Monday, March 09, 2020

FDA/FTC Workshop on a Competitive Marketplace for Biosimilars

FDA Licensure Process and U.S. Biosimilar Markets   [I entered in media res]

· Eva Temkin, Acting Director for Policy, Office of Therapeutic Biologics and Biosimilars,  CDER, FDA  
· Christine Simmon, Executive Director, Biosimilars Council, AAM: barriers to entry for biosimilars: exclusionary contracts, rebates, stakeholder misinformation. misinformation can include explicit and implicit, including policies such as naming conventions and the very existence of the interchangeable category, which is unique to the US.  [I think she was saying that the existence of the interchangeable category may mislead consumers about the suitability of the existing approved biosimilars; right now all approved biosimilars are approved for substitution but not for interchangeability, the latter of which means that there’s evidence that patients can go back and forth between the drugs as opposed to switching once.]  
· Molly Burich, Director of Public Policy, Boehringer Ingelheim   
· Surya Singh, President, Singh Healthcare Advisors, LLC  
Moderated Panel Discussion  
Meredyth Andrus, Attorney, Health Care Division, Bureau of Competition, FTC

Does the designation of interchangeability still have value in the US?
[I don’t think I can attribute statements given where I am in the room and what I can see.] Depends on the product. Primary draw: automatic substitution that can occur at pharmacy level. If the drug isn’t distributed that way, then there isn’t much point. All 15 approved/in use products are physician administered. There are several approved self-administered biosimilars, but none actually launched; have some time before we see products where interchangeability would make a difference.

Have heard from pharmacists that a different name may deter them from switching/may deter patients. Some state laws on this may also have to be addressed.

Why are 11 of 26 biosimilars approved not actively marketed in the US?

Singh: (1) patent thickets. One drug has over 100 patents, 89 of which filed after the drug was launched. (2) commercial & contracting issues. Same manufacturers/partners are innovator/originator of biologic and also of biosimilar. (3) Rebates. Different on medical benefit (physician-administered) side from pharmacy benefit side. If a few major entities are doing most of the contracting on the pharmacy benefit side, bundling is more common compared to more splintered market for doctor-administered drugs. Manufacturers are waiting to see if the rebate trap is going to be addressed.

Susan Collins introduced bill to require patents to be listed in Purple Book for biosimilars. Would help litigation, clarity. $3 million to litigate a patent, which is a big expense. Humira: 5 biosimilars approved, none on the market; some will be entering, but only b/c of patent settlement agreements. 11 years earlier than otherwise might be possible. FTC has done a lot to ensure that patent settlement agreements are pro-competitive; put the rest the idea of pay for delay. Inter partes review is good but is under threat.

Singh: [discussion of market structure/treatment modalities] doesn’t think that misinformation influences providers’ decisions. Survey data, leaders at large practices: there’s no more reluctance to use biosimilars. The market is being driven by economics. [One way to read this is as a terrific indictment of our broken health care system.]  Explanation of how contracts can limit doctors from using the drug of choice for patients: specialty pharmacy delivers drug to practice despite what they have chosen for inventory. “Fail first” policies are used extensively and increasingly for medical benefit (doctor delivered) drugs to ensure use of their preferred drugs. When a practice chooses what biosimilar to prescribe, it’s in inventory and interchangeability doesn’t matter. Pharmacy benefit side: now interchangeability does matter—the pharmacy needs the right to substitute w/o going back to prescriber, and the only way to get that right is interchangeability.

FDA and FTC Approaches to Help Ensure Truthful and Non‐misleading Advertising and
Promotional Communications

Lowell Schiller, Principal Associate Commissioner for Policy, FDA: have seen troubling communications suggesting biosimilars are less safe/less effective than reference products or that there may be clinically meaningful differences b/t them when biosimilars can’t be approved unless there are no clinically meaningful differences. Even absence of explicit falsity can be misleading overall and potentially harmful to public health by series of statements each true on its own but misleading overall in combination w/omissions. Seen this before w/Hatch-Waxman w/communications about generics suggesting they were outdated or less effective.

