lupin has not announced any marketing partnerships, meaning that they may decide to go it alone, unlike some of the major players (e.g., Allergan–Amgen, Celltrion–Pfizer, Samsung Bioepis–Merck, etc). With its extensive generic portfolio, Lupin may believe that it has the sales force necessary to effectively market in the biosimilar space as well.

In other news…Novartis has announced an unusual clinical trial move. In its clinical trial program for secukinumab (Costentyx®), it has engaged in a head-to-head trial against both Humira® and its own (i.e., Sandoz’s) biosimilar version of adalimumab (GP2017).  The head-to-head trial with GP2017 focuses on the ankylosing spondylitis indication, whereas the Humira comparative-effectiveness trial involves patients with psoriatic arthritis.

Is There an Escape From the Rebate Trap?

The rebates given to pharmacy benefit managers to secure a drug’s place on the formulary have become a difficult barrier to coverage for new products. The rebate income for these PBMs is sometimes passed on to health plans, insurers, and employer purchasers, but more often it is not.

A big issue is that managed care organizations tend to become addicted to millions of dollars in rebate “income,” and this mindset prevents serious consideration of new medications at competitive costs. The health plans don’t see the benefit of incurring the administrative costs of moving masses of patients from the preferred product to a new one, or seeing this revenue stream interrupted, without an overall further improvement in net costs.

Managed care plans have long said that discounts of 25% or more will be necessary to release the rebate stranglehold of preferred products. In the case of infliximab, this has not yet occurred, based on recent minor inroads made by Merck’s Renflexis® biosimilar, despite larger discounts. Until greater competition is available, which drives down the WAC prices (and then average sales prices [ASPs]), barriers to accessing new medications will remain. In fact, when competition does increase, makers of the originator products, like Janssen, can simply ratchet up their rebates to maintain a hold on sales (and a billion-dollar plus profit).

Perhaps the best way around this is to force a change in the marketbasket. This can be accomplished in a couple of ways. The first, by instituting separate tiers for biosimilars and reference agents, takes the biosimilars out of the 1 of 2 preferred drug contracting restrictions, and allows patients to access biosimilars as well as preferred brands.

A second way is to reconsider biologic agents according to indication-based contracts or mechanism-of-action (MOA) based differences. Therefore, the marketbasket is modified to consider anti-TNFs separate from interleukins, allowing preferred agents in each separate category. This would allow, for instance, for more effective psoriasis agents to be well covered, and maintain the preferred position of Humira® and Enbrel® for appropriate patients.

A third way is to work out some innovative value-based contract, in which the manufacturer and health plan/insurer reaches an agreement on (usually) the expected outcomes of drug use and additional rebates or performance guarantees if the medication fails to deliver on this performance. The most important consideration in this agreement is the practicality of measuring an outcome of interest or ensuring adherence.

The rebate trap seems to be ensnaring more manufacturers of new biologics and biosimilars. Without greater consideration of the overall good, this trap can cause systematic problems for the pharmaceutical industry and discourage drug innovation and accessibility.

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%.

Exchange vs. Nonexchange Specialty Drug Use in Autoimmune Disorders

Some fascinating research has been published in the Journal of Managed Care and Specialty Pharmacy that has significant implications for the immunomodulatory marketplace, including biosimilars. In this article, researchers from HealthCore and Anthem found some real-world evidence that the costs and comprehensiveness of health insurance—and cost sharing—are linked to utilization and perhaps access to biologics to treat autoimmune diseases.

The specialty jmcp.2018.24.issue-1.coverdrug trend is increasing rapidly, and the autoimmune disorders (e.g., rheumatoid arthritis, psoriasis, inflammatory bowel disease, among others) are a significant slice of the specialty expenditure pie. It is assumed that access to, and utilization of, these agents may lower in those with higher deductibles and greater overall cost sharing. One excellent real-life laboratory to test this is in the health exchanges. Across the metal spectrum, premiums, deductibles, total cost sharing, and comprehensiveness of provider networks vary considerably. The researchers leveraged a large amount of data about Anthem subscribers in exchanges nationally and outside of exchanges. The resulting database for this study included 931,184 individuals across exchange plans and 2,682,855 insured through nonexchange Anthem plans.

Are Exchange Plan Members Really Sicker?

One of the expected hallmarks of exchange plan membership is that the population is sicker, requiring greater health expenditures (and greater risk) for the plan compared with people in nonexchange plans. The authors of this paper did not find much of a difference, however, between the groups. The exchange plans in general had an older membership (45.0 vs. 42.7 yr; P < .001) and greater female membership (52.7 vs. 49.0%; P < .001). However, their comorbidity scores and rates of the chronic inflammatory diseases investigated were very similar. Interestingly, their mean total health care expenditures were not significantly different ($2,792 vs. 2,783, respectively).

