Tag: Pfizer

Coauthor of Hatch–Waxman Act Attacks the Use of IPR Process for Biosimilars

The Hatch–Waxman Act (officially, The Drug Price Competition and Patent Term Restoration Act of 1984) enabled generic medications to be marketed after branded patent expirations. One of the bill’s cosponsor, Senator Orrin Hatch (R-UT), is now spurring a legislative proposal that would protect reference drug manufacturers from use of the inter partes review (IPR) system. This action would result in further delayed access to lower-cost generics and biologic medicines.

Inter partes review is used by makers of generic drugs and biosimilars to challenge weaker patents. It enables the parties to bypass lengthier litigation through the courts, potentially helping less-expensive drugs reach the market faster than otherwise possible.

Hatch-Waxman Act
Senator Orrin Hatch (R-UT)

Called the Hatch–Waxman Integrity Act, this amendment to the CREATES Act was introduced December 11, 2018 simultaneously into the Senate and the House (by Representative Bill Flores, R-TX). If passed this amendment could significantly limit the ability of generic and biosimilar manufacturers to use the IPR process to speed patent review and litigation.

Seemingly a contradictory stance by Senator Hatch, he believes that the IPR process may too strongly affect the balance between access to medications and biopharmaceutical innovation.

In any case, this proposal would have a very difficult road to passage. First the administration’s current efforts to make biosimilars available as soon as possible runs counter to this bill. Second, the shift to the Democratic majority in the House could be an insurmountable barrier to passage.

In other biosimilars news…Sandoz seems to be entering the biosimilar insulin marketplace, with its agreement to commercialize three different types (insulin aspart, glargine, and lispro) that will be manufactured by the Chinese company Gan & Lee. Sandoz will be responsible for the US and Canada, the EU and Switzerland, Australia and New Zealand, and Japan. In the US, insulin makers can file applications for biosimilar status as of 2020.

Additionally, Pfizer received good news from Europe, receiving a positive recommendation from the EMA’s Committee for Medicinal Products for Human Use (CHMP) on its bevacizumab biosimilar Zirabev (reference product, Avastin®).

Pfizer Pulls One Biosimilar Adalimumab Application From the EMA

Earlier this month, Pfizer notified the European Medicines Agency (EMA) that it was withdrawing one of its two applications for approval of its biosimilar adalimumab. 

According to Pfizer’s Director of Global Media Relations, Thomas Biegi, the company had submitted two applications for this biosimilar, one for a limited set of indications, and the other for the full array of autoimmune indications of the reference product Humira®. Pfizer has decided to focus on gaining approval for the full slate of indications and withdrew the other application. Under the “skinny label,” the product would have been marketed as Fyzoclad™ in Europe. The potential brand name of the biosimilar if  approved with all of the reference product’s indications was not disclosed. In the US, the biosimilar is still known as PF-06410293 .

Although Pfizer would not confirm its plans for the US filing, phase 3 trial results for PF-06410293 have been published, establishing the biosimilar’s equivalency to Humira in terms of efficacy, safety, and immunogenicity.

PrintPfizer noted in its December 5th letter to EMA that their decision was not related to safety or efficacy. No doubt, Pfizer is surveying the heavy competition for adalimumab in Europe today. Pfizer did not elaborate on why the decision was made to submit applications for both the skinny label and the full set of indications.  

Pfizer signed a licensing deal with Abbvie on November 30 to market this adalimumab biosimilar in the US. It will be the sixth biosimilar to enter the market in 2023, based on this deal. Therefore, Pfizer must believe that a sixth biosimilar entrant to the US market at that time may still yield relevant revenues and marketshare. 

According to EvaluatePharma, Humira US sales estimates (published in 2018) for 2020 will be about $21 billion. By 2024, this company believes Abbvie’s share of the revenue will be a bit more than $12 billion (which is not much different than today’s figures). If this guess is accurate, that leaves $9 billion for seven or so biosimilar makers. If the guess is very inaccurate, and Abbvie is left with far less revenue because of the competition and falling prices, then any number of adalimumab biosimilar manufacturers could attain more than $1 billion in sales. 