Dominic Cirincione, Regulatory Counsel, Office of Prescription Drug Promotion, CDER,
FDA: Fair balance is required in labeling/ads. FDA relies on statutory authority to regulate labeling/ads. OPDP: Surveillance/communication program, including response to voluntary requests for comment on draft materials; industry guidance; social science research program (researches issues on DTC and advertising to physicians—learn about studies on their website); review of disseminated materials/ “BadAd” program/warning or untitled letters; work with DOJ to pursue enforcement actions.

Common issues observed by OPDP in prescription drug ads & promotional labeling: omission of risk; minimization of risk; overstating effectiveness (unsupported claims/misrepresent data from clinical studies); misleading drug comparisons (e.g., comparing two different studies that may have different patient populations or methodologies). Warning letters 2015-2020: omissions/minimization of risk are largest share of letters, but false/misleading comparative/benefit claims are also taken seriously.

Richard Cleland, Assistant Director, Advertising Practices, Bureau of Consumer Protection, FTC: FTC covers only commercial speech. Looks to content (promoting demand for a product/service or denigrating competitor’s product; specific product references; information about type, price, quality or other attributes, including health benefits); means used to publish the speech (would it be recognized as advertising); and speaker’s economic motivation for disseminating speech. Peer reviewed scientific article or press release may or may not be commercial speech depending on how disseminated/used.

Falsity/misleadingess is covered including failure to disclose that is misleading. Companies are responsible for both express and implied claims. Net impression is what matters, to a reasonable person in target audience. Thus net impression may differ as between an ad targeted to a diabetes patient or a doctor treating diabetes. Reasonable consumers don’t read an entire ad; a footnote will rarely alter the net impression. Reasonable doesn’t have to mean majority; if a significant number of consumers would take a message away then the advertiser is responsible for that message.  Can be liable for misleading interpretation even though a nonmisleading interpretation is possible. A consumer might interpret the use of “not interchangeable” in a misleading way—to mean that a biosimilar couldn’t be prescribed in place of the reference product.

Specific claims: clinically meaningful differences b/t reference product & biosimilar; “there’s still a chance the patient may react differently”; claims about greater safety of reference product. Could all be false, unsubstantiated, and failing to disclose material information.

FDA Draft Guidance for Industry: Promotional Labeling and Advertising Considerations for
Prescription Biological Reference and Biosimilar Products Questions and Answers

Catherine Gray, Staff Director, Office of Prescription Drug Promotion, CDER, FDA

Elizabeth Pepinsky, Health Science Policy Analyst, Office of Prescription Drug Promotion,
CDER, FDA: Draft guidance issued by OPDP in consultation w/other groups focusing on biosimilars. The basic rules are the same: truthful and nonmisleading, risk/benefit balance, and disclose material facts. Companies should specifically identify the product/products to which the information applies: e.g., if it applies to reference product & biosimilars, say that; if promo materials use studies referencing non US licensed comparator, then that status should be accurately identified in the materials.  If presenting info from studies on reference product that are relevant to conditions of use for biosimilar, should refer to biosimilar’s FDA-approved labeling for information about the biosimilar. Data from studies conducted to support biosimilarity that aren’t included in the FDA-approved labeling should, if presented, be truthful, nonmisleading, and consistent w/FDA-approved labeling. Statements implying superiority where the differences in adverse reactions are not clinically meaningful would be misleading. Individual statements of accurate information could contribute to a misleading presentation when provided in comparative context. E.g., if biosimilar is licensed for fewer indications than reference product, a comparative presentation suggesting less safety in the licensed indications would be misleading.  

Dominic Cirincione, Regulatory Counsel, Office of Prescription Drug Promotion, CDER,
FDA: Examples of presentations that conform w/guidance. Scenario: promo materials say that one drug in a clinical study had a numerically higher overall response rate than another drug, but it’s not clinically significant: touting the numerically higher response rate would be misleading. Looking forward to stakeholder input on draft guidance, especially about how to convey interchangeable information.

Pepinsky: keep net impression in mind: individual claims aren’t enough to be nonmisleading about safety and efficacy, not just for comparative claims but for all claims.

