Drug Development Clinical Trial Data – Public or Private?

Posted by Judi Space on Thu,Jan 23, 2014 @ 06:00 PM

Should drug development information from clinical trials be made public or kept private? In the past, data from clinical trials of new drugs and medical devices have been the property of the companies that designed them, and they were allowed to control how and what data was released. The FDA and international equivalents research new products before granting approval, so data the company generated during drug development was up to the company to disseminate as it wished. Now, with the widely held perception that companies have only been releasing results that favored their products, the pendulum is swinging toward regulation making all data on approved drugs and devices available to the public.

The Transparency Campaigners

In Britain, the transparency initiative has been headed by the British Medical Journal, which now requires all authors of drug or device clinical trials who publish in the Journal to provide full scientific study data to anyone with a reasonable request. Also, the Cochrane Collaboration (an international non-profit) began campaigning for increased transparency when it was attempting to verify the efficacy of TamiFlu and was unsatisfied with the available data. 

These major players are joined by doctors, researchers, medical journals, and scientific societies who advocate more transparency in publishing detailed results of clinical trials and as much data about the specifics of the trials as possible. They have been pressing for this data not only going forward, but also for all medicines currently on the market.

The Drug Regulators: EU, EMA, FDA

In December 2013, the EU drafted a clinical trials regulation that will require clinical trials to be registered and results uploaded to a database that can be accessed by the public. This legislation is expected to be formally approved this year. Also, the Public Accounts Committee (of British Parliament), has issued a report this monththat calls for “full methods and results” to be released from all clinical trials, future and past.

Meanwhile, the European Medicines Agency (EMA), which is the European equivalent of the FDA, is considering a new policy on proactive disclosure of trial results, but further discussion of the issue has been tabled until March. Last year, The EMA received injunctions from both AbbVie and InterMune received injunctions against the EMA to prevent it from releasing trial data to competitors, but these injunctions were lifted last month.

In the United States, basic results of all clinical trials must now be registered in a national database that is accessible to the public (www.clinicaltrials.gov). The FDA also publishes staff reviews and other documents when it approves a new drug. However, federal laws restrict what kinds of information can be released, especially data that could reveal personal or commercially confidential information.

Self-regulation by the Pharmaceutical Industry

The European Federation of Pharmaceutical Industries and Associations (EFPIA) and the Pharmaceutical Research and Manufacturers of America (PhRMA) are fighting back by drawing up “principles for responsible data sharing” for pharmaceutical companies to voluntarily abide by. Some companies have already promised to release years of detailed clinical data upon request, in response to public relations issues.

The ABPI (Association of the British Pharmaceutical Industry) has pointed out that a peer-reviewed study it commissioned in 2013 showed a “positive trend” of increasing levels of disclosure – almost nine out of ten of all industry-sponsored trials were disclosed as of January 31, 2013.

Balancing Economic Interests with the Public’s “Right to Know”

PhRMA has argued that proposals for mandates to release all trial information go too far. “If you dump onto the sidewalk all the data, and you include commercially protected information,” he said, “then you’re essentially giving to competitors what we invested billions of dollars in.”

PhARMA claims that if the medical research industry is forced to disclose data that allows competitors to replicate their products, companies will be deterred from developing new drugs and devices that could improve quality of life for many people. On the other hand, patent protection prevents this kind of product replication. At the same time, publication bias can be used by unscrupulous members of the industry to mislead the public.

When the EFPIA/PhRMA pact was announced last year, EFPIA acknowledged that the industry was slow in affecting change. Given the exposure this topic has received recently, efforts to self-regulate may be too late to affect the groundswell of opinion in favor of legislating more transparency in drug development.

This post is based on an article by Ian Schofield – “The rising tide of trial transparency.” 


Pennside Partners is a leading pharmaceutical and biotech consulting firm with over 25 years experience. They are headquartered in the United States, the United Kingdom and Switzerland.

