Pharma Strategy Blog

Commentary on Pharma & Biotech Oncology / Hematology New Product Development

Posts tagged ‘adcetris’

“The problem at the moment is that it takes $1bn [£600m] to get a drug to market and 15 years or more. That is the justification for the pharmaceutical industry charging high prices.

If on the other hand by the time you get to phase 2 you know exactly which patients it is going to work on, you only put those patients through and instead of 10% you get an 80% response rate.

You get a licence on the basis of the data and don’t have to go to phase 3 (a trial involving thousands of people). That saves vast sums of money and years of development. What that does to the business model is it means you can justify charging lower prices because it cost a lot less in the first place.

If we get this right, it changes the entire dynamics of the business model of the pharmaceutical industry.”

Source Harpal Kumar, the chief executive of Cancer Research UK (CRUK) via The Guardian

A UK friend kindly sent me this article today and provocatively asked me what I thought. Hmmm, a very interesting, meaty and relevant topic indeed.  Here goes…

Will this change the way we do business in cancer research?

The theory behind this statement by CRUK is that if we develop more targeted drugs to fewer patients and generate higher response rates e.g. 70-80% in a specific biologic subset, instead of say, 10% in a broader population, then the costs of development will come down and thus the treatment cost of the disease will ultimately lower.

Not so fast!

The reality might actually be different, and here’s why:

  1. For this to happen you need more translational research, biomarkers and companion diagnostics.
  2. The cost of researching and developing the targets is quite high.
  3. While clinical development costs might be lower with fewer large scale trials, the costs of iterative phase II trials will go up and the available pool of patients for commercialization is now much lower e.g. 5% of patients with the ALK translocation in lung cancer not 100% of all available relapsed patients.
  4. In order to maintain revenues, it is basic economics 101 that smaller patient niches will equal higher costs.

If you are not convinced of the last point, take a look at the costs of treating rare diseases or small subsets of patients.

Some good examples exist in the hematology space include:

  1. Alexion’s Soliris (eculizumab),which is approved for the treatment of patients with paroxysmal nocturnal hemoglobinuria (PNH). This is a rare hematologic disorder that affects approx. 8,000 to 10,000 people in North America and Europe. The cost is something like $400K per annum.
  2. Genzyme’s Fabrazyme (agalsidase beta) for the treatment of Fabry Disease, another rare hematologic condition, this time an inherited metabolic defect that affects 1 in every 40-50,000 people in the US. Fabrazyme lowers the amount of a substance called globotriaosylceramide (GL-3), which builds up in cells lining the blood vessels of the kidney and certain other cells. It’s very effective, but certainly not inexpensive at around $160K per annum.

What is the likely impact of the changing research paradigm?

Both of the above patient pool sizes are not out of the realm of reality for a comparison with oncology.

In the old model, clinical trials tended to involve more allcomer trials, i.e. patients with a particular tumor type (e.g. non-small cell lung cancer), stage of disease (metastatic) and line of therapy (frontline, relapsed or refractory).

In the new world order, things are changing in clinical trials already:

  1. Roche’s Zelboraf (vemurafenib) was recently approved in metastatic melanoma in patients with the BRAF V600E mutation, reducing the available pool who might respond by 50%. It was launched last week with a price tag of around $56.4K for an average of 6 months treatment.
  2. Crizotinib (Xalkori) is being evaluated in patients with NSCLC who have the ALK translocation and have failed prior therapy. That’s a tiny subset of patients. Patients with this aberration make up maybe 4-7% of the total NSCLC pool. Imagine how small the target population will be for other ALK inhibitors in crizotinib refractory disease?!
  3. The cost of funding and finding biomarkers that predict response is a huge undertaking.  Genentech have no doubt spent many millions looking for a predictive biomarker for Avastin, so far to little avail.

Of course, there are plenty of other exciting targets with small subsets being evaluated in the clinic, but there are several factors to consider:

  1. Small subsets = fewer patients = higher cost.
  2. Will combination strategies be affected by the cumulative costs that will inevitably result? e.g. Yervoy + Zelboraf in metastatic melanoma potential treatment cost = $170-180K if the studies are successful in showing that survival is improved.
  3. Since Dendreon’s Provenge ($93K) was recently given the green light by the CMS, the costs of new targeted entrants is creeping up over the $100K watershed marknot down, viz Yervoy ($120K) and Adcetris (~108K), for example.

