Direct-to-consumer ads pump sales for some indications, flounder for others

Getting a drug through today's rigorous and costly development and regulatory processes – a 2014 Tufts study estimated more than a decade and $2.6 billion in expenses – might seem like the endgame. But the next step, getting that drug into the hands of doctors and patients, is just as crucial, and that's where a successful direct-to-consumer (DTC) marketing campaign could make the difference between a market leader and an also-ran.

Pfizer Inc.'s Lipitor (atorvastatin), for example, was the fifth statin to hit the market yet it blasted past competitors, thanks largely to an aggressive DTC effort that included the now-admittedly controversial ads featuring artificial heart inventor Robert Jarvik. The New York-based big pharma finally backed off DTC marketing for Lipitor in 2012 after the once top-selling drug hit its patent expiration, but Pfizer has capitalized on DTC for other drugs in crowded markets such as erectile dysfunction product Viagra (sildenafil citrate), pain drug Lyrica (pregabalin) and, recently, its Bristol-Myers Squibb Co.-partnered warfarin alternative Eliquis (apixaban).

Success has not come cheaply, however. In 2014, Pfizer spent a whopping $1.4 billion on DTC advertising, according to consultant firm Kantar Media.

Granted, Pfizer is at the extreme end of DTC spending. But even for firms with more modest campaigns, DCT advertising still represents a substantial investment. The television, print and website ads themselves are the obvious costs, but companies also have to bring on board teams to craft DTC campaigns that comply with all regulatory guidelines. Yet, despite the challenges, more and more companies are opting for the DTC route. Michael Roth, CEO of marketing and advertising firm Interpublic Group, recently toldAdvertising Age that ads for the health care sector marked his firm's fastest-growing area, with year-over-year growth of 13 percent.

Running a DTC campaign was not something Forest Laboratories Inc. had much experience with when it signed up as the commercialization partner for irritable bowel syndrome (IBS) drug Linzess (linaclotide), developed by Ironwood Pharmaceuticals Inc. The pharma firm (later acquired by Actavis plc) previously had concentrated on physician outreach.

"This is something they had never done before," said Tom McCourt, chief commercial officer and senior vice president of marketing and sales at Ironwood. But IBS with constipation, or IBS-C and chronic idiopathic constipation were indications that seemed ideal for reaching out to patients directly, with market research indicating a lack of awareness among many suffering from IBS symptoms.

"Working with [Forest], we ended up in a really good place." McCourt was speaking of consumer awareness, but the DTC efforts have so far paid off for Ironwood as well. In its fourth quarter earnings call in February, the Cambridge, Mass.-based firm reported that since the DTC campaign launched in April 2014, total weekly prescriptions for Linzess jumped by more than 20 percent.

"It's rare in the industry today when you see a direct inflection point when you launch" a DTC effort, he toldBioWorld Today. Typically, it's "kind of a slow grind over time, but this was literally within the first week or two."

J.P. Morgan analysts were impressed, too, including Ironwood as one of their top stock picks for 2015 in a January note. "We have been impressed with market metrics for Linzess (linaclotide) and the DTC campaign has clearly had a positive effect."

Directly targeting consumers, however, isn't always effective.

A campaign launched by Dendreon Corp. in 2013 aimed at educating the public on first-of-its-kind cancer vaccine Provenge (sipuleucel-T) was talked up by management, though many analysts were skeptical, some because DTC ads are unusual for oncology products and others because they saw the move as a case of too little, too late.

Ultimately, the effort failed to help, and Seattle-based Dendreon entered a deal earlier this year for its assets, including Provenge, to be acquired by Valeant Pharmaceuticals International Inc. in a stalking horse bid.

In 2012, seeing a slow ramp-up in sales of insomnia drug Intermezzo (zolpidem tartrate), Transcept Pharmaceuticals Inc.'s marketing partner Purdue Pharmaceutical Products LP committed to a six-month DTC program, with a targeted campaign including digital and print ads and television spots, all touting the product's niche indication in insomnia, specifically its rapid onset of action and short effect for middle of the night waking. (See BioWorld Today, Nov. 28, 2012.)