What’s at Stake?  The Benefits of Competition
Alison Falb, Regulatory Counsel, Office of Therapeutic Biologics and Biosimilars, CDER, FDA 

• Murray Aitken, Executive Director, IQVIA Institute: Many dynamics in market. Biologics=growing share of market with significant growth over 5 yrs relative to small molecule. 42% of total medicine market by price in 2018, up from 30% in 2014; represents almost all of the growth; adjusting for inflation and population growth/per capita spending, small molecules declined 12% while biologics increased 50%. R&D pipeline suggests growth will continue across most disease areas, including those traditionally based on small molecules. Reach market through multiple channels & pay times, each w/own payment dynamics, including private insurance, Medicare types (both pharmacy and physician provided), Medicaid (ditto), fee for service, cash, commercial office/physician sites. Different incentives, reimbursement levels for each segment. Largest originator brands have significant sales since launch: each of the top 10 has cumulative sales of over $40 billion since launch, on market more than 17 years.

About 40% of small molecule market sales are accessible to generics. By 2019, 17% of biologics market is accessible to biosimilars, which have 20% market share. Including approved but not launched, 50% of biologic market sales could face biosimilar competition (that won’t happen until 2023 at the earliest).

[I think] David R. Schmidt, Assistant Director, Applied Research and Outreach, FTC  It’s early days for biosimilars, and early to be analyzing these markets. Look at whether different payors (and dispensing location) are treating biosimilars differently from the small molecule drugs those payors handle.

Andreas Schick, Director, Economics, Office of Program and Strategic Analysis, CDER, FDA: Also lessons in comparing different biologics. W/generics, we don’t see wide disparities by payor type. Reasonable to think that there shouldn’t be. Would be concerned if saw very different behaviors in Medicaid and non-Medicaid markets.

• Inma Hernandez, Assistant Professor of Pharmacy and Therapeutics, University of Pittsburgh School of Pharmacy: W/o interchangeability, we can’t pay for biosimilars the way we’ve been paying for generics.  Discounts are proprietary so we have trouble knowing what payors actually pay. Have some data from SSR Health; calculating average revenue for unit of product, net of discounts including rebates and other discounts including cards given to patients. Can separately estimate for Medicaid and other payors. Have showed robustness of data in paper in JAMA. One example of biosimilar entry: List and net prices increased in parallel until 2013; net prices started to decrease in 2015 when competition began, driven by increasing discounts to payors other than Medicaid. Another three examples: similar story, sometimes net prices begin to drift down before entry. Sometimes there are factors other than biosimilars (here: in-class competition by non-biosimilar drugs), also including public pressure over insulin prices for one of the examples, insulin glargine. List prices stagnated after competition, but net prices decreased due to discounts.  Unclear whether decreases related to number of biosimilars or only number of years post-biosimilar entry.  

What about rebates for drugs covered under Medicaid managed care organizations, collected by states pursuant to ACA? Market share of Basaglar (biosimilar to initial version of insulin glargine) is basically zero unless states have MCOs with no preferred drug lists (there are several other possible models). Preferred drug lists prevented uptake by listing it as non-preferred; results reflect strong financial incentives of rebates. More states are implementing preferred drug lists, so this is a timely result.  Competition is happening in discount, not in list price.

Comment by someone: seeing very different behavior for reference products in biologics space v. responses to generics in small molecules.

Aitken: we should get beyond saying they’re different from small molecules and say that fee for service Medicaid is different from managed care Medicaid and so on.

Alex Brill, Resident Fellow, American Enterprise Institute: Barriers to competition can be good and bad, big and small. Barriers to biosimilar entry: some are appropriate to protect innovator/producers and consumers (patents, exclusivity periods, approval process); others thwart healthy competition. Barriers to biosimilar utilization once entry occurs are uniformly bad. Bad barriers: myopic contracting practices by payors that discourage maturing of biosimilar marketplace; rebate traps; frivolous late-stage patents; inadequate physician and patient education not comparable to education that has taken place for small molecule generics.