In other biosimilar news…Amgen has announced the filing of a new biosimilar version of infliximab. ABP 710 was the subject of a phase 3 trial in patients with moderate-to-severe rheumatoid arthritis; researchers concluded that the drug was equivalent to Remicade® in terms of efficacy, safety and immunogenicity. Today’s filing would put this biosimilar on a path to a late Q3 or early Q4 2019 decision by the FDA. If approved, ABP 710 would be the fourth infliximab biosimilar approved in the United States (Pfizer’s Inflixi® is also approved but will only be sold overseas).

 

This post was updated and corrected on December 18, 2018.

Pfizer Signs Licensing Agreement With Roche on Trastuzumab Biosimilar

With Pfizer expecting to hear back on its 351(k) resubmission on a trastuzumab biosimilar in early 2019, Genentech and its parent, Roche, may have been getting nervous about their competitor’s intentions. After all, Pfizer was willing to launch at risk with its marketing of Inflectra®, the infliximab biosimilar manufactured by partner Celltrion. In fact, it is the only biosimilar manufacturer that has gambled on an at-risk biosimilar launch.

According to a report in the Pink Sheet, a district court filing on December 4 noted that the two parties signed a settlement that will put an end to their patent litigation, and presumably allow Pfizer to market its biosimilar trastuzumab in the US at a future date. As in previous agreements signed by Roche, the terms are confidential, and launch dates and licensing fees are unknown.

trastuzumab biosimilar

A similar confidential agreement was completed between Mylan and Roche, for Mylan and partner Biocon’s Ogivri®, the first trastuzumab biosimilar approved by the Food and Drug Administration (FDA) in April 2017.

Three other trastuzumab biosimilars are also trying to reach the market. Amgen and Allergan received a complete response letter in June 2018, and have not yet announced when it might resubmit its 351(k) application. Samsung Bioepis is awaiting its initial decision on its trastuzumab biosimilar, filed in January 2018. Teva and Celltrion seem to be on the cusp of an FDA decision, after receiving their initial rejection in July 2017.

Roche has it covered, though. It filed patient litigation against Samsung Bioepis in September 2018 and partners Celltrion and Teva as well.

This is the very situation that the federal government, payers, and patients want to try to avoid, however. Licensing fees paid to the reference manufacturers may work to significantly inflate the drug’s price to the health system. The lack of transparency characterizing these agreements and the associated delays in launch are being decried by those patients and entities who can benefit from access to biosimilar competition. Herceptin was first approved in 1998. No one envisioned Genentech having 20+ years of marketing exclusivity.

In other biosimilarnews… MomentaPharmaceuticals, which signed an Abbvie licensing agreement for its biosimilar adalimumab, said in a statement that it will delay FDA filing M923 beyond 2019, which will help reduce its corporate expenditures. This delay should not impact the expected commercial launch date of November 20, 2023, according to the company.

Celltrion announced that it has filed an application for European Medicines Agency approval for its subcutaneous form of its infliximab biosimilar Remsima (US brand name, Inflectra®). This would provide the first subcutaneous injection formulation of infliximab.

Pfizer Launches Retacrit, First Biosimilar Version of Epogen and Procrit

On November 13, Pfizer began marketing its biosimilar version of epoetin alfa. Pfizer launches Retacrit® at a 33.5% discount to Amgen’s reference product Epogen®.

Retacrit was originally developed by Hospira, which Pfizer acquired in 2015. Retacrit was one of the first biosimilars approved in the EU. It had a long journey to reaching the market in the US, however, including rejections by the FDA for manufacturing plant problems. It was finally approved by the FDA on May 15, 2018. The Retacrit launch comes 180 days after the approval.

The wholesale acquisition cost (WAC) of this biosimilar will be $11.03 per 1,000 units/mL, which represents an even steeper discount (57%) to Epogen’s sister product, Procrit® by Johnson & Johnson.

For Pfizer, this represents their third biosimilar being marketed today (along with Inflectra® and Nevistym®).

Pfizer’s Anticompetitive Suit: A Slippery Slope to Competitive Bidding?

When Pfizer first announced its lawsuit against Janssen’s parent Johnson & Johnson in September 2017, it pointed to exclusionary contracting, “anticompetitive” behavior of Remicade®’s maker as the reason for its very limited market access.