In conclusion…

I admire the chutzpah of CRUK, but disagree with some of their conclusions, which I think are rather naive.

Today, I will go on record here and declare that I believe specialised treatment based on the underlying biology will ultimately cost more, not less, in the long run in terms of research and development, diagnostics/biomarkers and treatment costs of ever smaller subsets.

However, I have no doubt we will ultimately see better results clinically with this more scientific approach but this will come at a cost.  While that’s great news for patients and caregivers, it is not so great for the payers, Government or investors, because higher risks and R&D costs will inevitably equate to more failures and this drives higher costs in a spiral fashion.  Ultimately, those costs will trickle down to all of us in the form of higher co-pays and more expensive medical plans to cover the payers margins.  Success has to be paid for somewhere down the line.

And the constant refrain from everyone in Pharma of “let’s do more with less” will increase.

It’s a vicious cycle of unsustainability, with no end in sight.

9 Comments

This morning, Seattle Genetics announced that the expected fast track approval from the FDA has been forthcoming for brentuximab vedotin (Adcetris) following the recent unanimous ODAC voting in both refractory Hodgkin Lymphoma (HL) and Anaplastic Large Cell Lymphoma (ALCL).  Clearly, the company and the agency have come to agreement on the confirmatory trials as part of the condition of accelerated review.  The final prescribing information (PI) can be found on the Adcetris website.

For those of you looking for more information on Adcetris, please check out the related posts section below for previous reports on this novel ADC therapy.

I missed the conference call this morning announcing the pricing details, but Luke Timmerman from Xconomy had a nice summary:

“The company set the price at $13,500 per dose, given intravenously every three weeks. If patients get eight infusions on average, consistent with clinical trial experience, then it will cost $108,000 per patient.”

Based on the data from the clinical trials, most patients will probably need 7-9 cycles, so this would make the overall course in the $94,500 – $121,500 per treatment range, with $108K being the average based on 8 cycles.  The overall treatment cost will therefore typically be less than the $120K cost of treatment for BMS’s ipilimumab (Yervoy) in metastatic melanoma.

Ever since Dendreon announced the $93K course of treatment for Provenge in asymptomatic castrate resistant prostate cancer (CRPC), there has been a noticeable trend upwards in the cost of treating advanced cancers.  We probably spend more treating the last 6 months of a cancer patients life than any of the other stages combined with incremental rather than dramatic improvements.  In the long run, this is likely to be unsustainable, but for now companies will continue to charge what they think the market will bear.

The good news is that Adcetris offers excellent clinical proof of concept for antibody drug conjugate (ADC) technology and has the distinction of being the first such agent approved, beating Roche’s T-DM1 to market, which has been filed with the FDA for the treatment of HER-2 breast cancer.

In the meantime, we also have several other novel therapies awaiting final review by the FDA.  Aside from T-DM1, Pfizer filed crizotinib for ALK-positive lung cancer and now has a brand name, Xalkori, which I thought sounded rather Vulcan :).  Should these two agents also receive FDA approval in the very near future, 2011 will likely be a bumper year for new cancer drug approvals.

 

2 Comments

This weekend heralded the sixteenth annual meeting of the European Hematology Association (EHA) conference at the ExCel centre in the London Docklands. Completing back to back ASCO and EHA conferences across two continents will test any delegates stamina!

Like ASCO, this year was a relatively quiet one at EHA, with most of the data already known or presented elsewhere.   There were some gems in the program though.

In the latest video highlights I discuss three things that caught my attention:

  1. Is high dose cytarabine (ara-C) really necessary in AML?
  2. Brentuximab vedotin in anaplastic large cell lymphomas (ALCL)
  3. Adherence with chronic TKI therapy in CML

We have previously covered the excellent data for brentuximab vedotin (Adcetris) in Hodgkin Lymphoma, but the new data presented in ALCL in the poster session was, in ways, even more dramatic as you can see from the before and after pictures included.