Undue barriers to biosimilar entry/utilization: extends excessive monopoly rents; higher patient cost; less biosimilar discounting; fewer biosimilar competitors. Uncertainty associated w/ the viability of the market is a barrier: uncertainty of reference product price; legislative/legal/regulatory uncertainty; competitor biosimilar behavior—many of these are natural in a free market and will resolve over time w/experience, but we can strive to mitigate them. Exclusivity periods are specific and clear w/clear duration; patent thickets lack predictability. Regulators should try to minimize costs related to approval. Should be willing to incentivize participants to stop waiting—manufacturers, prescribers waiting for more information. Worth considering goosing the system to get over initial hurdle.

Improving Stakeholder Engagement:  Education and Understanding

Sarah Ikenberry, Senior Communication Advisor, Office of Therapeutic Biologics and Biosimilars, CDER, FDA
FDA has health care provider materials/fact sheets. Biosimilar basics for patients. Working on additional materials. Highlights similarities of biosimilars and reference biologics, benefits of increased access; urges patients to find out more from doctors/FDA. Going to create fact sheet for health care providers to address misconceptions, as well as teaching resources for medical/pharmacy/nursing schools.
Elizabeth Jex, Attorney Advisor, Office of Policy Planning, FTC

• Cheryl Koehn, Founder & President, Arthritis Consumer Experts: emphasizes importance of disclosure of material connections. Patients have seen white noise about safety/efficacy/lack of identicality/lack of interchangeability from originators: contributes to nocebo effect. Nocebo effect is real. Negative words, body language, subtle or not-so-subtle words are import and strategically deployed. Canada is ahead in switching: several provinces have switched most patients to biosimilars, with about 1% requesting exemptions and 1% granted. Can buy a lot of health care for $2 billion Canadian.

• Sameer Awsare, Associate Executive Director, The Permanente Medical Group: 12 million patients, $8 billion on pharma. Business model for drug use management is predicated on ability to move market share. Leverage exists b/c KP can deliver more than 90% of given market in short time; 12.2 million members are aout 4% of covered lives. Physician & pharmacist driven drug selection allows KP to promise & deliver, moving market w/99% physician compliance. Education of physicians & pharmacists with general biosimilar education; biosimilar data; then were able to show that KP patients did well. 80% of KP patients using Remicade successfully switched to biosimilar Inflectra; used medical records to guide the switch and to show outcomes. Found no increased risk of disease worsening in IBD patients switched to Inflectra. Similar experiences w/two other biosimilars. Once doctors were comfortable with the first biosimilar they were more willing to switch to others.

• Michele Andwele, Editorial Director for Health Content, Arthritis Foundation: key concerns: effectiveness? Could switching from reference product make me flare up? Are they safe? Will I pay less? Can a pharmacist substitute w/o doctor’s approval?  One patient: I pay $35/month; don’t have a financial incentive to switch if it’s working for me.  Language matters: inconsistent terminology use/unconscious bias in communication w/patients. Need provider consensus/patient advocacy group consensus on how products are described. Provider concerns: time constraints in discussing biosimilars in short time w/patients who may have many issues. Insurance coverage/patient assistance programs are issues; liability exposure in absence of interchangeability designation.  Educational initiatives shouldn’t be influenced by industry; learn from partners in Canada and Europe.

• Hillel P. Cohen, Executive Director, Scientific Affairs, Sandoz (trade group rep for Biosimilars Forum): has seen several types of disparagement. Information that is technically correct but omits info; negative framing of factual statements that matters to consumers. Sometimes factually incorrect claims. Safety, quality, and regulatory messages. E.g., efficacy is not fully proven, or may not be as good as the reference product. Seen comments about extrapolation: some doctors/patients say extrapolation is inappropriate. Seen safety not fully proven, or potential for more bad effects. Switching: there are comments that we don’t have enough data to conclude that switching is safe, implying that it may be unsafe. Doctors can already prescribe the appropriate product; you don’t need interchangeability for that. Quality: that it may not be the same as the reference product/it’s only similar or highly similar, not identical, even though differences aren’t clinically relevant—that’s difficult to understand. Statements that interchangeability is a higher standard, implying that biosimilars are of lower quality than interchangeable biologics, even though they are structurally identical. Regulatory pathway has created some of the problem: “abbreviated” pathway. Some people say it’s not as rigorous as pathway for reference products, despite rigor.