The lawsuit claimed that Janssen has withheld or threatened to withhold rebates if payers do not keep Remicade in an exclusive preferred position. The degree to which health plans knuckled under to these demands may only be inferred from the 3% marketshare Pfizer’s Inflectra® now holds. For these drugs, which are still typically covered under the medical benefit, “nonpreferred positioning” usually means no coverage. For drugs covered under the pharmacy benefit, this is not the case.

In August, the Eastern Court of Pennsylvania ruled against J&J in its request that the lawsuit be dismissed. While discovery in the case may be ongoing, we could not find mention of a resolution date for the suit.exclusionary contracting

For the sake of argument, let’s say that the Eastern Court of Pennsylvania rules in favor of Janssen. In other words, exclusionary contracting was not an anticompetitive behavior. That means the status quo is intact, but some factors may affect this situation going forward. These include the Center for Medicare and Medicaid Services’ desire to move part B drugs (the medical benefit) to part D (the pharmacy benefit) for Medicare beneficiaries.

The scrutiny on rebate contracting coming from several sectors, and lack of transparency, may also independently influence future use of these pharmaceutical company tactics. I helped conduct a market research project recently on a nonspecialty drug. As part of these interviews, we were asked by the client to inquire about the range of rebates they were receiving from competitor manufacturers. Their responses were requested as a range (e.g., 20% to 30%), not specific contract details, and we had no intention of providing reports of individual payer deals, only anonymous, aggregate information. We expected little to no response to that query, and that is exclusionary contractingexactly what we received.

Let’s discuss the other potential outcome, in which the Court rules in favor of Pfizer. That implies that this exclusionary contracting practice is indeed anticompetitive. If this is the case, we may be on a very slippery slope. What is the difference between payers and pharma companies engaging in a “1 of 1” contract when there are multiple potential products and a “1 of 2” contract? In both cases, drug makers are committing payers to anticompetitive behavior (as perhaps defined by the Court’s new precedent).

The preferred drug tier (whether preferred generics, preferred brands or whatever) is supposed to be for products with proven clinical, patient care, or economic advantages. Truthfully, payers rarely place medications in the preferred tier for reasons other than net costs or rebate contracting, which is based on marketshare.

Now add in the potential effects of the Administration’s desired shift to part D, where pharmacy benefit rules can be applied. That exposes injectable products that were shielded under Medicare part B to commonly applied formulary placement practices.

To be complete, Janssen’s strategy was not solely based on Remicade. It may be found to have bundled Remicade with other agents in deals to exclude Pfizer’s products. The Court may also react specifically to Janssen’s contract stipulation that threatens to withhold rebates connected to future use of the product, to increase its leverage.

However, if the Court determines that 1 of 1 or exclusionary contracting with rebates are the root of the anticompetitive behavior, why should 1 of 2 or even 1 of 3 contracts in a drug category with 5 similar agents be less so? This is the slippery slope that could undo rebate contracting, and push us towards a system that more resembles a competitive bidding process like in Europe. Alternatively, it could accelerate the move towards outcomes- and value-based contracting. The result could be a system-wide revamping of the drug formulary and the pharmacy–drug maker relationship.

In other biosimilar news…Sandoz has signed a licensing agreement with Abbvie, allowing it to market its biosimilar version of Humira in 2023. The agreement, as with Abbvie’s settlements with other biosimilar makers, halts all patent litigation with Sandoz in exchange for a licensing royalty paid to Abbvie.

Biosimilars and Drug Rebates: A Foot in the Door to Access?

At the September 5–7, 2018 GRx+Biosims meeting, I had the opportunity to moderate a session with three highly experienced biosimilar industry executives. They included Gary Deeb, Senior Vice President, Global Licensing and Business Development, Lupin Pharmaceuticals; Chrys Kokino, MBA, Head Global Biologics— Commercial, Mylan; and Mike Woolcock, MBA, Senior Vice President, Commercial Operations, Apobiologix. In the hour-long session, we covered a range of sticky topics. This post sums up some of the information gained on one aspect—the question of price transparency, recent FDA action to address drug rebates, and whether deemphasizing drug rebates will help biosimilars gain access.

