Pharma Strategy Blog

Commentary on Pharma & Biotech Oncology / Hematology New Product Development

Posts tagged ‘Seattle Genetics’

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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Antibody Drug Conjugates (ADCs) in cancer research: what are they?

By on May 25, 2011

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!

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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.

Brentuximab Vedotin (SGN-35) for Relapsed CD30-Positive Lymphomas

By on November 4, 2010

This morning I was delighted to see that one of my favourite medical doctors on Twitter, Dr Anas Younes from MD Anderson, has published a paper in the New England Journal of Medicine on a clinical trial of a promising new agent in development for a particular type of lymphoma.

Dr Younes is very active in social media on Twitter and Facebook and has garnered quite a following of lymphoma patients interested in learning about new treatments for the disease.   This also means that patients and caregivers following him are able to find out about new clinical trials as they open up.  MD Anderson Cancer Center probably has access to more clinical trials across all tumour types than any other cancer center, offering lots of options for cancer patients to receive novel therapies that may help their condition.   Another benefit of a physician being involved with social media is that awareness of the trials will reach more people this way and hence probably accrue faster.

What’s new in Hodgkins Lymphoma?

Before we discuss the NEJM paper, the other side of social media is that MD Anderson also use it to communicate the results of their trials on the Institution website and Dr Younes also has a nice video for patients, explaining how the drug works, about the trial and the results that they found.

Now, this was a phase I trial so normally we wouldn’t expect to see too much from an efficacy standpoint, as the main goal of these studies is to assess the range of toxicities and determine the maximum tolerated dose (MTD) for phase II trials, which look at the efficacy signal in more detail.

That said, what Dr Younes and his colleagues found was quite impressive responses in a disease that has not seen much in the way of new treatments for more than a decade.

It should be noted that the agent targets CD30 antigen that is expressed on Hodgkin Lymphoma and anaplastic large-cell lymphoma (ALCL) cells.  Previous attempts to target the CD30 antigen with monoclonal-based therapies have shown minimal activity.  What’s different about this new agent is that it is an antibody-drug conjugate (ADC), with an anti-CD30 monoclonal antibody linked to monomethyl auristatin E (MMAE), an anti-cancer agent.

The drug they were evaluating, brentuximab vedotin (SGN-35), from a partnership between Seattle Genetics and Millennium, elicited complete responses (CR) or partial responses (PR) in 38% of the patients with Hodgkin Lymphoma (HL).  In the NEJM article it boldly stated that:

“The median duration of response was at least 9.7 months. Tumor regression was observed in 36 of 42 patients who could be evaluated (86%).”

Looking at the data in the article, what was amazing was that there were 17 objective responses (38%), 11 of which (25%) were complete remissions, which essentially means disappearance of all evidence of the disease.  In addition, CT scans showed that 36 of 42 (86%) of evaluable patients saw their tumours shrink.

What’s next?

Overall, I think these very promising results raise hopes that the phase II trial will also produce positive results at the American Society of Hematology (ASH) in December, which will be really great news for patients with Hodgkin Lymphoma.

If the phase II results also look positive, then we can probably expect Seattle Genetics and Millennium to file in the first half of 2011.

ResearchBlogging.org Younes, A., Bartlett, N., Leonard, J., Kennedy, D., Lynch, C., Sievers, E., & Forero-Torres, A. (2010). Brentuximab Vedotin (SGN-35) for Relapsed CD30-Positive Lymphomas New England Journal of Medicine, 363 (19), 1812-1821 DOI: 10.1056/NEJMoa1002965

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Interesting new data at ASH for cancer biotech Seattle Genetics

By on December 10, 2008

There have been a number of interesting early phase compounds with new data being reported at American Society of Hematology (ASH) meeting this weekend, some of these will be described over the next few days.Seattle Genetics has a number of monoclonal antibodies in development for the treatment of hematologic malignancies.  One of them, SGN-35, is an antibody conjugate that targets CD-30 cells and hence is being evaluated in CD-30 positive malignancies such as Hodgkins Lymphoma.  There was an interesting poster published here (PDF) at the ASH meeting.

Lintuzumab is a humanized monoclonal antibody that targets the CD33 antigen, which is expressed on a number of hematologic malignancies, including AML, myelodysplastic syndromes (MDS) and several myeloproliferative disorders.  Seattle Genetics recently reported data from a completed phase Ia dose-escalation clinical trial of lintuzumab demonstrating multiple complete responses at well-tolerated doses. In addition to the phase IIb clinical trial, the company is also conducting a phase Ib trial of single-agent lintuzumab in patients with AML or MDS and a phase I trial of lintuzumab in combination with Revlimid(R) (lenalidomide) for advanced MDS. 


The Independent Data Monitoring Committee (IDMC) has now completed a pre-specified safety review of data from the ongoing phase IIb trial of lintuzumab (SGN-33) in combination with low-dose cytarabine chemotherapy for older patients with acute myeloid leukemia (AML). 

After review of the collected data, the IDMC did not identify any safety concerns and has recommended that the trial continue per the protocol. This interim assessment was based upon a planned evaluation of safety data from the first 50 percent of patients randomized in the study who received at least one dose of treatment. The company has completed approximately two-thirds of the total target enrollment of 210 patients, and expects to report data in the first half of 2010. 

Another drug from the same company, SGN-40 (dacetuzumab), is being tested b-cell lymphomas (PDF of poster) and multiple myeloma and was snapped up early by Genentech in a licensing deal in 2007.  Seattle Genetics also has a monoclonal antibody in development for autoimmune diseases (SGN-70 and SGN-75), which target CD70.  The latter is in preclinical development at present.

It should be an interesting company to watch out for.

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