Recommendations: truthful & complete information should be required. Positive framing of benefits; easy to understand messages. Messages should be based on FDA documents but tailored to their audiences. Large orgs and patient advocacy groups have done the research and are on board w/biosimilars, but the average patient is not knowledgeable. Need to educate them, via educating physicians—rheumatologists know more than gastroenterologists right now.  FDA should prevent disparagement/misinformation. Incorporate biosimilar education into educational curriculum for doctors, nurses, pharmacists. Patient groups should disclose funding & conflicts of interests—it’s fine to speak your positions, but full disclosure is important.

Koehn: on language, biosimilars are biologics; if you use two different terms people think they’re not the same thing.

Andwele: Also need an influencer strategy: patients as peers.

Cohen: highlight the rigor of the process used to approve the biosimilar. Sound scientific policy. Doctors are used to clinical trials; it’s a different methodology, but does assure safety & efficacy. Coordinated effort w/professional societies and patient groups is necessary.

Andwele: message segmentation. Treatment-naïve patients v. someone stable on a biologic.

Biosimilar Disparagement as an Antitrust or Consumer Protection Cause of Action
• Richard Cleland, Assistant Director, Advertising Practices, Bureau of Consumer
Protection, FTC
• Randall Weinsten, Attorney, Health Care Division, Bureau of Competition, FTC

Michael A. Carrier, Distinguished Professor, Rutgers Law School: statements like “we need to proceed cautiously so we don’t end up with another thalidomide, or all the things that happen when safety isn’t considered”; claims that it would disrupt continuity of care/could put patient in ER/could bring patient out of remission. Not appropriate given definition of biosimilars.

More subtle: claims that the biosimilar is not identical to, or acts differently from, reference product. Pfizer citizen petition contains many claims: it’s not just apples to apples; patient may react differently. Genentech says: the FDA requires highly similar but not identical. FDA is good at taking on these misrepresentations.

Another category: interchangeability. There are some intimations that not interchangeable = not meeting highest standards of safety & efficacy.

Most subtly: company says the drug acts “similarly.” Jansen says “you may be asked to switch to a drug that acts similar to Remicade.”  FDA’s guidance addresses that.
Rebecca Tushnet, Frank Stanton Professor of First Amendment Law, Harvard Law School 
Elements of a Lanham Act claim: key elements are falsity or misleadingness, materiality to a reasonable consumer’s purchase decision, and likelihood of harm to the plaintiff.

Mostly unique to the Lanham Act cause of action, compared to an FTC or state consumer protection law claim: the sharp doctrinal difference between false and misleading claims. Although both falsity and misleadingness are actionable, the burden on the challenger is much greater if a claim is misleading than if it is literally false. That puts a premium on distinguishing falsity from misleadingness. How does a plaintiff establish a claim is false? Courts ask: What is the explicit meaning of a claim. Once you know the explicit meaning, you can then determine whether that factual claim is false. However, sometimes courts are willing to make general inferences from disparagement. Also important to distinguish lay audiences and expert audiences: dictionary meaning may not be as important as what people are likely to understand.

How does a plaintiff establish a claim is misleading? Relevant when the claim is ambiguous and has potentially true and potentially false meanings; the question is what message reasonable consumers receive. Usually through surveys of the relevant consumers. If 15% or more of consumers, net of control, receive a false message, then P is likely to prevail.

When is empirical evidence of consumer reaction necessary? Not in literal falsity cases; literal falsity is presumed to reach a substantial number of reasonable consumers. Basically always required in misleadingness cases. [Intent, direct testimony from deceived consumers as possible but unlikely substitutes] 7th Circuit case, Eli Lilly v. Arla Foods (2018): Eli Lilly sued over images portraying rBST, a hormone given to cows to increase milk production, as a scary toothed monster with electric fur. The 7th Circuit finds there’s no literal falsity, but still affirms an injunction: “The use of monster imagery, ‘weird stuff’ language, and child actors combine to colorfully communicate the message that responsible consumers should be concerned about rbST-derived dairy products.”