One issue that is getting an awful lot of attention lately is the question of price transparency. This has been highlighted by the difficulties that Pfizer has had in gaining traction for its infliximab biosimilar, resulting in claims of exclusionary contracting by Janssen to protect the latter’s marketshare. One of the principal tools used by the reference biologic manufacturer is its power to rebate. When a drug has the lion’s share of utilization, rebates become very potent inducements to payers to provide or maintain preferred or exclusionary status on formulary. Therefore, the issue of biosimilars and reference drug rebates can be an important one for the industry.

biosimilars and rebatesIn response to the challenges of biosimilars gaining uptake in the US, Health and Human Services Secretary Alex Azar has been investigating whether safe harbor laws that currently protect drug rebates from anticompetitive lawsuits can be changed. This move can affect revenues for both pharmacy benefit managers (PBMs) and payers who share in the rebate monies. It raises a related question, however: Would biosimilar manufacturers be better off competing on list pricing (i.e., wholesale acquisition cost) alone? And does the issue of biosimlars and rebates really matter?

In the backstage green room, this topic generated much discussion among our panelists. And quite frankly, the answer to this question is not yet in.

In previous market research and access projects performed for pharma and their agencies, it has been clear that health plan medical directors and pharmacy directors would prefer competition based on discounted WAC, whereas PBMs prefer to retain their rebate revenue. However, the plans do share in drug rebate revenue to varying extents, which they are quick to point out are helpful in holding down premium increases or funding other projects beneficial to members and patient care. Hence, they are stuck in the rebate trap as well. They are not generally eager to add a new preferred drug even if the manufacturer is offering powerful discount WAC plus competitive rebate; they realize that the rebate revenue is based mostly on how much marketshare the drug maker can gain (and how quickly it can amass marketshare).

The biosimilar industry representatives at our panel discussion were similarly reticent. Does it represent an opportunity to break the exclusionary contracting hold of companies like Janssen? Without high rebates to cement a reference drug’s place as a preferred or the only covered biologic, other manufacturers can get their foot in the door and compete for marketshare based on price alone. This does not mean that prices would necessarily be more transparent, however. One would expect that discounted prices negotiated (from one plan to another or one PBM to another) would differ and remain confidential in nature. In other words, Kaiser Permanente Southern California could still only guess what Blue Shield of California was paying for infliximab and vice versa.

If the average sales price (ASP) methodology were unchanged, one would expect the ASP, which reflects discounts and rebates, to be closer to the WAC price by the amount no longer rebated. But the wild card in this scenario would be the pharmaceutical and PBM industries’ reaction. Is there a way to reclassify rebates as some other payment, like “administrative fees”? Our panelists believe that the PBMs, for example, will not easily forfeit a revenue line representing pure profit, regardless of its size. One would need to anticipate some attempt to retain this revenue.

The issue of biosimilars and drug rebates may only be shifted, in the end. Payers would still want to see the lowest net cost for any product. In 2018, they don’t care too greatly about how this is achieved, through rebates, discounts, portfolio contracts, or other means. If pharmaceutical rebates were deemphasized, my own guess is that at least biosimilar manufacturers would not be disadvantaged once approved, simply because they don’t have any existing marketshare. And it would also test a payer’s fortitude in foregoing its own drug rebate revenue.

Pfizer Gets FDA’s Green Light on Its Filgrastim Biosimilar

Pfizer's Biosimilar Filgrastim
FILE PHOTO – The Pfizer logo is seen at their world headquarters in Manhattan, New York, U.S., August 1, 2016. REUTERS/Andrew Kelly/File Photo

On July 20, the US Food and Drug Administration (FDA) approved the second biosimilar version of filgrastim. Pfizer’s filgrastim biosimilar is named Nivestym™ (filgrastim-aafi).

The originator product, Amgen’s Neupogen®, has steep competition from two other products (Sandoz’s Zarxio® [filgrastim-sndz] and Teva’s Granix® (tbo-filgrastim]). Granix was approved as a follow-on biologic, before the biosimilar pathway was implemented.

