Cinryze Launch Plans Bear Hallmarks Of Successful Orphan Strategies

ViroPharma/Lev scored a regulatory success with FDA's approval of Cinryze (C1 esterase inhibitor) for prophylaxis of hereditary angioedema. Now the firm needs to concentrate on turning that into a commercial success - and with the launch plans recently laid out, the firm seems poised to do that.

ViroPharma, which completed its acquisition of Cinryze developer Lev Oct. 21, reviewed its promotional plans for the orphan drug earlier this month. The launch strategy contains many of the elements that previous orphan drug marketers have developed over the past few years, as firms like Genzyme and Shire have transformed the orphan field from a peripheral, unattractive genre into a viable business strategy.

With elements like disease-awareness efforts, alliances with advocacy groups and a patient access program, the launch of Cinryze seems to represent the state of the art for orphan drug marketing.

Cinryze is the first U.S. approval for HAE, an orphan condition that manifests through inflammation of the larynx, face, abdomen and extremities. Laryngeal attacks can be fatal. The Hereditary Angioedema Association says there are about 4,600 identified HAE patients in the U.S. - the total including undiagnosed patients is estimated at 10,000.

FDA's Oct. 10 approval of Cinryze was for prevention of HAE attacks. The agency's decision to split the indication into prophylaxis and treatment of acute attacks means the race for the treatment indication (and orphan exclusivity) is still on for the C1 esterase class (¹ (Also see "Cinryze Prophylaxis Approval Leaves Window For HAE Treatment Contenders" - Pink Sheet, 3 Nov, 2008.), p. 17). With other companies advancing therapies that use other mechanisms to target HAE, the market is likely to see some competition in the near-term.

But as the first approval for the orphan condition, the Cinryze marketers face the additional challenge of improving disease recognition, rather than just promoting their therapy.

Lev laid substantial groundwork aimed at increasing physician and patient awareness of HAE. That work started even before Lev submitted the biologic for approval, such as working with clinician groups to set protocols and enroll patients in clinical trials.

Capture The Patients You Know

Recognizing that the clinical trial process also really was establishing a potential patient population for the marketed product, Lev permitted all patients who completed Cinryze trials to remain on treatment through "compassionate use" open-label studies of the drug. ViroPharma now is hoping to transition those patients into the early commercial adopters.

ViroPharma's commercial goals start with getting all HAE patients in need of prophylaxis on therapy (before addressing the treatment market). The initial focus is transferring approximately 200 open-label study participants and the 350 patients who have signed into the Cinryze registry into commercial use of the drug; the firm also is targeting the physicians of the roughly 1,500 patients who elected to use anabolic steroids, despite their side effects, as prophylactic therapy prior to the availability of Cinryze. ViroPharma acknowledges there could be some overlap between those groups.

Reaching Out To Advocacy Groups

In rare conditions, the patient groups usually are the best allies for a company launching a new therapy. "We view our relationship with the HAE association as an essential partnership," ViroPharma COO Daniel Soland said. The two collaborated on a patient registry, which helped identify patients for the clinical trials.

Lev also reached out to the National Organization for Rare Disorders, leveraging its position and insight into the orphan community. The advocacy group often has been an ally for orphan drug sponsors, both with development and marketing.

NORD published and has been disseminating a free booklet, "The Physician's Guide to Hereditary Angioedema," that was funded by Lev. The booklet has reached approximately 73,000 clinicians, and NORD estimates Lev's total costs in financing the guide at $40,000. The booklet, which aids with recognition and diagnosis, is a crucial part of the disease awareness foundation for the Cinryze launch.

Mary Dunkle, NORD's VP for communications, said Lev's work in education and raising awareness about HAE probably improved the likelihood of success for any FDA-approved HAE therapy.

"That just stuck in my mind as forward-thinking and a really good example of a company in the first place reaching out to the patient community and trying to involve us in raising awareness," she said. "It doesn't do any good to bring a product to market if doctors aren't going to recognize the condition."

Of course, that also leaves Lev/ViroPharma with the classic conundrum of disease-awareness campaigns: efforts to establish/grow the market stand to benefit all products, not just their own.

One of 10 such booklets on rare diseases published by NORD, Dunkle says the HAE guide is one of only two funded by a company. Most are funded by patient advocacy groups. The association says it controlled the content, which was reviewed by three experts in the disease as well as NORD's own staff physician.

"The intention was that HAE is a medical condition that gets misdiagnosed or unrecognized frequently," Dunkle said. "We were reaching out to emergency room physicians, people who might be on the front lines in the sense of possibly being able to recognize [HAE] early, and help patients get a diagnosis or get treated more appropriately."

Lev also is among roughly 50 companies on NORD's Corporate Council, described by Dunkle as "a neutral setting where companies can talk about the challenges of bringing a product to market, challenges related to doing research with small patient populations."

Patient Access Program Part Of The Plan

ViroPharma also is using another now-standard commercialization strategy for ultra-orphan therapies, necessitated by the high prices associated with those drugs: a patient assistance program.

Despite the high pricing, ViroPharma pledged that its patient access program - CinryzeSolutions - will ensure that "every patient who needs Cinryze will get it, regardless of their insurance or inability to cover the cost." Cinryze has a per-dose wholesale acquisition cost of $3,900, or an average annual price tag of $358,800 (² (Also see "ViroPharma Sets High Pricing For Cinryze, Unveils Promotional Plan" - Pink Sheet, 6 Nov, 2008.)).

Especially in orphan conditions, patient access programs can serve as support programs that sustain patient utilization. ViroPharma describes CinryzeSolutions as "a personalized access and treatment program for patients with HAE and their health care providers." It will work with patients on reimbursement, either through their insurance or by directing "patients in need toward a resource that can provide co-payment and premium assistance."

ViroPharma anticipates widespread third-party payer adoption of Cinryze, an essential step for a high-cost therapeutic. The firm has contracted with CVS Caremark and CuraScripts as specialty distributors to work out reimbursement details with managed-care organizations.

Soland noted that with other ultra-orphan drugs, it has been relatively easy to get support from payers. That was the case for ViroPharma, he reported. "We went out to managed-care organizations of our open-label patients ... to see their desire to cover the drug," he said. "There was very little push-back, if any, and we expect more than 90 percent of these MCOs will reimburse for the drug as written by the physician."

Small Field, Small Sales Force

ViroPharma believes there is a core group of approximately 200 physicians it needs to target. With such a concentrated group of treating physicians, a small sales team should suffice.

Eighteen of 20 planned sales representatives have been hired, Soland said, with training underway. "Many will be in the field in the coming two weeks, with the initial goals of profiling and helping treating physicians to enroll patients into CinryzeSolutions."

He said the sales reps have extensive experience with specialty products and will focus on roughly 800 doctors, mostly allergists and immunologists. "In addition to the sales force, we have 10 regional medical scientists who were trained in October and are already engaging thought leaders and visiting clinical sites to ... help transition patients from clinical trials."

As the launch progresses, the regional medical scientists' role will shift toward increasing awareness and educating health care providers, working with ER doctors, general practitioners, pediatricians, OB/GYNs and other clinicians to help them recognize HAE attacks and identify undiagnosed patients.

Active promotion of Cinryze starts in December, when ViroPharma expects to begin shipping product into the distribution channel.

- Joseph Haas ([email protected])