Tag: biosimilars

Teva’s Syprine Generic Priced 14% Below Jacked Up Valeant Product Price

In an announcement that surprised few, Teva Pharmaceuticals announced that its generic version of trientine hydrochloride (Syprine®) for the treatment of Wilson’s disease will be sold for a very nongeneric price. Also unsurprising, Teva executives did not address the fact that the price of Syprine had been jacked up astronomically by Valeant Pharmaceuticals only recently, to $21,267 in 2015 froTeva Pharmaceuticals, maker of the new generic for Syprinem a mere $652 in 2010. Also, Syprine had been available since 1969.

An outrage? Yes of course, but not surprising for a number of reasons. Wilson’s disease is an extremely rare disease, on the order of 5,000 patients. At a price of $652 per person, the resulting revenue might be a paltry $3.2 million.

In preparation for launch, Teva evidently looked at its options for discounts based on the current list price, not the pricing from several years ago. This is also unsurprising. However, the discount offered is not great—$18,375 for a bottle of 100 pills.

Wilson’s disease is the result of a genetic disorder of the liver that causes hepatic cells to accumulate and store excess copper. The disease impairs the liver’s ability to excrete copper into the bile and then into the gastrointestinal tract. The copper build-up is toxic to the liver, and can cause cirrhosis and death. Ordinarily treated with d-pencillamine, patients can be intolerant to it and require additional therapy, such as trientine.

As most payers know, generic pricing today is unlike generic pricing of the past. Even relatively simple compounds, available for decades, are subject to competitive forces like number of mBiosimilars news, reviews, and reportsanufacturers and supply. However, demand seems to be the one market force that is not in play. With so few potential patients, overall demand would seem low, particularly with pencillamine already available to treat patients.

Teva’s pricing could have reflected the reality of 2010 or the reality of 2018. The company chose the latter, which so many others would also do today. If an additional generic was introduced into the market dynamic (though unlikely due to the demand), pricing (or at least net costs) could be strongly affected.

Payers hope to see this dynamic play out in the biosimilars arena as well. With a single biosimilar agent competing against the reference product, the retail cost discounts have been small. But with the introduction of additional competition, net costs (if not wholesale average costs) will fall rapidly.

Pfizer US Biosimilar Revenues Growing Slowly, Better News Internationally

According to an article posted on the Market Realist website, Pfizer’s US and global biosimilars revenues are growing, but its sales of Inflectra® remainPfizer Headquarters stunted.

In the fourth-quarter of 2017, the New York–based company posted US biosimilar revenues of $44 million—all attributable to its infliximab biosimilar. The product was launched in Q4 2016 (and gained only $4 million in revenues), but the revenue was reported to be somewhat higher than in Q3 2017. Total 2017 Inflectra revenue was $118 million.

Internationally, where Pfizer not only markets Inflectra, but its Retacrit® form of epoetin alpha and its Nivestim® brand of filgrastim, biosimilars contributed $531 million to the bottom line in 2017, an increase of 37% compared to the previous year.

There is little doubt that Pfizer’s US Inflectra revenues will continue to increase, but competition from Samsung/Merck’s Renflexis® and Janssen Biotech’s continuing heavy rebates on Remicade® should prove challenging to Pfizer. Merck has not yet reported its Q3 or Q4 sales of Renflexis, which was only launched in July 2017.

Pfizer’s second US biosimilar approval was also for an infliximab biosimilar (a legacy product from its Hospira acquisition). This agent, infliximab-qbtx, dubbed Ixifi™, was approved in December 2017 and will apparently not be launched in the US.

 

Its next big splash into the US biosimilars market may not occur in 2018. Its rituximab biosimilar (PF-05280586) met its primary outcomes measures in a phase 3 trial, as announced in January, but no target date has been yet reported for its 351(k) application to the Food and Drug Administration (FDA). However, this product may face stiff competition from Celltrion and Sandoz for their rituximab biosimilars currently being reviewed by the FDA. Celltrion is partnered with Mylan (not Pfizer) in the commercialization of its rituximab biosimilar.

A Profile on Lesser-Known Player in the Biosimilar Space: Alteogen Inc

On occasion, we profile some biosimilar manufacturers about whom our readers may not be familiar. 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 South Korean-based company, Alteogen Inc.

Established in 2008, Alteogen is focused on the development of bio-betters, with an emphasis on increased half-lives. It is a fairly new player in the biosiAlteogenmilar field, however, and has  partnered with Chinese, Japanese, and Brazilian companies to advance the development of at least two biosimilars.

 

 

 

Why you may be hearing more about this company: Its lead product, a biosimilar of aflibercept (originator product Eylea®) for the treatment of macular degeneration, has just completed preclinical testing. They have announced their intention to file this year with the US Food and Drug Administration to begin the clinical trial process of ALT-L9. Additionally, Alteogen is beginning the drug characterization process for a version of trastuzumab.

Whereas both agents are several years away from potential marketing, Alteogen believes that ALT-L9 may demonstrate some distinct advantages over Regeneron’s originator product. The manufacturer believes that potential benefits include better storage and transport characteristics, including longer dates to expiration and resistance to high temperatures. The company points to proprietary technology which may help it to achieve this “bio-better” status in the biosimilar space with trastuzumab. Its website says that using “an antibody drug conjugate technology conjugating the anti-cancer chemical drugs to an antibody protein… is a technology for the next generation anti-cancer therapeutics, which increase the effectiveness and reduces side effects of the anti-cancer cells directly.” It has applied this technology to trastuzumab, and this agent (ALT-02) has completed a phase 1 trial.

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®).

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.

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?

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?