The FDA granted Nivestym the following indications:

  • To decrease the incidence of infection, as manifested by febrile neutropenia, in patients with nonmyeloid malignancies receiving myelosuppressive anti-cancer drugs associated with a significant incidence of severe neutropenia with fever.
  • For reducing the time to neutrophil recovery and the duration of fever, following induction or consolidation chemotherapy treatment of patients with acute myeloid leukemia (AML).
  • To reduce the duration of neutropenia and neutropenia-related clinical sequelae, e.g., febrile neutropenia, in patients with nonmyeloid malignancies undergoing myeloablative chemotherapy followed by bone marrow transplantation (BMT).
  • For the mobilization of autologous hematopoietic progenitor cells into the peripheral blood for collection by leukapheresis.
  • For chronic administration to reduce the incidence and duration of sequelae of severe neutropenia (e.g., fever, infections, oropharyngeal ulcers) in symptomatic patients with congenital neutropenia, cyclic neutropenia, or idiopathic neutropenia.

Although a launch date was not announced for Pfizer’s filgrastim biosimilar, the company’s press release stated that “Nivestym is expected to be available in the US at a significant discount to the current wholesale acquisition cost (WAC) of Neupogen.”

Rather than competing aggressively for the filgrastim market, Amgen seems to be focusing its efforts on its pegfilgrastim brand, a longer-lasting version. Specifically, it is seeking to move its utilization to the Onpro formulation of Neulasta®. The first biosimilar to pegfilgrastim was approved in June (Mylan and Biocon’s Fulphila™).

Infliximab Biosimilars Savings Could Exceed $400 Million Dollars Annually

Everyone with an opinion believes that biosimilar drug use will save the health system considerable money. Calculations for biosimilar savings have been hampered by several factors. For example, previous high estimates have not been based on real-life scenarios. Only 3 biosimilars have been launched and utilized in the US; so little experience has been gained on which to base calculations.

Yet, isolating the savings associated with a single approved biosimilar does put their potential into perspective. It also demonstrates the promise of cumulative biosimilar savings with their launch and uptake. Based on current infliximab average sales prices (ASPs), wBiosimilar Savingshich considers discounts and rebates, one organization believes that a 50% marketshare for biosimilar infliximab could result in well over $400 million in annual savings system wide.

The analysis, conducted by Wayne H. Winegarden, PhD, Senior Fellow in Business and Economics, Pacific Research Institute, accrued the lion’s share of the annual savings to employer-sponsored health plans ($262 million to $315 million, compared with no sales of infliximab biosimilars). Medicare accounted for up to $150 million savings annually.

Dr. Winegarden tested several scenarios. The calculation considered the cost of the infliximab regimen based its various indications. He calculated biosimilar savings using different add-on percentages to ASP (including the current ASP + 4.3% payment and up to ASP + 20%), as well as different marketshares of the biosimilars (from 10% to 90%).

The current marketshare of the two available infliximab biosimilars—Inflectra® and Renflexis®—is below 5%, based on data from the first quarter of this year. This is partly because of Janssen’s tactics in matching the net costs of biosimilars with additional rebates on Remicade. This raises two important points: Dr. Winegarden’s analysis reveals savings accruing to the health care system (not necessarily to the payer). Also, the very existence of infliximab biosimilars has resulted in significant net savings compared with the price increases seen prior to their introduction.

It is a bit more difficult to pinpoint the system savings resulting from the use of the first biosimilar approved in the US, filgrastim-sndz (Zarxio®). The other branded product, tbo-filgrastim (Granix®), was launched a couple of years earlier and gained its own marketshare from the reference brand Neupogen®. No doubt, Zarxio contributed to some level of cost savings. In other words, the infliximab example is an easier calculation with a cleaner result.

With eight biosimilars for six reference products awaiting their turn to hit the market, and drugs like adalimumab and etanercept among them, it is easy to see how biosimilars savings can easily exceed $10 billion. Just not yet.

FDA Advisory Committees on Biosimilar Applications: Mylan’s Latest Muddies the Waters Further

When the Food and Drug Administration (FDA) approved the first biosimilar pegfilgrastim (Mylan’s Fulphila™), it broke precedent in more ways than one. Not only was this the first biosimilar member of the pegfilgrastim class to be approved, but its approval did not require an FDA Advisory Committee recommendation.

The FDA has been a bit fuzzy with respect to when an FDA Advisory Committee will be necessary. In the past, however, these AdComms had been required for all first biosimilar approvals to a new reference product. This was the case for filgrastim, infliximab, etanercept, trastuzumab, bevacizumab, adalimumab, and epoetin. Second biosimilars did not always require an AdComm, most recently last September with Boehringer Ingelheim’s Cyltezo®, the second adalimumab approved by FDA.

