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Winning In Ultra-Orphan Drug Markets

A Playbook for Drugs for Rare Diseases

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A new and rarefied breed of pharma marketers are re-inventing marketing itself in their quest to cure the world of ultra-orphan disease, which afflict fewer than 10,000 people in the US market. These “thin” markets are unique because the patients are hard to find and often wrongly diagnosed, lab tests to identify their condition may not exist, the treatment may be a complex combination of new drugs, procedures and devices, and the doctors whose care the patients are under may have no clue as to what they are treating and may see a qualifying case only once every few years. Recruiting for clinical trials is challenging as also is identifying appropriate end points. Drug prices thus end up being high, leading to public outrage and unwanted attention in the press.

Yet, there is a lot to like about the ultra-orphan drug market. The Orphan Drug Act of 1983 (ODA) allowed for 7 years of exclusivity against similar competing drugs and included annual grant funding and tax credits. The unmet need is high – an estimated 30 million Americans suffer from a rare disease and of the 7,000 such diseases identified, 95% have no approved treatment. As patients are few, drug prices of $200-300,000 per year per patient are increasingly the norm. Thus far, payers have accepted the high prices, although there are simmering concerns about the trajectory of costs.  The impact on the lives of the afflicted, who for the most part have no choices, may be nothing short of miraculous. The go-to-market model is compact and clinically precise.

Integrate commercial team earlier than usual

In most bio-pharmaceutical companies, the commercial team takes over a developmental asset only after the completion of the phase II clinical trials. However, for ultra-orphan products it is important to consider patient acquisition and payer acceptance issues from the phase II in-gating itself.  Consequently, the “Launch Tracker” for an ultra-orphan drug is different in timing and scope from that for a conventional drug.

In certain cases, the post launch task of finding patients can be made easier if proper diagnosis and a guidance of care for the disease exists. This means developing partnerships with diagnostic companies for tests and working with public health administrators on instituting policies around mandatory testing. With the advent of pharmacogenomics and personalized medicine, the value of such anticipatory integrated diagnostic strategies has become apparent. Personalized medicine has in effect transformed what would previously have been mainstream drugs into ultra-orpan drugs. Selzentry™ (maraviroc) was a new kind of HIV therapy developed by Pfizer that blocks the CCR5 co-receptor. For maraviroc to succeed in clinical trials, Pfizer had to determine which patients were most likely to carry the R5-tropic strains of HIV. Such a test was developed by Monogram Biosciences. While many other missteps by Pfizer led to a lack of commercial success for the drug, the early integration of a diagnostics strategy was not one of them and on the contrary the key to gaining an accelerated approval from the FDA for the drug.

For one biologic drug, which we worked on, for Stage 4 recurrent Glioblastoma Multiforme, researchers early on made the decision to dose the drug as a single application post surgical resection. The drug went on to fail in its pivotal phase III trial. A subsequent autopsy of the drug by KOLs indicated that the drug might have been more successful if successive dosing procedures were planned, allowing for a wider margin of error in the application itself, which for most neurosurgeons was unfamiliar and challenging.  Additionally, it would have created a superior economic proposition for the drug manufacturer and centers of excellence. Bringing in a commercial and application mindset earlier in the development could have given this promising therapy a better chance at success.

Think one patient at a time

For ultra-orphan drugs, finding patients is like looking for a needle in the haystack.  Consider the case of Krystexxa (pegylated uricase) for treating patients with Chronic Tophaceous Gouty Arthropathy (CTGA). Of the estimated 30,000 untreated patients, only 2,000 may be eligible for treatment in a given year and are spread out across Rheumatologists, Nephrologists, Podiatrists and in some cases primary care physicians. That is well over 20,000 physicians, of whom only one in ten may have an eligible case each year. In other words, it can be 10 years before a given physician presents an eligible case. If you are that average physician, your interest level in learning a lot about a new treatment that could come in handy once in 10 years is low. And if the treatment involves complexity or risks, which Krystexxa does, that interest level just went lower.

A common approach for rare disease drugs is to establish the so called centers of excellence around academic institutions, very large practices and that odd physician that for what ever reason is very interested in these cases. However, establishing these COEs is not enough, you have to actually find and drive patients to them. One of the techniques that we have used for doing that is to build smart, patient referral models that involve using predictive analytics to identify geographically proximate physicians with a disposition to refer their patients to a treatment hub.

Further, the referrals only happen if you can devise a “what’s in it for me?” value proposition for the referrers.  Without that, the sales rep cannot get time of the day with the referring physicians. In the case of Krystexxa, one possible value proposition for nephrologists can be around improving renal outcomes by controlling gout, a thesis posited by a handful of research papers. In other instances, referring physicians are sometimes concerned about losing their patients to COEs. In that case, it helps to carve out a role for the referring physicians in the post treatment monitoring and care of their patient. Failure to build such a role has led to low acceptance of DBM (deep brain stimulation), a treatment for advanced Parkinson’s Disease, by community neurologists. For each drug, the referral value proposition is different and needs to be explicitly developed.

Choose Tv or Not Tv

One of the more intriguing campaigns to go on TV was by Vanda Pharmaceuticals for Hetlioz (tasimelteon), a drug for a rare sleep disorder called “non-24” that afflicts an unknown number of blind people in the US. A $20MM television campaign, targeted at care providers for blind people that themselves cannot see your advertisement, for a drug that netted just $70 million in 2016? If nothing else, this highlights the extent to which ultra-orphan drug marketers must go to think outside of the box to find that needle in a haystack patient. A revenue of $70MM is not high, but the math still works given the high price of the drug at about $148,000 per patient per year. For every 400 patients gained in the year, the drug effectively spends $50,000 per patient in television costs to gain $60 million in annualized revenues. With appropriate care management, that one patient can consume $1.5 million of Hetlioz over the subsequent 10 years making the campaign economical.