The move was short-lived. The following year, Purdue significantly cut back on marketing. Analysts' post-mortem cited a multitude of potential stumbling blocks: difficulty establishing middle of the night waking as a condition of its own in the minds of doctors, patients and managed care providers; and the fact that Intermezzo, though a different formulation, comprised the same ingredient as Ambien, which had by then gone generic.

CLOSE THE DIALOGUE GAP

It's not enough to simply decide to employ DTC marketing. Companies have to figure out who and where the patients are, how best to reach them and with what sort of messaging.

"It starts with understanding the patients, their needs, behaviors and understanding media habits," said McCourt, who, prior to joining Ironwood, served on commercial teams for Prilosec (omeprazole) as well as Novartis AG's Zelnorm (tegaserod maleate), the first IBS drug that was subsequently pulled from the market because of safety concerns.

Having launched DTC campaigns on multiple branded products during his career – "some worked well, some worked less well," he said – McCourt listed several tenets for deciding when DTC outreach is worth the investment. "Is there really clearly a population with an unmet need? Is it well defined by us, by physicians and in the minds of patients, and am I bringing a solution that provides incremental value?"

Having patients able to self-identify is crucial for the message to be effective, so indications most amenable to DTC ads are those that are highly symptomatic and are not fully relieved with available therapies.

"If you can identify a symptom, then you can own" that disease market, McCourt said. The drug ends up linked in the public consciousness with the symptom it's designed to treat. "That's a very powerful place to be. We learned that with Prilosec. That purple pill became synonymous with heartburn and GERD [gastroesophageal reflux disease]."

Cambridge, Mass.-based Ironwood is in a similar place with Linzess. "We had a solution here in Linzess that provided relief and efficacy [in IBS with constipation] that didn't really exist before, particularly in relieving abdominal pain," McCourt said. "Nobody really owned abdominal pain . . . so out of the gate, that's really what we wanted to focus on."

Interestingly, McCourt's experience taught that patients tend to self-identify with symptoms rather than the disorder itself. "We learned that with Prilosec," he said. "We call it GERD, but what we focus on is heartburn."

In IBS, especially, there's also likely a reticence among patients to self-identify with the disorder, given the psychosocial stigma, McCourt pointed out. "So patients are more comfortable talking about symptoms."

In cases where a disease is not particularly symptomatic, DTC efforts tend to be much less effective, as they are also in instances where the product's ability to resolve the symptoms lacks clarity. The most effective DTC ads are those that provide a common vocabulary that can facilitate discussions between doctors and patients.

Linzess marketing employs a similar message when it reaches out to physicians, McCourt added. So when a patient comes in and begins explaining symptoms, "they know exactly what the patient is describing."


KEEP IT SIMPLE


Some drugs are obvious shoo-ins for a DTC approach. Take Valeant's Jublia (efinaconazole 10 percent topical solution) for toenail fungus infections. Most patients likely don't know the medical term, onychomycosis, but they know it when they see it. Jefferies analyst noted in a March research report that the number of Jublia total prescriptions "continues to impress . . . and the drug's robust growth trajectory has been led by a strong DTC campaign."

In some cases, going straight to consumers might even be more effective than targeting physicians. In a January note following a meeting with Arena Pharmaceuticals Inc.'s management, Wells Fargo analysts pointed to partner Eisai Inc.'s shift in marketing strategy for weight loss drug Belviq (lorcaserin), which includes cutting the sales force from 600 to 450 reps. "Eisai's analysis suggests its DTC outreach (magazine/television ads, digital out-reach) are having a greater impact on Belviq use than its physician-targeting efforts," the analysts wrote.

Like those examples, many of the drugs that work best in a DTC approach are considered quality-of-life drugs, conditions that are considered more troublesome to patients than to physicians. That said, other indications have resulted in effective marketing efforts such as flu treatment Tamiflu oseltamivir phosphate, Roche AG) and chronic obstructive pulmonary disease (COPD) product Breo Ellipta (fluticasone furoate/and vilanterol, Glaxosmithkline plc). The key is that both the disease and the solution can be expressed in a simple, concise and memorable message.