FDA Advisory CommitteeVarious problems with the 4 pegfilgrastim biologic license applications and resubmissions have provided the FDA ample time to review data and mull the consequences of approval or rejection. This case could be an exception. A greater challenge may be upcoming though.

Not that a great deal was achieved with the biosimilar AdComms. In general, votes for recommended approvals have been unanimous or lopsided. A recommendation for approval does not always result in approval—sticky manufacturing issues have gotten in the way (e.g., for Pfizer’s Retacrit). The FDA Advisory Committee meetings does give the public and other stakeholders a chance to air their views. Generally, this has been not for or against the biosimilar being reviewed but for or against biosimilars as a whole.

In March, I raised the case of Adello Biologics, which is attempting to gain approval of its filgrastim biosimilar without any phase 2 or phase 3 clinical data. This may be the second filgrastim biosimilar approved, so the FDA can avoid an AdComm on this basis. More importantly though, this agent could be the first biosimilar approved without any patient-based clinical testing (phase 1 is usually conducted in healthy volunteers). The next FDA Blood Products AdComm is not scheduled until November 29, 2018, and we do not know if Adello’s product will be part of that discussion. With a submission date of September 2017, one would expect a decision from FDA in the third quarter of this year.

In other biosimilar news… Celltrion resubmitted its 351(k) application to the FDA for its biosimilar version of trastuzumab. The original application resulted in an April 5 complete response letter for the Celltrion/Teva team.

Convincing Two Main Providers the Key to Pfizer’s Retacrit® Success

An unusual market situation awaits Pfizer’s new biosimilar epoetin, one that few approved medications has to face. Not only does Retacrit® need to pass muster with payers like health plans and insurers, which we assume it will, but Retacrit will need to be accepted by the two 800-pound gorillas of the kidney dialysis field as well.

epoetin use in kidney centersRetacrit and Dialysis Centers

The different part of this discussion is that providers are not usually so concentrated except in the treatment of the rarest diseases. Cancer medications are utilized by independent treatment centers throughout the country. Biosimilar agents like infliximab are also used throughout the nation by hospitals, large medical groups, and solo practices. In the case of epoetin, its primary use is in anemia related to kidney dialysis. The vast majority (85%) of kidney dialysis centers are owned by one of two networks, Fresenius Medical Care North America and DaVita Kidney Care. According to a report by Healio, Fresenius accounted for 42.6% of the total patient market in 2017, and DaVita is just behind, with 42.0% of the 453,000 patients receiving dialysis services. In other words, get buy-in from these companies and the payers, and Pfizer would have a chance to gain significant share of the epoetin market.

kidney dialysis centers
Source: https://www.healio.com/nephrology/practice-management/news/online/%7Bd894132b-b577-435e-8dec-401cd89d1b1e%7D/the-largest-dialysis-providers-in-2017-more-jump-on-integrated-care-bandwagon

Nephrologists seem to be onboard, in general. The results of national survey of nephrologists conducted in March 2018 confirm this. According to the research, only one in five respondents would be averse to switching to the biosimilar. One barrier to use may exist, however, on the provider side. The long-acting agents may be preferred by some. These include Amgen’s darbepoetin alfa (Aranesp®) and Roche’s Mircera® (methoxy polyethylene glycol-epoetin beta). To the extent that nephrologists may be less willing to use short-acting biosimilar instead of the more expensive long-acting brand may define Pfizer’s success with Retacrit. This is somewhat similar to the situation brewing with the use of injectable biosimilar pegfilgrastim (once approved and available) and the Neulasta® Onpro® delivery system. The share of use of the long-acting erythrocyte-stimulating agents has been increasing.

On May 15, 2018, Pfizer’s epoetin biosimilar Retacrit was approved by the Food and Drug Administration (FDA), the first biosimilar competitor to Epogen® and Procrit®. Retacrit is not officially available yet.

In other related biosimilar news…Pfizer announced that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has recommended marketing approval for its biosimilar version of trastuzumab.

Apotex and its Apobiologix division has claimed a significant prize—the first pegfilgrastim biosimilar approval in Western markets. None have been approved in the US or EU to date. Health Canada granted marketing authorization to the company on June 1. The new drug will be called Lapelga™.