Tags: FDA, Drug Developers, EMA, Drug Development, Clinical Drug Trials

Adherence to Drug Regimens: Implications for Drug Developers

Posted by Judi Space on Sat,Oct 12, 2013 @ 06:00 PM

Lack of Adherence in Prescribed Medications

What if patients adhered perfectly to their prescriptions? Is simplified dosing the answer? Implications for drug developers.Approximately 50% of patients do not take their medications as prescribed.  This lack of adherence severely compromises patient outcomes and increases patient mortality and is estimated to incur costs of approximately $100 billion per year.  Some physicians believe that increasing the number of patients that adhere to their prescribed medications could have a greater effect on health than improvements in specific medical therapy. 1

However, the increasingly complicated medical regimens make it more difficult for physicians to follow Hippocrates' exhortation to “not only be prepared to do what is right himself, but also to make the patient…cooperate.”  Between 2000 and 2002, the typical Medicare beneficiary saw a median of seven physicians per year - two primary care physicians and five specialists, and typically patients recall as little as 50% of what is discussed during those visits. Although the responsibility of medication adherence is primarily on the patient, the complexity of both health care and drug regimens is causing patients to prevaricate that responsibility. 1 

The Number One Cause of Death, Yet Less Than Half Adhering to Medications

Heart disease is the number one cause of death in the United States, with 26.5 million people suffering from the disease according to the Centers for Disease Control (CDC).  Taking aspirin, cholesterol-lowering and blood pressure-lowering drugs long-term more than halves heart attack and stroke recurrence; however only 50% of patients with coronary disease and 35% in those with stroke are adhering to the medications prescribed to them. 

Is Fixed Dose Combination the Answer?

Simon Thom, M.B., B.S., M.D. of the international Centre for Circulatory Health, Imperial College London, conducted the first study to compare a fixed dose combination (FDC) medication with usual care in patients with or at high risk of cardiovascular disease (CVD).  The FDC included aspirin for blood clots, simvastatin (Zocor) for high cholesterol and two blood pressure medications. The trial of 2,000 patients showed a significant improvement in medical adherence with the use of an FDC medication for blood pressure, cholesterol, and platelet control. 

Thom found that 86 percent of the people that received the FDC kept up with their medications, compared to 65 percent of patients on the usual care.  People who began the trial with the lowest adherence had the greatest improvement – 77 percent instead of 23 percent took their medication regularly.

Overall, the FDC group also had slight declines in two major CVD risk factors - systolic blood pressure and LDL cholesterol - compared to those receiving the usual care.

More Data Needed

J. Michael Gaziano, M.D., M.P.H., cautioned, “Although the potential remains for use of various CVD polypills in certain settings, the precise advantage of this strategy remains largely unproven.  Until additional rigorous data are available that demonstrate that the polypill improves clinical CVD outcomes, it may be more important to carefully assess the multiple medications many patients currently are prescribed, often by several physicians.”

Implications for Drug Developers

Helping patients to adhere to their drug regimens will ensure that they are used, resulting in more renewed prescriptions. The time and resources invested into developing patient adherance programs will be returned with the bonus of increased sales.

 

1 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3068890/


Pennside Partners is a leading pharmaceutical and biotech consulting firm with over 25 years experience. They are headquartered in the United States, the United Kingdom and Switzerland.

Tags: Drug Developers, Drug Development

Is NICE Denying Patients the Best Treatments Available Today?

Posted by Judi Space on Sat,Oct 05, 2013 @ 08:00 AM

NICE’s Policies Under Fire

Will NICE's stringent drug approval process discourage drug developers in the UK, or is their cost-benefit approach likely to entice other countries to follow suit?The National Institute for Health and Care Excellence (NICE), an organization given the responsibility of setting the standards for high quality healthcare in the UK, has come under fire for being too conservative and resource-intensive.  In a recent opinion piece in The Times of London, business editor Ian King cautioned that the pharmaceutical industry could abandon drug development in the UK if NICE doesn’t ease its practice of restricting access to drugs based on expense or side effects.

Quoting Jonathan Emms, Pfizer UK managing director, King said that NICE turned down 40 percent of new medicines last year, advising the National Health Service (NHS) that it cannot use them or restricting their use.  Enns pointed out that “19 out of 20 attempts fail before they reach the patient – even before any NICE review,” and added, “NICE is denying patients access to some of the best treatments available today.”  

Drug Developers and the Cost of Bringing a Drug to Market

NICE CEO Andrew Dillon said that his agency is chartered with providing the NHS the best medicines available at affordable prices.  He added, “NICE is, quite properly, scrutinized closely on its decisions and the methods we use to arrive at them. We have changed and improved over the decade and more that we have been advising the NHS.  We are not perfect, but we are respected throughout the world for our quality of work.”