Impact of First Amendment: Courts have generally said that the Lanham Act false advertising cause of action raises no constitutional issues because by definition it targets only false or misleading commercial speech, which can constitutionally be banned.

According to Supreme Court doctrine, when it comes to direct gov’t regulation of speech, there is a distinction between inherently or actually misleading v. potentially misleading: Whether the speech can just be banned or whether instead a disclosure must be added to try to draw the sting of the misleadingness. This isn’t well worked out and has largely been done by courts guessing, or worse, about what’s inherently or actually misleading versus correctable and only potentially misleading. Much room for presenting courts with facts about misleadingness.  Not the same distinction as is made in Lanham Act cases, where misleadingness is grouped into one category distinct from falsity.

Relationship between private and public enforcement: Courts in private litigation often defer to the FDA’s factual findings about what is true but without a lot of explanation about why they’re deferring.
First Amendment may also bear on the question of de novo review of agency determinations: what are the medical facts versus what are consumers’ perceptions of the messages they receive?  The former—the facts of safety and efficacy—may as a practical matter receive more deference than agency determinations about misleadingness, even though both are subject to ordinary mechanisms of proof.

Q: role of consumer protection claims?

RT: likely to be limited b/c of barriers to class actions.

Cleland: POM case: DC Circuit said deceptive = no First Amendment protection. Should go into relief ordered, not into whether it is actionable.

RT: agree, but courts are often not great at signaling their order of operations.

Cleland: materiality to competitors?

RT: to consumers, which then affects competitors when consumers’ decisions are affected. [in response to Q] Could be patients or doctors; both have substantial influence on what drugs are prescribed.

Carrier: monopolization claims: these are highly concentrated markets, w/few substitutes. Liability requires monopoly power + exclusionary conduct. Some courts have rejected any liability for disparagement; others have made it very hard/impossible to find liability; others say it’s case by case. In the first bucket, 5th & 7th circuits say that false advertising is pro-competitive by increasing competition in the market for advertising. This is nonsense. It’s at least possible to get/maintain monopoly power by disparaging rivals. Rivals can’t fix it; can have significant effect on overall market.

Second approach: de minimis rule: assumes disparagement is de minimis without a showing of lots of things: clearly false, clearly material, clearly likely to induce reasonable reliance, made to buyers w/o knowledge, continued for prolonged periods, not subject to neutralization. The bar is just too high—taken from leading Areeda/Hovenkamp treatise. Was adopted at a time when the standards for false advertsing weren’t clear. There are a lot of instances of false advertising that aren’t monopolization, but false advertising in a monopoly context can harm markets.

Clearly false: you can have deceptive statements even if they aren’t clearly false, as has been delineated here. That standard is too high.  Clearly material: yes, deals with safety/health; would induce reasonable reliance for that reason. Knowledge of subject matter: the drug companies have better knowledge. These drug monopolies go on for years. It’s hard to neutralize: biologic company says “you could go to the ER” and that’s tough to rebut.

Third bucket: case by case approach of 3d, 8th, and DC. False statements can be so unfair as to constitute an unreasonable restraint: e.g., does it lock in decisionmaking? Does it make it harder for competitor to get financing? Hard to get financing if you’re subject to claims about safety/efficacy. Relevant also: the regulatory setting. Wonderful to see FDA/FTC working on this, but the agencies might not be able to solve the problem on their own. Drug companies think it’s in their bottom line interest to get away w/slap on wrist, maintain monopoly power. Role for courts to police barriers to entry, especially given other barriers to entry like trade secrets, patent thickets, etc. Bundling existing and new patients makes it harder for new patients to get the biosimilar.

Weinstein: do we need private antitrust enforcement?

