News

Food for Thought: The Future of Biosimilars

On June 8, the Society of Investment Professionals in Germany (DVFA) and its Life Science Committee hosted its annual conference which this time focused on biosimilars. The event covered key scientific topics, regulatory pathways and commercial issues of the market.

While experts agreed that the US will soon follow the EU in establishing a regulatory pathway for filing and approval of biosimilars – with a few originator companies still taking rearguard actions – it is not yet evident whether biosimilars will conquer the markets simply because of lower prices. In many EU countries, there will be no automatic substitution as with small molecule generics so that doctors need to be convinced to prescribe a particular “branded” biosimilar.

However, while the regulatory pathway is based on comparability, this claim cannot be made for marketing as Adem Koyuncu, Partner of Mayer Brown LLP explained. He said, it will constitute a case for litigation to claim that safety and side effect profiles of a biosimilar are the same as those of the originator product as these features have not been demonstrated to the same extend during the approval procedure. So the question for marketing is to educate practitioners and patients on biosimilars as an “alternative”, not as “substitute”. In fact, as Frank Pieters of Teva Pharmaceuticals said, it may be advisable, depending on the product and the environment, to develop hybrid marketing models, mixing “generic” and “branded” approaches.

Gertraud Unterrainer of ProBioGen explained the intricacies of developing cells lines for the production of biosimilars: the goal is to aim for the closest possible match to the originator product, not for a product that might be regarded as superior, e.g. in respect to the amount of impurities. She also stressed that activity assays are not a substitute for assessing the clinical impact of differences.

With all these details being tricky, both Falk Ehmann of the European Medicines Agency (EMEA) and Christopher Klein of Sandoz International do not expect imminent fierce competition from the many Asian and Indian companies developing biosimilars. “They can market their products in Europe,” Ehmann said, “however, they have to meet all our standards and requirements to get approval.”

Last but not least, Manfred Ruediger of LSP Life Science Partners said that as a VC, he is still refraining from investing in biosimilar companies as he still is not convinced on the investment multiples that can be reached with biosimilars within ten years time.

A link to the presentations will be available shortly here.

Food for Thought: Simply Obscene

In a recent article (“Simply Obscene”) the influential German news magazine “Der Spiegel” (20/2010, May 17, 2010) stated the pharma industry was using “with the unscrupulousness of a stock jobber” a loophole in Germany’s highly regulated health care system to charge extremely high prices for basically useless cancer medications. In particular, the article featured Yondelis by Pharma Mar, Nexavar by Bayer, Hycamtin and Tyverb by GlaxoSmithKline, Erbitux by Merck KGaA, Sutent by Pfizer, Iressa by AstraZeneca, Avastin, Xeloda, Mab-Thera and Herceptin by Roche and Alimta by Lilly as examples for cancer drugs providing only marginal survival benefits at enormous costs and stated this was “lawful looting of the health care system”.  The only exception according to the authors of the article was Novartis’ Gleevec.

This week, the Competence Network Malignant Lymphomas published an open “letter to the editor”  (only available in German) stating that in the case of lymphoma therapy the authors of the article had done “obviously sloppy work”: “Therapy costs of lymphocyte-specific antibody Rituximab [MabThera] amount to €24,000, not €134,000 per year. Several independent studies have demonstrated that overall survival in both follicular and diffuse large B cell lymphoma is prolonged on average by several years (!), in fact without substantial side effects.” Der Spiegel had stated extension of survival in these two indications was “not proven”.

The letter also said that administrative costs for studies to optimize therapies had increased by a a factor of 10 in the last couple of years due to legal requirements.

The article of Spiegel magazine is available online in German, however without the tables featuring treatment costs and extension of survival for the drugs mentioned.

Food for Thought: The Landscape of Selection Biomarkers in Oncology Trials

Hundreds of clinical trials in oncology already use biomarkers to identify patients who have a higher or lower risk of disease progression, as well as help predict how patients will respond to different treatments. However, there has been no systematic overview on the landscape of biomarker use in oncology trials.

In this week’s Science Translational Medicine Robert Sikorski and Bin Yao present the results of their laudable and laborious task to analyse the public database ClinicalTrials.gov for this kind of information.