Dillon added, “Companies are entitled to expect a return on their investment, but health services have to be confident that the extra benefit to patients justifies the price.  It mostly does so, though sometimes at a stretch.  If we are not sure, we have to say so, in the interests of all those of us who expect the NHS to apply its resources equitably across all of the demands we make of it.”  Using the widely-quoted estimate that it now costs 1.2 billion pounds (approximately $1.9 billion) to bring a new drug to market, NICE CEO Andrew Dillon countered, “if it really does cost 1.2 billion pounds to develop a new drug, the question the pharmaceutical industry must be able to answer is this: Are you absolutely confident that it needs to.”   Dillon contends that the “research and clinical environment (in the UK) holds too many advantages for companies” to abandon the country. 

Are the UK Market Advantages Enough to Keep Drug Developers Interested?

Stephen Whitehead, CEO of ABPI, the industry body negotiating on behalf of the branded pharmaceutical industry, warns that this “advantage” in biopharmaceutical R&D is “fragile and under constant challenge,” citing that UK’s share of global clinical trials fell from 6% to 1.4% in just 10 years.  He says, “The consequences of this is the closure of six research sites in the UK over the past six years.”

Whitehead concluded, “The biopharmaceutical industry has proven that it delivers solutions to healthcare challenges but the conservative and resource-intensive approach taken by NICE adds significant cost to the development of medicines.  Through its decisions, NICE has a role in repeatedly denying patients in the UK access to medicines that are routinely available in other countries.”

Clearly, drug companies are not going to abandon the development of new drugs just because a small segment of the market will not pay for them. There is plenty of incentive from the rest of the globe. NICE is the bellwether, far out in front of other countries that are trying to impose some control over the run-away cost of new drugs. What Big Pharma really fears is that other countries, particularly in Europe will take on the NICE attitude.

What do you think will happen?  


Pennside Partners is a leading pharmaceutical and biotech consulting firm with over 25 years experience. They are headquartered in the United States, the United Kingdom and Switzerland.

Tags: Drug Developers, Drug Development, NICE

Heads up for the European Cancer Congress in Amsterdam

Posted by Judi Space on Tue,Sep 24, 2013 @ 06:00 PM

ESMO EU Cancer Congress 2013

Clinical Trial Insights

The annual European meeting offers insights into new data from ongoing clinical trials as well as a chance to discuss the implications of recently reported trial outcomes presented a few short months ago at ASCO. Pennside has reviewed the program in detail and we offer our assessment of key presentations at the meeting for drug developers and biotech.

 

Our Assessment of ESMO Key Presentations:

CRC

  • Analysis of KRAS/NRAS and BRAF mutations in FIRE-3:A randomized phase III study of FOLFIRI plus cetuximab or bevacizumab as first-line treatment for WT KRAS (exon 2) mCRC (abst#17, embargoed)
    • Data at ASCO this past June showed that there was no benefit from Vectibix for patients with NRAS mutations—it will be interesting to see if this also holds true for Erbitux in this biomarker analysis from the FIRE-3 trial.
       
  • ASPECCT: a randomized, multicenter, open-label, phase 3 study of panitumumab (pmab) vs cetuximab (cmab) for previously treated WT KRAS mCRC (abst#18, embargoed)
    • This is a head to head trial of Vectibix vs. Erbitux in the 3rd line setting—maybe one agent will come out ahead of the other, but most likely they will report similar data, possibly with some differences in safety.
       
  • Effects of regorafenib therapy on health-related quality of life in patients with metastatic colorectal cancer in the phase III CORRECT study (abst#2156)
    • TKIs have a history of poor tolerability in CRC, and Stivarga in particular was concerning because of its use in the 3/4th line palliative setting. However, this analysis appears to show that Stivarga is not detrimental to QOL, and any AEs are manageable with dose modifications.

  • Aflibercept in combination with FOLFIRI for the second-line treatment of patients with metastatic colorectal cancer: Interim safety data from the global Aflibercept Safety and Quality-of-Life Program (ASQoP and AFEQT studies) (abst#2276)
    • There is growing concern within the CRC community that while Zaltrap’s efficacy is similar to Avastin in 2nd line CRC, the tolerability is poor. The data from this study suggests that Zaltrap’s AEs are manageable and may even be lower in the real-world setting vs. the VELOUR trial. 

NSCLC

  • A phase III study of belagenpumatucel-L therapeutic tumor cell vaccine for non-small cell lung cancer (NSCLC). (LBA2, embargoed)
    • Given the recent vaccine trial failure by GSK in melanoma, we eagerly await the results of the STOP trial for belagenpumatucel-L (aka Lucanix).
       