If pharma marketers had not figured this out, the lawyers certainly have. In the US there are only 3,000 new cases of mesothelioma per year, many occurring with people that at one time or another were exposed to asbestos. A $30 billion Asbestos Trust Fund was established by 50 companies as part of a settlement, for the treatment of such truly unfortunate patients. Each individual is entitled to about $1.3MM towards their treatment and pain and suffering. The lawyers, who advertise extensively to reach such patients with television and billboard advertisements, charge a contingency fee equivalent to a one third of the proceeds for helping these patients access these funds. Certainly, they have figured out the economics of customer acquisition better than many pharma marketers.

While generally television is thought of as the communication vehicle for drugs with broader audiences, it is increasingly a viable vehicle for reaching high value micro populations of ultra orphan patients, when other means such as sales people canvassing the country prove inadequate. The good news is that for ultra-orphan drugs, you can usually get by with disease awareness versus branded campaigns given the lack of competition during the 7 year exclusionary period. Eliminating the “fair balance” messages thus maximizes the message exposure and focuses the effort on uncovering patients rather than on differentiating the drug.

Look for love in unusual places

For the conventional drugs, the go-to-market models are built around detailing top decile prescribers.  The more they prescribe or the greater their potential to do so, the greater the number of sales calls they receive. However, given the low prevalence of patients, this method often falls short. At some companies, the ultra-orphan sales force may only be 25-30 sales reps that go where and when patients are identified versus having routine call routes.

One of the methods that is emerging to identify patients early is to access diagnostic lab data from companies such as Quest and Lab Corp. As these companies are not in the business of selling data or otherwise provide poorly curated data, it becomes important to work with an experienced intermediary that can provide meaningful information. As an example, using such data, we were able to identify the 3700 FISH, B-Cell Chronic Lymphocytic Leukemia (CLL) Panels that had been tested for patients who were potential candidates for a drug from 34 million total specimens. The data needs to be then mapped to individual practices and physicians whose care the patients may be under, but who may not be aware of the new treatment options.

Another important resource for identifying patients is patient advocacy groups. Patients with orphan diseases are driven by desperation to a search for cure. They often end up taking matters into their own hands and forming their own patient registries. For example, the Friedreich’s Ataxia Research Alliance (FARA) maintains a global registry that currently holds the demographic and clinical information on more than 2,000 patients from across the world, representing many years of painstaking work by organization volunteers. It is critical for ultra-orphan marketers to engage meaningfully with these advocacy organizations early, when the drug is in Phase II trials. In many instances, these organizations may not be as well organized as FARA or in fledgling in certain countries. Thus, it becomes critical for the marketers to get involved in helping those organizations or government health bodies establish working registries.

The advocacy organizations are not only active in maintaing patient registries, but also in funding clinical research and even supporting drug approvals through the FDA. In 2016, the FDA approved a controversial drug, Exondis 51 (eteplirsen) for duchenne’s muscular dystrophy manufactured by Sarepta Therapeutics. Under pressure from a vocal community of parents of children with the disease, many of whom were supported by CureDuchenne, the agency overruled its own medical staffers who had questioned the effectiveness of the drug, which had been tested in only a small clinical trial.

Shape a new world of payer strategies

While payers thus far have not balked at the high prices of orphan drugs given the small number of patients involved, it is safe to say that their own blood pressure is on the rise. With more and more drug manufacturers jumping on to the bandwagon, Evaluate Pharma forecasts orphan drug sales to exceed $200 billion by 2022. That is a number which will get payers’ attention.

Novartis recently introduced Kymriah (tisagenlecleucel), a chimeric antigen receptor T-cell therapy (CAR-T) for refractory and relapsing B-cell precursor acute lymphoblastic leukemia (ALL) at a price of $475,000 after earlier considering price points as high as $800,000, similar to those of analogous stem cell treatments. In a break from tradition, Novartis has adopted an outcomes based pricing model, whereby the company is paid only if the treatment works. This was partly possible due to high response rate of 82.5% for the treatment, which makes the outcomes based effective price $390,000 per patient. Novartis was also under pressure from advocates from Patients for Affordable Drugs, who argued that US taxpayers had funded the development to tune of $200 million prior to Novartis’ involvement. For marketers, this represents a new world in the pricing of ultra orphan drugs.

Build an Ultra-Orphan Go-to-Market Playbook

Ultra-orphan markets require a completely new playbook for go-to-market success that most pharmaceutical marketers are not trained for. In fact, their experience with conventional drugs may be counter-productive and work against them. The new playbook requires a higher level of precision and marketing sensibility. For example, one company that we track decided to partner with a well known advocacy organization but had no in-depth, mutually agreed upon strategy and playbook for what was to be accomplished and an implementation plan. Consequently, well over $5 million was spent in what amounted to an unrestricted grant and nothing tangible was gained. New tools and technology are also permeating the patient care model, enabled by a new world of artificial intelligence and mobile Apps technology, which when thoughtfully designed can be very helpful for these special patients. For the successful few marketers, the economic, professional and societal rewards from building and mastering ultra-orphan drug playbooks are aplenty.


We hope this article helps you prepare better for your next ultra-orphan drug launch. If you would like help with your ultra-orphan drug strategies and playbooks, or simply a PDF copy of this article, please reach out directly to our Managing Director at Cerenti Marketing Group, LLC. is a growth strategy focused consulting firm based out of Chicago. Cerenti has been named one of America’s Best Management Consulting Firms by Forbes Magazine in 2016 and 2017.

Cerenti Marketing Group, LLC.

118 W Kinzie Street, 2nd Floor, Chicago, IL 60654

Office: +1 (855) CERENTi


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