Their findings can be summarized as follows:

(1) More biomarker work is done in less frequent tumors (such as leukemias) than in more frequent types such as prostate cancer, so it seems that not the big cancer indications will be the first to become segmented into smaller populations with etter treatment options.

(2) There are relatively few selection biomarkers for the major solid tumor indications that will enter clinical practice through current Phase III trials. However, as the database does not include retrospective analyses of completed trials, this point is difficult to assess.

(3) Implementation of biomarkers in clinical trials adds a substantial layer of complexity, increasing costs and making intertrial comparisons more difficult.

(4) Next-generation approaches that apply whole-cancer genome analysis to identify changes associated with therapeutic response will increasingly serve as a major disruptive force reshaping the cancer biomarker landscape.

They forecast that the future of oncology trials will be the study of biomarker-defined patients in smaller, randomized Phase III trials. In addition, they conclude that it should be feasible soon to obtain the complete profile of DNA alterations, DNA copy number changes, and even DNA methylation patterns within a tumor for all subjects in phase I and II studies.

“The resulting ability,” the authors write, “to target new treatments by tumor molecular signatures early in drug development is transformative and offers the promise of demonstrating significantly greater clinical utility with smaller study populations.”

Food for Thought: Why tissue sample quality matters for personalized medicine

“We now have the technical ability to get the wrong answers with unprecedented speed.” Carolyn Compton, Director, Office of Biorepositories and Biospecimen Research

When the U.S. National Cancer Institute recently started its Cancer Genome Atlas initiative and asked biobanks all over the world for cancer biopsy samples, it was puzzled to find that the quality of the donated samples was so poor that the NCI was unable to meet the moderate target of collecting 1,500 biopsy samples per cancer. In a telling article in “Wired magazin”, Steve Silberman gives the example of a university biobank, which claimed to have more than 12,000 samples of glioblastoma in its collection. However, the initiative judged only 18 of those as good enough to use. After contacting biobanks on a global scale, the researchers did not even get to 500 glioblastoma samples of satisfactory quality and barely got to 500 in ovarian cancer, the 5th most common cancer in women. In lung cancer, the initiative was unable to start because it simply could not obtain the minimum number of biopsy samples of adequate quality. „However, all biobanks thought they were doing a superb job,“ resumed Carolyn Compton, director of NCI‘s Office of Biorepositories and Biospecimen Research OBBR and responsible for the biopsy sampling part.
The reason for the poor quality is simple: minutes after cutting tissue off from blood supply, cells start to react with massive changes in gene methylation patterns, gene expression and translation, proteome composition, enzymatic activities, surface protein patterns, etc. The changes affect hundreds of genes, and it is reality in many hospitals that the resected cancer tissue lies around for hours at room temperature in the operation theater before it is put in the freezer to get formalin-fixed a few days later.
Even more, the medication the patient has been given prior to or during operation (sedatives, anesthetics, etc.) has a profound impact on these parameters as well.
Therefore, very often it is impossible to judge whether the changes observed between individual patients is a result of their inherently different metabolisms/genetic makeup or a consequence of different sampling and handling of the biopsies and medications.
“We now have the technical ability to get the wrong answers with unprecedented speed,” Compton says. “If we put the wrong stuff into the front end of our analytical pipeline, we will not only lose the war on cancer, we’ll pollute the scientific literature with incorrect data that will take us a long time to sort out. This is a crisis that requires disruptive innovation.”
OBBR is now systematically looking into the problem and has chosen one company to perform the first systematic studies: Hamburg-based Indivumed GmbH. The company did pioneering research and devised standards for cancer biopsy samplings that are applied in a network of clinics Indivumed is collaborating with in the Hamburg and the Washington DC area. The company runs the only ISO-certified biobank in the world and is offering biospecimens, related patient data, and services including biomarker development for the purpose of developing personalized cancer therapies. By employing specially trained nurses, the company guarantees that each sample is frozen or fixed within 12 minutes, and each sample comes with a data package comprising several hundred data on the patient‘s medical history and life style. Further information about Indivumed, a client of akampion, can be found here.

1 … 181 182 183 … 189