  • Clinical activity, safety and biomarkers of PD-L1 blockade in non-small cell lung cancer (NSCLC): Additional analyses from a clinical study of the engineered antibody MPDL3280A (anti-PDL1). (3408, embargoed)
    • Key question for followers of PD-1/PD-L1: is there an efficacy/safety differences between inhibiting either target? If not – then it is a race to “first to market”
       
  • Prognostic and predictive role of kras mutations in patients with advanced non small cell lung cancer treated with docetaxel or erlotinib as second line treatment in the TAILOR trial. (LBA32, embargoed)
    • Anything new to learn regarding Kras status in NSCLC? What does a positive Kras status mean for ~20%+ of patients with adenocarcinoma? Hopefully the data will shed new light on this area rather than just casting an intriguing shadow of continued confusion for those who follow NSCLC.

BrCa

  • T-DM1 for HER2-positive metastatic breast cancer (MBC): Primary results from TH3RESA, a phase 3 study of T-DM1 vs. treatment of physician's choice (15, embargoed)
    • The TH3RESA trial may provide rationale for the use of Kadcyla in the 3rd line setting for patients who have progressed on Herceptin and Tykerb.  This trial could provide Roche with even more of a stronghold on the HER2+ disease state.
       
  • PARP inhibition with BMN 673 in ovarian and breast cancer patients with deleterious mutations of BRCA1 and BRCA2 (29, embargoed)
    • This data release will provide evidence of the potency of next generation PARPs and will, if successful provide quicker enrollment in the Phase III trial. 

PnCa

  • Additional data from the MPACT trial of Abraxane + gemcitabine vs. gemcitabine in metastatic PnCa (PET response, 2577; peripheral neuropathy, 2583; dosing, 2586)
    • Abraxane was recently approved in the US for the treatment of pancreatic cancer. These three studies will give us more information on response, side effects, and dosing.
       
  • GVAX/CRS207 (2590)
    • This is a new immunotherapy approach for the treatment of pancreatic cancer.  The Ph II study was stopped early due to positive OS results for the combination of GVAX/CRS207 vs. GVAX alone.

Melanoma

  • As it was at ASCO, Melanoma and immunotherapy will be on the hot seat again at this meeting with key presentations in the opening session: Mobilizing the Immune System to Treat Cancer (S, Topalian)
    • With hundreds of mutations extant in patients with advanced cancer, the only way to address the disease is systemically. Immunotherapies are an excellent approach, and research is bearing fruit.
       
  • Vemurafenib and MEK inhibitor, cobimetinib , in advanced BRAFV600-mutated melanoma : Dose-escalation and expansion results of a phase IB study (3703)
    • This MEK/BRAF combination is a very fast follower  of the recently approved GSK agents trametinib and dabrafenib.  Although the two GSK drugs were approved separately, data from ASCO suggests that the combo is better, and KOLs seem to agree that this will become the new standard of care. The two drugs in this study are from Roche who aims to take market share from GSK as quickly as they can. 

HCC

  • Sorafenib alone versus Sorafenib combined with Gemcitabine and Oxaliplatin (GEMOX) in the first-line treatment of advanced hepatocellular carcinoma: Final analysis of the randomized phase II GoNext trial (a UNICANCER / FFCD / PRODIGE 10 study) (2467)
    • This is an update of the previous positive data that was presented at ASCO 2013 this past June—the regimen of Nexavar and GEMOX chemo appears to be active in this population of first line HCC.
       
  • Efficacy and safety of nintedanib vs sorafenib in Asian patients with advanced hepatocellular carcinoma (HCC): A randomised Phase II trial (2580)
    • This study demonstrated that nintedanib has similar efficacy to Nexavar, but with improved tolerability.  As toxicity is a major issue in HCC due to poor patient condition, any agents with improved safety and at least equal efficacy to standard of care would be a welcome addition to the treatment algorithm.
       
  • Subgroup analysis of prognostic factors for overall survival in the SHELTER trial evaluating resminostat in advanced hepatocellular carcinoma (HCC) - the SHELTER Study Group (2601)
    • Data released earlier this month at ILCA showed the potential for a biomarker to select patients most likely to respond to resminostat, and this analysis of subpopulations from the Ph I/II SHELTER study of resminostat alone or in combination with sorafenib may help further define the ideal patient population for this developmental HDAC inhibitor. In particular, the combination of resminostat and sorafenib shows encouraging activity in second line patients who progressed on prior sorafenib.

