Friday, 14 July 2017

#ClinicSpeak & #PoliticalSpeak: indication-based pricing is one-way to get ocrelizumab to PPMSers

Before we short-changed PPMSers can we think for creative solutions to the pricing of ocrelizumab? # ClinicSpeak #PoliticalSpeak

I am rather disappointed with the survey response I have had in relation to the results of the ocrelizumab PPMS study and whether or not the results are clinically meaningful. I am deeply concerned that pwPPMS in the UK will not have access to ocrelizumab because it will be priced to treat relapsing-forms of MS and this will make it too expensive to pass cost-effectiveness thresholds for PPMS. In PPMS the cost will be compared to best supportive care and it is highly likely that NICE will say ocrelizumab is too expensive. This means those who can afford to pay for ocrelizumab privately will do say. Life sucks if you poor you won't be able to access ocrelizumab. 

I have argued many times for differential pricing of ocrelizumab, i.e. a lower price for treating PPMS will make it cost-effective. Is the NHS and Roche ready for differential pricing? There is an interesting perspective piece in this week's NEJM covering indication-based pricing, which is another term for differential pricing. It is a very good read and makes a strong argument for differential pricing. 

If you have not done so already can you please complete the survey below? I plan to publish it online and send it the EMA and NICE at the appropriate time.

Thank you.

Effects of Uniform Pricing versus Indication-Based Pricing. In scenario 1, the value of the treatment is relatively retained across indications; in scenario 2, the value is low for indication C, which affects a relatively large population.

Chandra & Garthwaite. The Economics of Indication-Based Drug Pricing. N Engl J Med 2017; 377:103-106.


...... Pharmaceutical treatments and medical devices often have varying effectiveness depending on the indication for which they’re used: in oncology, for instance, response to a treatment varies with the type of tumor and stage of disease. The advent and proliferation of precision medicine in which biomarkers — whether genomic, proteomic, or structural — identify patients likely to receive greater treatment benefits only increase the range of variability in the effectiveness of the same product.

...... Yet manufacturers traditionally charge the same price for all indications. Recently, there have been calls for “indication-based” pricing systems, in which manufacturers are paid more when treatments are used for indications for which they have higher value (“high-value indications”) and less for indications for which they confer less benefit (“low-value indications”). Supporters hope that such a system will reduce prices for low-value indications but that prices for high-value indications will not increase. This expectation arises from a belief that manufacturers currently set uniform prices according to the value generated for high-benefit indications and somehow get patients who receive lower value to pay the same price.

CoI: multiple


  1. NICE pricing is already driven by the QALY model...

    The onus is on Roche to prove the QALY factor for PPMS.

    Tony F


  2. If all MS is MS, ie we all have lesions of some sort and atrophy rates of varying speed, then why can't we get the most appropriate drug? Conversely, why can't we all be diagnosed with RRMS if the biology is the same?

  3. Though I don't live in the UK, I did try answering your survey. However, the yes/no nature of some of the answers leaves no room for the fact that Ocrevus most likely will only be beneficial to a fraction of the PPMS population.

    In a previous post, Dr. G has mentioned that given the patient population of the Ocrevus PPMS trials, proper prescribing guidelines would likely exclude 70% of the PPMS population. So a question such as "do you agree that the ocrelizumab trial results show that PPMS is modifiable?" should include as one of the possible answers "yes, but only for a subset of the PPMS population".

    Please correct me if I'm wrong, but is there any real reason to believe that Ocrevus will benefit patients who fall outside of the responder group as identified by the old Rituxan trials? That is, patients under 50 years of age, who have had the disease less than 15 years, and are still ambulatory? Also, isn't it likely that the drug will prove much more efficacious in patients with enhancing lesions? Of course, this subset breakdown was not provided by Roche, though I'm sure the dataset must exist somewhere.

    If only be Ocrevus PPMS trials were compelling enough to inspire a resounding "yes" to the first two questions on your survey. Unfortunately, I don't see how a "yes" is warranted, unless accompanied by some caveats.

    The recent study of lipoic acid on progressive MSers showed that, when brain atrophy is used as an outcome measure, this natural supplement far exceeds Ocrevus in terms of efficacy. The lipoic acid trials were relatively early stage, but still…

    My fear about Ocrevus is that it's approval for PPMS by the FDA will hinder research into compounds/treatments that might actually be of much greater benefit to people with PPMS. Much as we've seen with RRMS, the success of the DMT's has certainly shifted the focus away from finding the root cause of the disease and onto looking for newer and better ways to suppress the immune system, an approach that will never, ever, lead to a cure.

    And then, of course, there's that bothersome cancer signal (more than one in 50 patients developed a malignancy during the two-year Ocrevus PPMS trial). Yes, maybe an outlier, but then again, maybe not.

    Lots of questions regarding this drug, and hopefully all will be answered in a positive manner as time goes on. But I find it hard to see how anybody can issue a full throated endorsement of this drug for PPMS given the modest amount of benefit versus possible risk, especially when talking about the PPMS population as a whole. For those patients who fall into the likely responder group, there's a much stronger argument to be made in favor of the drug. For others, though, I fear the drug may offer false hope.

    1. MS is looking likely to be a primary autoimmune disease with secondary neurodegeneration though.

  4. Dr. G, May 15, 2017: "if you are going to select patients for treatment I suggest you use the the three inclusion criteria above as your guide. I predict that these will probably exclude 70% of a typical PPMS clinic population."

    1. Possibly. With therapeutic lag I suspect people with PPMS outside the 2-3 year responder group will respond later. I have encouraging Roche to do a trial in people with more advanced MS, i.e. similar to our CHARIOT-MS, population using the 9-HPT as the primary outcome measure. I am sure that even wheelchair users will respond as their upper limbs will have reserve and report out sooner.

      The negative results in progressive MS trials is mainly due to poor trial design and not biological reasons. This is why we are trying to get the larger community behind our #ThinkHand campaign.


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