Pharma Strategy Blog

Commentary on Pharma & Biotech Oncology / Hematology New Product Development

Posts tagged ‘Hodgkins Lymphoma’

Seattle Genetics announce fast track approval of Adcetris

By on August 22, 2011

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.

 

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Seattle Genetics brentuximab vedotin accepted for FDA Priority review

By on May 2, 2011

I was delighted to see, amongst all the big news this morning on President Obama and Osama Bin Laden, that there was a little gem for Biotech – Seattle Genetics announced that the FDA have accepted their BLA filings for antibody drug conjugate (ADC), brentuximab vedotin, and awarded Priority status.  The company stated that the Prescription Drug User Fee Act (PDUFA) date is now set for August 30th, based on the Feb 28th filing date.

Two BLA filings were submitted, one for relapsed Hodgkin Lymphoma (HL) and another for relapsed or refractory systemic anaplastic large cell lymphoma (ALCL).  These two hematologic cancers share a commonality, ie CD30, which is the defining marker of the disease and the target for the ADC therapy.

Based on the data we saw at the recent American Society of Hematology meeting in December, the recent NEJM publication, this is very good news indeed for patients.

New treatment options in rare or difficult to treat diseases are always most welcome. With the American Society of Clinical Oncology (ASCO) and European Hematology Association (EHA) meetings both coming up in June, I’m really looking forward to an update of the data and to see how this exciting new concept (antibody drug conjugates) are progressing.

This is an area where I think we will see many more developments in the very near future, with Genentech’s T-DM1 also likely to have data at ASCO in breast cancer.

Tumour associated macrophages and survival in Hodgkins Lymphoma

By on March 15, 2010

While reading my pile of mail on Friday, I realised that an interesting paper on Hodgkins Lymphoma (HL) appeared in the current edition of the New England Journal of Medicine (full reference below).

The basics of the paper are that despite advances in HL, including curative radiation in the early stages if the disease, one third of patients with advanced disease and about 15% of those with early disease have a relapse after treatment. 20% of people still die from the disease.  

The question is why?  

Well, unfortunately, current prognostic models have not been shown to be very accurate and so far, no biomarker has been found to be particularly useful.

The authors set out to use gene-expression profiling obtained from people with HL during diagnostic lymph node biopsy to determine which signatures were correlated with treatment.  They confirmed their findings with an independent cohort of 166 patients using standard immunohistochemical analysis.

What they found was fascinating:

  • A gene signature of of tumour associated macrophages was associated with primary treatment failure.
  • An increased number of CD68 macrophages correlated with likelihood of relapse after autologous stem cell transplantation.
  • The adverse prognostic factor (macrophages) outperformed the current International Prognostic Score for disease-specific survival.
  • The absence of an elevated number of CD68+ cells in patients with limited stage disease defined a sub-group of patients with long-term disease specific survival of 100% with the current therapies.

When I was at school, we learned that macrophages were associated with an immune response to invasion.  According to the NEJM Editorial, by DeVita and Costa, this may not be the case:

"Most of the evidence, however, now links the presence of tumor-associated macrophages with a poor prognosis."

In short, the data shows that increased number of tumour associated macrophages was strongly associated with shortened survival in HL and provides a biomarker for prognosis and risk stratification.  What does this all mean though, for clinical practice?

DeVita and Costa noted that:

"If at the time of diagnosis we could identify patients who are destined to have a poor response to treatment, most patients could be spared a combination of therapies or radiotherapy with its attendant long-term toxic effects."

This is an important observation alone.


For the future, though, the data suggests some new directions that clinical research could go in, such as an anti-CD68 monoclonal antibody perhaps.  There are some that have been identified for rheumatoid arthritis (RA) as the Kunisch paper shows below, but I don't think any are currently in commercial development at the moment.

For the moment, though, I'm left wondering more than there are answers.  

Why do people with macrophages do worse, what is the mechanism for this?  How can we best target the macrophages or the CD68 cells?  If people are screened and are found to have a poorer prognosis and are spared the exposure to chemotherapy or radiation as DeVita and Costa suggest, how should they be treated instead?

Perhaps more research will be galvanised by Steidl et al's findings.  Time will tell.


ResearchBlogging.org
Steidl C, Lee T, Shah SP, Farinha P, Han G, Nayar T, Delaney A, Jones SJ, Iqbal J, Weisenburger DD, Bast MA, Rosenwald A, Muller-Hermelink HK, Rimsza LM, Campo E, Delabie J, Braziel RM, Cook JR, Tubbs RR, Jaffe ES, Lenz G, Connors JM, Staudt LM, Chan WC, & Gascoyne RD (2010). Tumor-associated macrophages and survival in classic Hodgkin's lymphoma. The New England journal of medicine, 362 (10), 875-85 PMID: 20220182


DeVita, V., & Costa, J. (2010). Toward a Personalized Treatment of Hodgkin's Disease New England Journal of Medicine, 362 (10), 942-943 DOI: 10.1056/NEJMe0912481

Kunisch, E. (2004). Macrophage specificity of three anti-CD68 monoclonal antibodies (KP1, EBM11, and PGM1) widely used for immunohistochemistry and flow cytometry Annals of the Rheumatic Diseases, 63 (7), 774-784 DOI: 10.1136/ard.2003.013029

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