ThyCa

  • Progressive, metastatic medullary thyroid cancer: Baseline symptoms and disease characteristics among patients enrolled in the EXAM trial (3154)
    • The results from this analysis of the EXAM trial of cabozantinib in medullary thyroid cancer suggest that, despite the common perception that this is an indolent tumor, many patients that present with radiologic findings of progressive disease actually have high disease burden and related symptoms. This justifies approval of two targeted agents in MTC (cabozantinib and vandetanib), as many patients will inevitably need an efficacious therapy once they reach the point of high disease burden.
       
  • Association between tumor BRAF and RAS mutation status and clinical outcomes in patients with radioactive iodine (RAI)-refractory differentiated thyroid cancer (DTC) randomized to sorafenib or placebo: Sub-analysis of the phase III DECISION trial (3155)
    • This biomarker analysis of the DECISION explored the effect of RAS and BRAF mutations on benefit from Nexavar. While all patients, regardless of mutational status, appeared to benefit from therapy, those with RAS mutations had lowered PFS, while patients with BRAF mutations had improved PFS. Since all patients benefitted from Nexavar, it is unlikely that these biomarkers would be used to select patients for therapy, but important to know that the benefit exists regardless of mutational status.
       
  • An open-label, multi-center phase 2 study of the BRAF inhibitor vemurafenib in patients with metastatic or unresectable papillary thyroid cancer positive for the BRAF V600 mutation and resistant to radioactive iodine (28, embargoed)
    • There is a lot of excitement surrounding the use of BRAF inhibitors in patients with BRAF V600 mutated thyroid tumors. This late-breaking abstract for vemurafenib will be a first look at the potential promise of these agents in RAI-refractory thyroid cancer. 

GBM

  • Bevacizumab, irinotecan and radiotherapy versus standard temozolomide and radiotherapy in newly diagnosed, MGMT-non-methylated glioblastoma patients: Updated results from the randomized multicenter GLARIUS trial (3300)
    • This is an update of the data presented at ASCO 2013 this past June. Again, it appears that Avastin/irinotecan therapy prolong PFS in patients with MGMT non-methlyated GBM, where SOC TMZ therapy is ineffective and an active regimen is needed.
       
  • Efficacy and safety of bevacizumab (Bv) plus standard combination temozolomide (T) and radiotherapy (RT) in newly diagnosed glioblastoma: Final results from AVAglio (3301)
    • An update of the AVAglio data presented at ASCO—final OS data will be presented at the meeting. The additional data coming at ESMO may help clarify the role of Avastin in GBM, where data has been inconsistent. 

STS

  • PICASSO 3: A phase 3 international, randomized, double-blind, placebo-controlled study of doxorubicin (dox) plus palifosfamide (pali) vs. dox plus placebo for patients (pts) in first-line for metastatic soft tissue sarcoma (mSTS) (3802)
    • The failure of the PICASSO trial once again shows the need for more targeted trial designs in Soft Tissue Sarcoma.  KOLs continue to press for better targeted trials in this difficult group of diseases.
       
  • Final results of sequential phase 2 studies of palbociclib
    (PD0332991) in CDK4-amplified liposarcoma  (3826)
    • The use of CDK4 amplification as a biomarker may provide palbociclib with a targeted approach in Sarcoma that will prove effective.  The Phase III trial is being planned. 

NET

  • A randomized, double-blind, placebo-Controlled study of Lanreotide Antiproliferative Response in patients with gastroenteropancreatic  NeuroEndocrine Tumors (CLARINET). (LBA3, embargoed)
    • IPSEN has announced that lanreotide has meet it’s primary endpoint in the CLARINET and ELACT trials.  The presentation on Saturday should give us insights into the robustness of the data and an expectation for ELECT at ASCO GI in January, 2014.  


Pennside Partners is a leading pharmaceutical and biotech consulting firm with over 25 years experience. They are headquartered in the United States, the United Kingdom and Switzerland.

Tags: Drug Developers, Cancer Drug Development, Drug Development, Breast Cancer Drug Development, Breast Cancer Oncology, ASCO, ESMO

Pharmaceutical Marketing Cutbacks, Doctors Getting Squeezed

Posted by Chris Burns on Mon,Apr 29, 2013 @ 10:00 AM

Two of the biggest pharmaceutical companies, Pfizer Inc. and GlaxoSmithKline, are significantly reducing spending with doctors for events at which doctors make presentations to their peers. Combined with cutbacks in spending on meals during lunchtime presentations by drug makers, doctors are feeling the financial impact. 

Increased Scrutiny of Pharmaceutical Marketing Practices - Will it Affect Drug Development?

