Amarin Not Giving Up On Omega-3 Trade Battle

Amarin asks Federal Circuit Court to direct US ITC to investigate its complaint that some omega-3 ingredients are unapproved drugs. Company questions FDA's request for policy deference given resource constraints and says Supreme Court rulings show compliance with FDA regulations in cosmetic and food labeling does not preclude litigation alleging the information renders a product an unapproved drug or represents false advertising.

Amarin Corp. PLC continues to wage its battle to force the International Trade Commission, or perhaps FDA, to decide explicitly whether some products marketed as dietary supplements unfairly compete with its ethyl-ester eicosapentaenoic acid omega-3 drug,

Amarin had asked ITC to investigate its complaint that the imported supplement products may violate fair trade rules. ITC recently declined to undertake such a review. Information submitted for ITC's consideration included FDA's advice that such evaluations are in FDA's purview, not the trade panel's.

The company now has submitted a petition to the US Circuit Court of the Federal Circuit, asking it to order an ITC investigation. Among its arguments in the Dec. 1 petition, Amarin questions FDA's position, given that the agency's acknowledged lack of sufficient resources to effectively regulate the supplement market may prevent it from reviewing all industry concerns. Amarin also says FDA in effect usurped ITC's own authority.

"When manufacturers incorrectly decide that a drug is a dietary supplement, FDA can only police the purported dietary supplement’s lack of compliance with the [Food, Drug and Cosmetic Act] by relying on enforcement actions, warning letters, and other measures taken after a product is brought to market. Because of limited resources, however, the agency cannot pursue every violation," according to Amarin, which markets Rx drug Vascepa (icosapent ethyl), a synthetically produced ethyl-ester eicosapentaenoic acid (EPA) omega-3 indicated to reduce triglyceride levels in adults with severe hypertriglyceridemia.

Amarin Rx drug Vascepa (icosapent ethyl), a synthetically produced ethyl-ester eicosapentaenoic acid omega-3 indicated to reduce triglyceride levels in adults with severe hypertriglyceridemia.

The FDCA prohibits private actions to enforce FDA regulations. But this should not stop ITC "from applying or interpreting the act when private parties invoke rights of action under other statutes," such as advertising and trade regulations, Amarin's also says in its petition for a writ of mandamus – an order to compel a judicial or government officer or agency to perform a duty. "Competitors do not have an open field to engage in unfair trade practices like falsely labeling unapproved drugs as dietary supplements merely because FDA lacks the resources to enforce the FDCA against every violator."

Amarin's petition was authored by company counsel and attorneys with King & Spalding LLP in Washington. The Dublin-based firm's original ITC complaint targets synthetically produced omega-3 oil as dietary supplement ingredients or as finished products or encapsulated synthetically produced omega-3 oil with purified EPA or omega-3 fatty acid mixtures that are predominantly EPA in ethyl ester or re-esterified form. It argues that before these types of omega-3 fish oils were used as dietary ingredients they were the subject of investigational new drug programs, precluding their use as dietary ingredients under FDA regulations for supplement manufacturing and marketing. (Also see "Omega-3 Drug Firm’s Trade Complaint Questions US Dietary Ingredient Standards" - HBW Insight, 5 Sep, 2017.)

FDA advised ITC should not investigate Amarin's complaint, saying the firm was asking the commission to do FDA's job by deciding whether certain omega-3 supplements are unapproved drugs. FDA asserted that its expertise is needed to determine the answers Amarin seeks and suggested that the firm could file a citizen petition with FDA asking for the determination. (Also see "FDA Objects To Amarin Trade Complaint Against Omega-3 Ingredients" - Pink Sheet, 11 Oct, 2017.)

ITC, an agency of the Department of Commerce, announced late October it would not open an investigation, saying Amarin did not allege an unfair method of competition or an unfair act by the 18 omega-3 supplement marketer and ingredient providers it had identified as proposed respondents. (Also see "Trade Panel Bolsters FDA's View In Amarin Omega-3 Complaint" - Pink Sheet, 30 Oct, 2017.)

'Facing Unfair Competition'?