The television spot for Linzess, for instance, which Ironwood's McCourt refers to as the "belly ad," features an abdomen with an illustration describing a stomach tied up in knots, with the knot unwinding after treatment with the GC-C agonist. That ad had "great stopping power, but it also delivered a very simple message," he said.

Other good examples using clear visuals include ads for Boehringer Ingelheim GmbH's Spiriva (tiotroprium), in which COPD is described as an elephant sitting on a patient's chest, and for Astellas Pharma Inc.'s overactive bladder drug Myrbetriq (mirabegron) featuring a woman stalked by oversized animated bladder as she attempts to go about her day.

Especially in a crowded or established market, where the goal will be convincing patients to switch from one medication to another, the message itself has to be memorable.

Meanwhile, some DTC campaigns have the added task of educating patients on the disease itself. Called nonbranded DTC advertising, it was what Vanda Pharmaceuticals Inc. undertook in the years leading up to eventual approval of Hetlioz (tasimelteon), a selective melatonin receptor agonist, for non-24-hour wake-sleep disorder. Vanda initiated what CEO Mihael Polymeropoulos at the time called a "very broad awareness campaign" to describe the chronic, circadian rhythm disorder that typically affects the blind, though it still remains to be seen whether those efforts will translate into sales of Hetlioz. (See BioWorld Today, Feb. 3, 2014.)

Also challenged with explaining a relatively newly recognized disorder is Shire plc, which is promoting Vyvanse (lisdexamfetamine dimesylate) in the recently approved indication of binge eating disorder, though the Dublin-based pharma has struggled with media backlash, highlighting another risk of DTC advertising: public criticism citing increased costs, alleging overuse of medications and accusing drug companies of disease-mongering.

"Some people look at DTC as an annoyance or an inappropriate thing to do," McCourt said. "We look at it differently. We look at patients who are suffering who would never have gotten the relief we're providing them."

BUILD FDA RELATIONSHIP EARLY

Ironwood is in somewhat of a unique position in that Linzess was able to enter a market through a door previously cracked by Zelnorm. But, with Zelnorm out of the picture, Ironwood still gets to enjoy having a drug with first-mover advantage.

"Can I grow and shape [the market] and capture a disproportionate share at the same time?" McCourt said. "That's where we are right now."

At the first of this month, Ironwood launched a new DTC campaign. While the inaugural effort focused on the functional part of the disorder – the symptoms and the solution – McCourt said the new ads will be more emotional, focusing on the patients themselves and, hopefully, "broadening the value proposition.

"We've only scratched the surface," he said. "We've treated about 500,000 of that 10 million [IBS-C patients unsatisfied with existing treatments], but there are another 15 million who are not seeking care that we want to bring into the equation. So certainly there's a lot of work to do to see how better to understand these patients.

"This is a very dynamic learning experience for all of us," he added.

Part of that is the changing landscape of DTC marketing. Previously, DTC "was all about TV; not it's fully integrated: online, print, point of care, the pharmacies and other places patients go to for help," he said. Plus, there's social media. "We have to ask, 'How do we evolve that space as well?'"

One absolute McCourt advises is to start a conversation with the FDA as early as possible.

"From day one, when we started negotiating the product label, we had a pretty good idea of what we wanted on that label to differentiate [the product] and educate the physician and also to educate the consumer," he said. "We worked relentlessly with the FDA to make sure key components were in the product label up front."

Getting that FDA input often will delay the timing, McCourt acknowledged. "But it's the right thing to do." With a well-aligned label, Ironwood did not experience much "pushback" from the agency's Office of Prescription Drugs Promotion and, when the company and its partners went back to the agency with its proposal for the recently launched campaign, the FDA "had almost no comment because we had been in constant communication.

"You really have to treat the FDA as your partner."

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