The most important finding was that despite these similarities, their use of biologic medications differed considerably. Broken down by plan category, the unadjusted utilization of specialty drugs to treat chronic inflammatory diseases (per 100,000 population) looked like this:

  • Nonexchange plans: 427 per 100,000 members
  • All exchange plans: 341 (20% below the nonexchange plan level)
  • Bronze plan: 132 (69% below the nonexchange plan level)
  • Silver plan: 326 (23% below the nonexchange plan level)
  • Gold plan: 579 (35.6% above the nonexchange plan level)
  • Platinum plan: 672 (57.5% above the nonexchange plan level)

Platinum vs. Bronze Plan: Morbidity Burden

When adjusted for demographics, previous use of nonspecialty drugs, comorbidities, and patient out-of-pocket drug costs, the variations decreased, but the step-wise progression remained (though gold plan members were found to be 1.4% less likely and platinum plan members were 12.6% more likely than nonexchange plan members to use a specialty drug for their autoimmune disease). They noted, “In our study, members enrolled in platinum plans had 2.4 times the comorbid conditions, 2.5 times the number of prescription fills, 3.3 times the prevalence of any chronic inflammatory diseases, and incurred 3.0 times higher total health care spending than members in bronze plans.”

One would expect higher deductibles and out-of-pocket costs have something to do with this trend. However, greater freedom in choosing providers and broader networks may well have an influence as well. It may also be that exchange plan members are more likely to try nonspecialty medications (e.g., methotrexate, prednisone, etc) before moving on to the biologics; yet, very few health plans fail to require other medications before these biologics are added to the mix.

The authors’ subanalysis of local markets found huge variations in specialty drug use, even though these were all Anthem plans with an assumed similar level of benefit (49% below to 75% above nonexchange plan specialty drug utilization in its local market). This demonstrates that despite the large populations analyzed, interpretation is highly complex and likely the result of many factors.

The study did not offer a breakdown of how many of these plans have a three-tier, four-tier, or five-tier benefit. Also, biologics that are covered on the medical rather than the pharmacy benefit are less likely subject to large out-of-pocket costs. On the other hand, these study results seem to suggest that less expensive biosimilars on a lower cost-sharing tier could improve access to biologics.

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?

A Pre-Holiday Gift for Pfizer—a Second Infliximab Biosimilar Approval. Now What?

On December 14, Pfizer got an early Christmas present, the approval by the Food and Drug Administration (FDA) of the second infliximab biosimilar in which it has a stake. First came Inflectra® in 2016, and here comes Ixifi™ (infliximab-qbtx). Unlike Inflectra, which Pfizer markets for Celltrion, Ixifi is Pfizer’s alone—Web image for headera product that was under development at the time of the acquisition.

This of course puts Pfizer in an interesting position. Ixifi would be the third infliximab biosimilar to reach the market, after Inflectra and Samsung/Merck’s Renflexis™. True, Inflectra has limited marketshare in the US, and competition from more heavily discounted Renflexis could compound the situation.

It seems that Ixifi is not intended to reach the US market at all, and may be marketed in other countries where the Celltrion agreement does not hold sway. However, this begs the question: Why did Pfizer decide to go apply for a 351(k) application for FDA approval? That is unclear at this time. Perhaps they will use this biosimilar as insurance if Inflectra does not perform as promised. On the other hand, Pfizer could license it to another manufacturer and collect additional royalties from its sales in the US and overseas.

For those of you who guessed the last choice, congratulations! Under a deal signed in early 2016, Sandoz obtained the rights to market this agent in the European Economic Area. This would enable Pfizer to earn cash rewards and other prizes from two biologics in the same biosimilar category.

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.

A Health System Biosimilar Survey’s Implications

When asked about potential cost savings with the infliximab biosimilar, nearly one-quarter of health system respondents did not believe that it represented a cost savings opportunity for their organization, according to a newly published survey in the Journal of Managed Care and Specialty Pharmacy.

Conducted by Premier, Inc., a group purchasing organization, 57 US health systems responded to its questionnaire in April and May 2017 (before the launch of Merck/Samsung Bioepis’ Renflexis® biosimilar). All of the health systems currently used infliximab at their facilities.

The greatest barrier to adoption cited by the health systems was the reimbursement from payers (28%), with actual cost of the biosimilar being a lesser concern (10%). According to the survey, about one-third of the respondents had had communications by that time with payers regarding the latter’s approach to biosimilar coverage.

Interestingly, 62% of those systems represented by the survey respondents had not reviewed Pfizer’s Inflectra® in their Pharmacy and Therapeutics Committees. In large part, thiBR&amp;R Logo Transparent1.5-21-2017s was a continuation of a “wait-and-see” approach, particularly in view of the relatively small discounts offered by Pfizer. Others responded that they were awaiting Merck’s entry into the marketplace, to review both biosimilars at the same time.

“For sites of care that approved formulary addition of the infliximab biosimilar, implementation strategies ranged from full product conversion to ‘new patients’ only,” wrote the author, Sonia T. Oskouei, PharmD, Director of Pharmacy Program Development-Biosimilars at Premier. “Some sites added it to their formularies as a preferred product but only when payer coverage supported it.”

Seventy-six percent of respondents perceived that there was a cost savings opportunity for biosimilars compared with the reference product. What are the expectations of the remaining health system executives? If they don’t believe biosimilars do not save the system money, why not?