In its request to the Federal Circuit, Amarin repeats a plea about unfair competition stated in its ITC complaint, that its litigation is aimed at protecting its competitive interests for Vascepa. The firm also filed a separate petition asking the Federal Circuit, in the event it does not order ITC to investigate its complaint, to review the commission's decision dismissing its request.

"When Amarin brought Vascepa to market, it made the significant investments needed to comply with US law and sell its product as an FDA-approved drug. The company is now facing unfair competition from a small group of omega-3 products that are in reality unapproved, imported drugs that are being falsely sold and deceptively described 'dietary supplements'," the petition states.

"Competitors do not have an open field to engage in unfair trade practices like falsely labeling unapproved drugs as dietary supplements merely because FDA lacks the resources to enforce the FDCA against every violator." – Amarin petition to Federal Circuit

During the firm's third-quarter earnings briefing in November, Amarin General Counsel Joseph Kennedy also described the litigation's impetus and purpose, saying some omega-3 supplement marketers "synthetically alter their products to concentrate the EPA in the fish oil and the [docosahexaenoic acid] in the fish oil to get a higher level of efficacy."

"As we look back at the regulatory scheme and FDA's interpretation of that, we believe that those products should be classified as drugs under the regulatory scheme. So, we see those products as essentially competing in a way that's unfair," said Kennedy, who also is Amarin's chief compliance officer and executive vice president of strategic initiatives.

The Global Organization for EPA and DHA (docosahexaenoic acid) Omega-3s trade group says the market for the supplements and FDA's regulation of the products have not changed since the ITC complaint was rejected.

"We feel that if ITC was ordered by the courts to institute an investigation that the Commission would ultimately find that it is acceptable for concentrated EPA and DHA products to be sold as dietary supplements. The core issues at the center of the case have not changed," said GOED President Adam Ismail.

Amarin's ITC complaint doesn’t challenge the adequacy or effectiveness of FDA regulations for supplement label claims or for determining whether an ingredient is safe for use in a product, but it raises general questions about using synthetic dietary ingredients in supplements and about application of the regulation that prohibits substances previously identified as IND candidates from use as dietary ingredients.

ITC Mandated To Investigate?

FDA contended that Amarin asked ITC to do the drug agency's work, but the firm argues that the commission is required by federal advertising and trade regulations to investigate its complaint.

"Nothing in Amarin’s complaint requires the commission to enforce the FDCA or resolve any issue that would require scientific expertise," and ITC's "non-institution decision constitutes a clear abuse of discretion," according to the petition.

A mandamus is warranted because the Sec. 337 of the Tariff Act, which prohibits unfair acts and unfair methods of competition involving imports, "mandates that the Commission institute an investigation where, as here, a complaint’s properly pleaded allegations raise claims within the commission’s jurisdiction" and ITC's "reasons for not instituting an investigation rest on a clear misunderstanding and violation of controlling precedent," the petition states.

No 'Administrative Leeway" For ITC?

Amarin's attorneys argue that ITC decisions against investigating fair trade complaints are rare for multiple reasons, one being that the Tariff Act says the commission "shall" investigate any alleged violation. "The statute provides no room for administrative leeway," the firm contends.

The petition point outs the Federal Circuit in previous rulings "has likened 'shall' in this context to 'the language of command,' necessitating 'strict compliance' and permitting termination of an investigation only in statutorily defined circumstances, 'interpreted narrowly'.”

Similarly, the Supreme Court also has said that when a statute uses “may” and “shall” in different provisions, “'shall' denotes a 'requirement' and 'imposes a mandatory duty' on the agency," according to the petition.

Although the Sec. 337 Tariff Act also uses "more permissive language" in defining ITC's obligations, Amarin's complaint does not fall into any area that allows the commission not to investigate, the petition says.

Additionally, ITC data and a professional group's observation show that the commission's "historic practice confirms that the statute means what it says," according to the petition. The commission, which does not disclose statistics on cases it has declined to investigate, says its decisions "not to institute an investigation are rare.”,

Research shows that of the far more than 1,000 Sec. 337 complaints filed over the past 20 years, ITC " declined to institute an investigation in only a small handful," and the ITC Trial Lawyers Association says, "Only in extremely rare circumstances does the ITC decide not to institute an investigation,” Amarin says.