You can see from the video, shot on location, that the damp windy weather and rundown surroundings created a rather industrial ambience – not quite the image many may have of the Docklands and Canary Wharf, which is a couple of stops earlier on the Docklands Light Railway (DLR).

Of course, there are unplanned escapades, such as nearly missing the 8am session on Sunday morning after the Jubilee line didn’t begin until 7.20am (first train at 7.35am), then the DLR had a “system failure” at Canning Town. A quick dash down to the adjacent bus station, a frantic climb over a fence in glad rags and a rare taxi was thankfully secured for the mad dash to the ExCel centre!

Still, there is something rather edgy about hosting convention centres in marginal areas in the middle of nowhere-land, quite a trek on the Tube and DLR from the Central London:

All in all, I enjoyed the meeting in my hometown and the more relaxed academic atmosphere after the frenetic pace of ASCO, but by the end of ten days on the road it was nice to return home. It’s not all work and no play though, as you can see from this post about some of the pomp and circumstance that inevitably goes with being in London.

{UPDATE:  The day after this posted, Seattle Genetics announced they have an ODAC scheduled for July 14th.   The PDUFA date is August 30th, so with any luck, we may see this drug approved by the FDA sooner rather than later – great news for patients in the US!}

Quite a few questions have hit my inbox recently from people wanting to know more about Antibody Drug Conjugates (ADCs) and how they work.

They basically consist of three things:

  1. Monoclonal antibody
  2. Linker
  3. Cytotoxic agent

Antibody Drug Conjugate (ADC)

Source: Roche

The goal is to create a new molecule that essentially is greater than the sum of its parts by making it more targeted, like a guided missile against the cancer cells.

With normal monoclonal antibodies, they bind to atarget antigen that is a tumor-specific antigen on the surface of a tumour cell. With an ADC, the monoclonal antibody part of the molecule still latches onto the target antigen in the same way, but in this case it now has a powerful cytotoxic attached to potentiate the effect.

As Emeril would say, “Bam!”

You can see a video of how the ADC technology works HERE.

Unfortunately, the site only allows you to watch it there or download the video; it’s not easily sharable with others, short of emailing it.  Sadly, I couldn’t embed it here on the blog post for easy consumption either.

A nicer way would have been to put the educational videos on a company YouTube channel and allow it to be shared through social media via Facebook, Twitter etc. Imagine clicking on a link in Twitter and being taken to YouTube on your iPad, iPhone or Android smartphone?  Or watching an embedded video on someone’s blog post?

That’s a much more fun and immediate way to communicate ideas and technology from a medical or scientific learning perspective than a old fashioned static website.

It is good to see Pharma and Biotech companies active on social media, but they have a long way to go yet in terms of how they can help improve learning about the science behind new cancer research and development in an integrated way that helps the end users, ie the scientists, healthcare professionals, patients in clinical trials and analysts who might be interested.

We really do need to get away from the old web 1.0 world into the 21st century of sharing ideas, tools and medical or scientific information using social media in the web 2.0 era.

That said, there are some advanced ADC’s in clinical development at the moment.  The three leading compounds I’ve come across so far are:

  • Brentuximab vedotin (Seattle Genetics) in Hodgkin Lymphoma (HL) and systemic anaplastic large cell lymphoma (ALCL) targets CD30 and now has a brand name, Adcetris.
  • T-DM1 (Roche/Genentech) in HER2+ breast cancer
  • SGN-75 (Seattle Genetics) in RCC and NHL

Overall though, Roche/Genentech probably have the largest active research in this area, with a large portfolio of agents in development across a multitude of different tumour types.  You can check out this full ADC pipeline here.

Seattle Genetics have a couple of abstracts on their ADCs at ASCO this year and Roche have an abstract on the phase III EMILIA trial comparing T-DM1 with lapatinib plus capecitabine in metastatic breast cancer, all on Monday 6th that I hope to check out, that is if the sessions don’t clash!

14 Comments
error: Content is protected !!