Differentiating novelty in the complex oncology market

Maie Gall

Matems Consulting Ltd.

As another American Society of Clinical Oncology (ASCO) meeting closes with an incredible amount of new compounds, new products, new indications and new combinations, one is left with the question: How can a prescriber choose? What, how and when can the industry make recommendations on using which compound or product?

In a market blessed with innovation as the haematology/oncology market has been historically and no doubt will be for many years to come, the choices are overwhelming for prescribers as well as other stakeholders. Innovation is not only offering new options to larger more established tumour types such as colorectal cancer but also for smaller rarer ones such as glioblastoma. In addition to efficacy in a certain tumour type the prescribers have to also decide on a suitable mode of action (MoA), and with every new year more specifically targeted approaches emerge bringing with them multiple products.

From a patient perspective it is great to have so many options at a time when they need as much hope as possible to get them through such a difficult time in their lives. However, from a prescriber perspective, keeping track of all these developments is impossible, making their dependency on easy to understand, clearly directed materials that are taking their interests and needs into account, extremely important. The industry has certainly complied with some innovative new approaches around such materials such as web based prescribing tools. But if all these materials are just created with classical differentiation variables such as efficacy and safety/tolerability parameters, are they fulfilling the prescribers’ needs, or are these two parameters just the entry ticket to even speak to him/her about a haematological/oncological drug?

"From a patient perspective it is great to have so many options at a time when they need as much hope as possible to get them through such a difficult time in their lives."

Multiple compounds have used the approach of differentiating on MoA. This is, of course, a very valid parameter as targeted agents only demonstrate efficacy based on the way they work. Clearly the mechanism also determines the safety/ tolerability profile that is to be expected and, as a result, which other variables need to be managed. However, with so many novel MoAs available, once you have explained this at pre-launch to a prescriber will he or she prescribe the product based on its MoA and resulting efficacy? Will that be the deciding factor in their minds versus all the other available targeted modes of action?

Order of entry in an indication or treatment line has also been also used as a differentiating variable. The fact that you are first to market with a targeted agent does give you leverage. If you are the first versus an old established standard of care that is more than 15 or 20 years old in that indication, this it is a different story. However, if you are the newest targeted agent in an indication that beforehand had other targeted agents with other MoA, is this still a good differentiator? Will it register in the minds of a prescriber as something that must be used or will he or she, understandably, compare it to the other targeted agents that are available and try to niche each MoA within some sub-segment of their eligible patient population.

Another interesting approach when assessing new agents has been to base it on possible combinability with established standard of care regimens. Basically the concept is to just put it on top of your already tried and true regimens. This method is very often used in haematology such as combining rituximub (Rituxan/MabThera) with the CHOP (cyclophosphamide, doxorubicin, vincristine and prednisone) regimen in non-Hodgkin’s lymphoma (NHL). Likewise, in solid tumours one can think of bevacizumab (Avastin) in colorectal cancer being combined with the FOLFOX (fluorouracil and oxaliplatin) or FOLFIRI (fluorouracil and irinotecan) regimens. This is an interesting approach as it is, technically speaking, not really a differentiating strategy but more just adding a benefit on top of what is there so the prescriber does not have to decide between options. The one exception being that both these examples include one of the first targeted agents for these indications. Subsequently, many other targeted agents came out as add-ons to established regimens and then the differentiating began.

"...how you differentiate is important, but the question of when you should start marketing your differentiation is also critical."

So how you differentiate is important, but the question of when you should start marketing your differentiation is also critical. Historically “pre-marketing” began at some point towards the end of phase III if not in registration. Clearly, information is released before this point on the compound’s “value” as a treatment option but tends not to be really differentiated. The concern has always been to not risk saying anything until the late-stage clinical trial results are out. Until that point you do not know if you have any significant efficacy or exactly what your safety profile looks like. As a result many companies wait until that point is reached and then start their differentiation. But with so many approaches in the treatment of these indications, is one year to 18 months prior to launch enough to establish a product in the minds of a prescriber when there are so many products coming out at the same time? Is the way that the industry currently does earlier pre-marketing efforts getting the “prescribing” attention of a stakeholder?

Critically, are there other ways to differentiate that may be more effective in these very busy disease areas? Is there an earlier time point where we need to start thinking about differentiating our compounds and, if so, what is the best way to do this?

Perhaps instead of thinking of how to differentiate compared to other products/MoAs, we should also think about it from the perspective of the prescriber? One could think of the fact that for a prescriber a new approach, novel MoA or a new combination are “just” options among his or her armaments of treatment options. This means that as fascinated as he or she is with the newest innovation, in order to get the prescription, the industry needs to answer three main questions:

1. “So what” does this mean for me and my patients?

2. If I choose this new approach it is “versus what” else that I have in my armaments?

3. Finally, what is the “cost benefit” of such a new approach?

The cost benefit is not solely about price as we need to remember that cost also equals safety/ tolerability concerns and benefit equals efficacy. Additionally, the reality is that their choice will impact their other options with other patients, with budgets and future possibilities of treatment for this same patient depending on the country.

Taking all these variables into account, it may seem that the only real variable for differentiation in the current and future haematology/ oncology market would be “clinical utility”. This basically means that for the prescriber it is not so much about how a product is working as to how much does he or she gain for the patient in efficacy and at what “price”. The industry needs to provide marketing materials, events and tools around the approach of clinical utility from the perspective of the prescriber. Many believe that by describing the level of efficacy they are doing exactly that but one could argue that the level of efficacy is only of interest if it is put in the context of all other options that currently exist for the same patient from the prescribers’ perspective. This is not just competitive positioning as it is taking all options that are currently available into account. So in some incidences the comparator is a very established 20 year old treatment, regimen or technology. Furthermore, very often the industry describes the safety profile thinking that the prescriber can calculate what this means in terms of possible impact on his patient. Intellectually of course they can, however tolerability is not the same as safety and the issues that the prescriber has are more on how to “manage” the patient than if the drug has an “acceptable safety profile”.

"...one could argue that the level of efficacy is only of interest if it is put in the context of all other options that currently exist for the same patient..."

Lastly, as I alluded to earlier the timing of such activities is also very critical. With so many innovations being thrown at the prescribers today, the traditional thought that “pre-marketing” starts at registration or at the end of phase III trials may not be enough to get the prescribers’ attention. The bombardment that is currently happening to them is so high that the industry needs to consider using time in a very different way.

I would suggest that here the right answer is a combination of the various techniques at the various stages of development. However, this comes with a caveat that it is always very much dependent on the type of compound, the indication, the competition and so forth to determine the optimal differentiation matrix of variables and suitable timelines. Ideally the industry would start its differentiation process as early as phase II with a more specific, tailor made approach to each tumour, each type of prescriber and each opportunity for share of voice. Prescribers are, after all, an extremely interested audience but need information that is tailor made to their time and needs, which the industry needs to communicate at the level of use rather than at the level of novelty.

Novelty is, by definition, temporary and may be of less importance at the following year’s ASCO meeting.

About the author:

Maie Gall is a commercial strategy expert at Matems Consulting, a specialized consulting company focusing on haematology, oncology, rheumatology and diabetes. With offices in the US, Europe and the Middle East, they offer a broad service offering for these indications from Phase I to post patent expiry strategy as well as tactical implementation. Combined, they have more than 75 years of industry experience at large pharmaceutical companies in local, regional and global functions. For more information including the CVs of the partners, please visit their website at www.matems-consult.com or contact Maie at maiegall@matems-consult.com, tel +41 79 788 6523.

Are new methods needed to differentiate novel oncology assets?