Carrier: we need all three: private antitrust, false advertising, and regulatory enforcement. No matter what agencies can do, bad actors may be able to cross the line and commit antitrust violations. The benefit is that it focuses on market effects: increased price, reduced output—antitrust is uniquely able to deal with that. It has treble damages, attorneys’ fees, injunctions: it can consider all kinds of anticompetitive conduct in their full context and interactions. Suboxone: an overall course of conduct can violate the law. The companies aren’t doing just one thing, they’re pursuing many strategies.

Weinstein: would a consumer class action work here?

Carrier: courts aren’t always receptive, especially given the nuanced role of the misinformation here. FTC uniquely has §5 power to go after unfair/deceptive acts or practices, with more leeway than private antitrust.

RT: Right now some courts do a “heads I win, tails you lose” approach: Becton Dickinson in the 5th Circuit, P lost its antitrust claim because false advertising couldn’t affect the market in general, then lost its false advertising claim b/c it affected the market in general and P couldn’t show which of the sales it had lost v. its rivals.

Carrier: our forthcoming article (watch this space) lays out how you should think about presuming anticompetitive effect when false advertising is done by a monopolist. Our test applies to monopolists, and it doesn’t make all false advertising into an antitrust problem. We take the learning from false advertising law and apply it to antitrust: a well developed body of law.

We’d need to figure out what it takes to have real competition in biologics.

Q: how do you establish competitive harm? Is deception enough?

Carrier: for a biologic w/monopoly power, I think that’s enough. Biosimilars are injured; regulatory scheme is impaired b/c biosimilars are supposed to play a crucial role in lowering price. Competitor harm = consumer harm.

Q: belief that it would be hard to deceive prescribing physicians about safety/effectiveness. If true, is there still a role here for harm to competition?

Carrier: yes, b/c we have a price disconnect. Not like any other market where price/quality determination is made by any one party. Doctors, payors/insurers, consumers: lots of room for anticompetitive conduct w/r/t patients and pharmacy benefit managers.  Pharma gives us whack a mole all the time: every time you think you’ve figured out what is going on, there’s something else. Gilead case: new combination of settlements and product hopping we haven’t seen any more. Transferred patents to Native American tribe to try to avoid PTO review. This is just the next stage in that process of invention. Antitrust is well equipped to deal w/variety of shenanigans.

Q: rulemaking as a possibility. Comm’r Chopra wants more FTC rulemaking.

Carrier: may well be useful. Yes to rulemaking and yes to enforcement in the courts. Could shed light on the problem, as does the guidance FDA has offered. Make clear you can’t hide behind clear falsity: deception/misleadingness is a problem. 

Q: gov’t v. private actors?

Carrier: sometimes this conduct is nuanced. Safety intimations; an ideal recipe for FTC action.

RT: at some point companies should step up and go to court to defend their own interests if they’re losing millions. But public harm also matters and can justify gov’t intervention. Antitrust prides itself on its hard-headed empiricism but the majority tests presently ignore all the learning we have about false advertising’s effects. That should change.

Carrier: Pfizer is suing J&J; it is possible, b/c entering the market w/ a biosimilar requires lots of resources.

Open Public Comment  
• Sarah Ikenberry, Senior Communication Advisor, Office of Therapeutic Biologics and Biosimilars, CDER, FDA 
• Eva Temkin, Acting Director for Policy, Office of Therapeutic Biologics and Biosimilars, CDER, FDA 
• Catherine Gray, Staff Director, Office of Prescription Drug Promotion, CDER, FDA
• Antara Dutta, Economist, Bureau of Economics, FTC 
• Armine Black, Attorney, Health Care Division, Bureau of Competition, FTC

Juliana Reed, Pfizer/ Biosimilars Forum: continued problems of misleadingness, but that’s not the only barrier.

U Pitt pharmacy school professor: Europeans are fine prescribing biosimilars b/c of nearly 2 decades of experience. Physician confidence is high uniformly but uptake varies by country, which probably reflects other factors including payor practices. Health care practitioners in the US are also not skeptical; they are enthusiastic about biosimilars.

