Orphan Diseases: Rare Rivalry
With two drugs for one ultra-orphan disease—Kynamro and Juxtapid—getting FDA's nod a month apart, intense competition is in the cards. Tanya Lewis looks at their commercial launches
On January 29, 2013, the FDA gave its thumbs-up to Kynamro (mipomersen), an injectable therapy for homozygous familial hypercholesterolemia (HoFH), a rare life-threatening genetic disorder characterized by extremely high cholesterol levels. Discovered by Isis Pharmaceuticals, Kynamro is being marketed by Sanofi's Genzyme unit, which has a long history in developing and marketing rare-disease therapies.
It came on the heels of the December 21, 2012, approval of Aegerion Pharmaceutical's HoFH pill, Juxtapid (lomitapide)—the biotech's first commercial product. (While Aegerion is a relative newcomer to the orphan space, its CEO Marc Beer is not. See sidebar beow.)
Both drugs were granted orphan status, as the disease affects about 3,000 people in the US. Prior to these approvals, treatment options included statins, cholesterol absorption inhibitors, bile acid sequestrants, and niacin, as well as LDL apheresis, a two- to four-hour procedure conducted every two or three weeks in which a machine removes LDL from blood plasma.
The existence of competition is no surprise, says Mike McCann, VP, global strategy marketing in Genzyme's cardiovascular division. “We knew about Juxtapid coming out,” he says. And “LDL apheresis was available when these products were going through [development] and is still an available option for some patients today.”
Though he acknowledges that this is probably one of the few times in which two products for the same ultra-orphan disease have come to market at the same time, McCann downplays their rivalry.
“It doesn't really change what we do,” he says. “We'll contact physicians and talk about the benefits [of] Kynamro. From an education standpoint, people have to be aware of other options, but we're still focused on our product and the value it brings to patients.” In fact, he adds, “Having other companies talking about this rare disease is good because there's low awareness.”
Nevertheless, intense competition between the new treatments is playing out. For one, Genzyme priced Kynamro at $176,000 per patient per year vs. the $295,000 per patient per year Aegerion charges for Juxtapid. McCann insists that several factors went into pricing its medicine (“We used cost of LDL apheresis as a benchmark,” he says), but Juxtapid's cost was not one of them.
There are safety concerns around the new drugs. Both carry Boxed Warnings—the most serious kind—on the risk of liver toxicity, and each is launching with a REMS program.
But either one offers HoFH patients and their physicians a treatment option that may help to significantly reduce LDL cholesterol levels. Among clinical trial participants taking Kynamro, LDL-C dropped 113 points, or 25%, on average across four Phase III studies, with no change to diet or other therapies.
By comparison, Aegerion says HoFH patients taking Juxtapid in one Phase III trial saw a 40% drop in LDL-C, although that was after the med was added to subjects' existing lipid-lowering therapy.
To make Kynamro's case, a team has been calling on payers for at least a year. “They have relationships, so they've been able to talk about the disease and participate in advisory boards to understand how the payers feel about the product,” McCann says.
How will Kynamro's price and delivery differences—it's a once-weekly shot, while Juxtapid is a daily pill—play out in treatment and reimbursement decisions? Physicians should choose Kynamro based on its benefits vs. cost, while payers should support access to the appropriate therapy for individual patients, McCann maintains, adding that Genzyme is framing the injection as a plus.
“This is a chronic, potentially lifelong therapy,” McCann explains. “Patients are already taking as many as 17 pills a day. The fact that you can get a 113- point LDL-C reduction in a single weekly injection is something some patients should see as fitting into their lives. There's a level of commitment required for a chronic disease, and we see weekly self-administration as an advantage.”
McCann won't disclose Kynamro's marketing budget or sales force size, except to say that given Genzyme's experience, the company feels the size of the force is “commercially appropriate,” and the sales team brings skill in orphan products. Lipid clinics and lipid specialists are being targeted.