Additionally, Amarin argues its allegations are not among the "few specifically enumerated and narrowly drawn exceptions to the commission’s mandatory obligation to institute an investigation" fair trade complaints. One exception is for complaints that allege violations of antidumping and countervailing laws, an exception identified in US trade law. Another exception has been recognized in court rulings for "unique circumstances" of allegations "so inadequate that they do not provide a sufficient factual basis for the commission to take action."

Moreover, ITC "did not identify any allegations lacking sufficient information or give Amarin an opportunity to re-file its complaint," the petition adds.

Instead, Sec. 337 "imposes a mandatory, non-discretionary duty on the Commission to institute an investigation where, as here, it is presented with a complaint under oath," Amarin argues.

Amarin also litigated in 2015 to help boost Vascepa sales with a suit challenging FDA's regulations on off-label drug promotion and seeking a determination that it could communicate to health care providers information from studies on the drug's use as statin therapy for high triglyceride levels. It argued that FDA permits supplement manufacturers to make claims that omega-3 fatty acid products “may” reduce the risk of coronary heart disease and EPA “lowers triglycerides,” but forbids the firm from telling doctors that in studies Vascepa lowered triglycerides for patients with persistently high levels in studies.

A judge ruled Amarin could engage in truthful and non-misleading speech about the unapproved use of Vascepa in patients with persistently high triglycerides and that such speech may not form the basis of a misbranding lawsuit. The firm and FDA settled in an agreement that included an optional preclearance process for the company's future communications about off-label use of Vascepa.

Another strategy Amarin has exercised to promote Vascepa sales was a 2015 survey it sponsored that showed doctors and pharmacists regularly recommend omega-3 supplements for patients with abnormally high cholesterol or triglycerides. It also raised questions about health care professionals’ knowledge of FDA regulation of supplement products (see sidebar).

Allergan, POM Wins Relevant?

The petition also tries to leverage two Supreme Court decisions that compliance with FDA regulations in cosmetic and food labeling did not preclude litigation alleging that the information renders a product an unapproved drug or that it represents false and misleading advertising.

Amarin notes the Supreme Court in 2015 declined to hear [Athena Cosmetics Inc.]'s appeal of the Federal Circuit's agreement with a lower court decision allowing drug firm Allergan Inc. to litigate a complaint that Athena's RevitaLash prostaglandin-containing products compete unfairly with its Rx Latisse eyelash-growth treatment, which contains bimatoprost, also a prostaglandin. (Also see "Industry Roundup: Nicotine Exposure ANPR, Athena Petition Denied" - Pink Sheet, 6 Jul, 2015.)

By denying Athena's writ for certiorari, the court "rejected the view that only FDA had authority to interpret and apply the FDCA’s statutory terms and determine whether a manufacturer engaged in an unfair trade practice by improperly marketing an unapproved 'drug' as a 'cosmetic',” Amarin's petition states.

They also note neither FDA’s letter to ITC or the commission’s decision referred to the Federal Circuit's decision in the Allergan/Athena litigation.

In the second case, the Supreme Court in 2014 unanimously decided to overturn lower court decisions that rejected a complaint by [POM Wonderful LLC] and allowed FDA’s approval of labeling for the Coca-Cola Co.'s Minute Maid beverage as a “Pomegranate Blueberry Flavored Blend of 5 Juices.”

Similar to Amarin's allegation about certain omega-3 supplements, POM argued that Coke's advertising for the product violated Lanham Act prohibitions on false advertising. While Amarin argues that some omega-3 products are falsely labeled as dietary statements, POM targeted the Minute Maid drink because it contained 99% apple and grape juices and POM formulated its product with 100% pomegranate juice.

In ruling for POM, the High Court held that "'Congress did not intend the [FDCA] to preclude Lanham Act suits'” alleging false and misleading advertising, Amarin's attorneys say.

They point out that although the US Solicitor General argued in the POM/Coke proceedings that FDA rules are a “ceiling on the regulation” of labeling, the court said “'Congress intended the Lanham Act and the FDCA to complement each other' with respect to labeling.

Additionally, the attorneys argue that FDA’s letter to ITC "attempts to resurrect the same field-preclusion arguments that the Supreme Court rejected in POM Wonderful."

From the editors of the Tan Sheet.