Marilyn Feldman, Alliance for Safe Biologic Medicines: rheumatologists were willing to prescribe, but clinicians are often hesitant to change b/c it can take years to stabilize a patient. And they’ve become sensitized to non-medical changes based on formularies that have changed patients’ medicines every 6 months in order to make higher profits. They even switch patients to completely different biologics. So doctors are leery of a great switching experiment. Biosimilars are behind the 8-ball because of financial incentives. Incentives that benefit the physician can undermine trust in doctors. Considering the perception that US lags behind Europe, 5 years out there were 11 products but we have 26: FDA deserves thanks for building out approval so quickly.

Sundar Raman [sp], biosimilar company: Data for biosimilarity should also suffice for interchangeability; no more is required and practically they are already interchangeable. But the difference allows anticompetitive behavior by originators, including misrepresentations and payment practices.

Andrew Spiegel, GCCA, Alliance for Safe Biologic Medicines: Unaware of any attempt to undermine confidence of patients & doctors in biosimilars. Patients & providers have accepted biosimilars as part of health care.

Kim Caldwell, pharmacist, PCMA (pharm benefit manager ass’n): 270 million Americans in covered plans. Patent thickets are bad; product substitution is good—should lower barriers to substitutions. Patients & clinicians may be uncertain about switching/substitution.

Andrew Greenspan, Jansen Pharm./J&J: patients should have data on alternating before that happens; implying that alteration/interchangeability is fine for a biosimilar is misleading w/o data. Some molecules are more immunogenic than others; patients may face switching every 6 months and need good info.

Ad compliance guy: Dr. Google is often the driver of patients to particular sites. FDA Warning letter last month specific to search ads on Google: request that final guidance documents specifically get into how biosimilar guidance applies to marketing platforms w/character space limits, and to brand-connected ads: ads that don’t mention a brand themselves and then link directly to a brand website.

Rheumatologist: hasn’t seen disparagement in educational materials, offices, etc. Don’t believe that’s responsible for impaired patient access. The access problem, which exists, lies elsewhere. Manipulations designed to maximize profits from fees, rebates, and other schemes. Don’t address those and access won’t happen; far outweigh the effects of deceptive marketing. Formulary decisions are rarely if ever based on medical outcomes. Overly consolidated industry of unregulated middlemen with unfettered power demanding ever increasing tolls from patients and pharmacos. Major driver of rising costs. Should not be allowed to continue. Insurers, large pharmacies, and PBM conglomerates are main barriers to access for biosimilars and indeed all pharmaceuticals.

Laura Brandt (sp), Amgen: US market is emerging but robust; the current market structure is good.

Andre Barlow (sp) on behalf of Coalition to Protect Patient Choice: highlights the role of rebate walls: agencies should prohibit rebate policies that block biosimilar competition. Such policies raise the cost of drugs overall. Go to PBMs rather than consumers; perverse incentives to negotiate higher list prices, requiring higher coinsurance payments from patients b/c of higher list costs. Rebate wall/trap: use existing market power to secure formulary access w/volume based rebates on condition that they deny formulary access to rival drugs, bundled across drugs for many conditions that can’t be matched by new entrants—even if the biosimilar is offered at greater discount or for free. Most PBMs require patients to fail first on the more expensive branded drugs, instead of the historical fail first on generic requirements. Step therapy rules used to foreclose competition.

PhRMA rep: Physician education is good. Meaningful rebate reform would promote access and competition.

Corey Greenblatt (sp) Global Health & Living Foundation: nonprofit for chronically ill patients. Pricing is the key. Nonmedical switching needs to be defined; patients/doctors should be able to nonmedically switch when it benefits them, not when it benefits the PBM. Forced nonmedical switching only profits PBMs/insurers. Patient is the only one who shows up w/a checkbook and no power. You can change this by strictly regulating insurance practices & creating market incentives for uptake.

Laura McKinley, Pfizer: Should be able to extrapolate for additional indications even in the absence of clinical data, speed up approvals. Biosimilar exclusion contracts withholding rebates for both current and future patients exclude biosimilars. Prevents doctors/patients from trying biosimilars.

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