Among other elements of the marketing plan, Kynamro Cornerstone, an opt-in patient support program in which each patient is assigned a dedicated RN case manager, launched January 29. Offerings include reimbursement support, financial assistance for qualifying patients, in-person injection training, and disease and product education for HCPs, patients and caregivers.
The access program is among the most critical aspects of Kynamro's marketing, says Alicia Secor, Genzyme VP and GM of endocrinology and cardiovascular. Since the fall of 2010, Rosetta has been creative AOR for Kynamro, with Siren Interactive serving as digital AOR since March 2011.
That same year saw the launch of FHJourneys.com, a website with numerous educational and support resources including an animated video explaining the disease and patient stories. It also maintains an FHJourneys YouTube channel housing additional videos.
n addition, the company partners with organizations such as the National Lipid Association (NLA) and Preventive Cardiovascular Nurses Association (PCNA) on educational materials, and Genzyme medical affairs employees and medical science liaisons started engaging thought leaders about 14 months prior to approval.
While attention is now focused on bringing these two HoFH treatments to market, one could say that competition between Kynamro and Juxtapid started during R&D. Recruiting for clinical trials is notoriously difficult in the orphan space, and the scope of subjects is limited further when multiple companies are vying to develop products for the same indication.
McCann says the two firms' studies had some overlap but that Genzyme didn't face added difficulty in recruitment. That's because Aegerion sought a different type of patient—Juxtapid's placebo-controlled trials allowed for patients receiving LDL apheresis, whereas the Kynamro trial did not include patients on the older treatment.
McCann says Genzyme reached out to physicians knowledgeable in the lipid space and drew from treatment sites worldwide, including some in areas such as South Africa, Lebanese communities and French Canadian communities.
Genzyme has stewarded many an ultra-orphan drug launch, but McCann points out a key difference with this one: HoFH can be diagnosed either clinically or through a genetic test.
"Testing for LDL is pretty common, and LDL is one indicator of FH and HoFH,” he says. “So the fact that we have the LDL test, which one might even call a routine test, is different.” That's important, he says, as “Hyperlipidemia is a large market…and patients with this disease can sometimes get lost or misdiagnosed as simply having high cholesterol as opposed to having the genetic disease.”
Vets meet on orphan-drug playing field
Before taking the reins at Aegerion Pharmaceuticals, CEO Marc Beer worked at Genzyme, the rare-diseases drug maker now owned by Sanofi, rising to VP of global marketing. Below, he weighs in on the commercial launch of once-daily pill Juxtapid, which received an FDA green light a month before Genzyme's once-a-week shot Kynamro. Both drugs were approved to treat homozygous familial hypercholesterolemia (HoFH), an ultra-rare cholesterol disorder.
How did you prime the market prior to Juxtapid's approval?
MB: Our focus was to find the patients by meeting with physicians. We built our global patient tracker to approximately 1,500 potential patients in advance of launch.
Did the potential approval of Kynamro impact your pricing ($295,000 per patient per year)?
MB: Aegerion expected and planned for the FDA approval of Kynamro, but we did not factor it into our pricing decision. We do not expect physicians will prescribe medicine to treat HoFH patients based on cost.
Is the competition from Kynamro impacting your marketing plan?
MB: Having more FDA-approved treatment options to treat HoFH is good news. However, doctors and patients will appreciate the clinical profile of Juxtapid as an oral treatment that has been shown to reduce LDL-C levels with a safety profile that we believe is manageable with proper monitoring as required in the REMS. We don't view it as a race against competition, but rather a race against this terrible disease.
How big is your sales force?
MB: 25 sales reps are targeting academic lipid specialists, community-based specialty lipidologists, and cardiologists.
Tell us about the marketing team.
MB: Juxtapid is primarily handled in-house, though some project work has been contracted to unnamed agencies. There are no plans at this time to issue an RFP, according to a spokesperson.
What's the main marketing message?
MB: The patient is waiting…There's still much to be done to achieve our commitment of delivering this important therapy to HoFH patients.