Pharmaceutical Marketing Changes - Payments to Doctors Down SignificantlyPfizer and GlaxoSmithKline have cut spending on dinners and other events where expert doctors are paid to give presentations to peers about drugs and diseases as part of the pharma companies' drug development and marketing efforts. An increase of layoffs of pharmaceutical sales representatives and patent expirations for big-selling drugs are resulting in fewer sales calls and fewer free lunches provided to physicians’ offices.

There is increased scrutiny on the relationship between the pharmaceutical companies and the doctors who prescribe their drugs over concerns the perks may affect doctors’ prescribing patterns. The Sunshine Act included in the 2010 US healthcare overhaul requires drug companies and medical device makers to report doctor payments to the federal government for later posting of the information online.

Reported Cutbacks in 2012

The cutbacks listed below are difficult to accurately compare among companies as some use different criteria for reporting and many have changed their criteria in 2011 thereby making year-over-year comparisons difficult to assess.

    • Pfizer: 40% reduction on doctor meals- due to an increase in “virtual meetings” many meals can be avoided (Spokeswoman Sharon Castillo) 
       
    • Pfizer: total payments reduced from $173.2 million, down 11% from 2011. Most payments were related mainly to clinical research, which stayed flat.
       
    • Eli Lilly & Company: 30% reduction in US sales force while facing the loss of patent protection on two top-selling drugs. 
       
    • GlaxoSmithKline: 20% reduction in payments to US physicians (skewed partially due to a change in reporting criteria) to 97.1 million, reflecting a reduction in the need to fund speaker programs in recent years found through yearly re-evaluation. 
       
    • Teva Pharmaceutical Industries Ltd.'s TEVA-0.69% Cephalon unit reduced payments to health care professionals in 2012 by nearly 11% to $28.1 million.
       

Pfizer’s Cuts Based On Loss of Exclusivity

Pfizer cut more than 60% of its spending on expert-led forums including events where company-paid doctors discuss Pfizer drugs or certain diseases.  Cut from 1,539 health-care professionals speaking to peers 3,569 in 2011, average payments declined to $5380 from $6110. This drop was partially related to loss of exclusivity for drugs like Lipitor triggering low-cost generation generic competition. Pfizer also attributes the decline in spending on speaker programs to “more efficient ways to deliver educational materials and evolving approaches to meet physicians’ information needs.”

The Drive for Transparency in Pharma Company Payments to Doctors

According to Allan Coukell, deputy direction of medical programs for the Pew Charitable Trusts, “It is possible the trend we’ve seen for a few years toward increasing focus on payments will continue, and both providers and companies” will re-examine some of these financial relationships.

Drug makers claim payments are needed to compensate doctors who advise, assist in research and clinical trials, and educate other doctors about drugs and diseases. However, proponents of transparency are concerned with the patients’ knowledge of money doctors receive for prescriptions from the makers of drugs they provide.

Major changes in doctor compensation from pharmaceutical companies include:

    • 44 medical schools ban/restrict faculty participation in speaker’s bureaus (AMSA reports)
    • Commercial support for continuing medical education –needed for doctors to maintain licenses- has trended downwards
    • Industry influence is waning due partly to limitations on what medical school faculty and students can accept from companies
       

Doctors Concerned Over Payment Disclosures

Some doctors fear inaccurate or misleading data to will be posted online by the Federal government.  Of 1,000 doctors surveyed by MMIS Inc. and Healthcare Data Solutions, 63% showed concern regarding public disclosure and 21% said they would sever relationships with manufacturers reporting inaccurate information.

Some Companies Showed Increased Spending

    • AstraZeneca PLC- showed increases of about 2% to $30.6 mission million including consulting fees, speaker fees and meals but not clinical research
    • Johnson & Johnson- Some pharmaceutical divisions report increases by 15% to $27 million attributed to J&J’s scientific educational activities

The above post is a condensed and edited summary of an article appearing in the Wall Street Journal online on April 12, 2013.


Pennside Partners is a leading pharmaceutical and biotech consulting firm with over 25 years experience. They are headquartered in the United States, the United Kingdom and Switzerland.

Tags: Drug Developers, Drug Development, Pharmaceutical Marketing

Momentum for Biosimilars is Building. What’s Next?

Posted by Tom Penrice on Tue,Apr 23, 2013 @ 06:00 PM

Overview:
Both the FDA and the EMA are showing increasing levels of support for biosimilars, while physician resistance is declining in both the US and Europe. Cost is a big driver, among other factors.[1]

Biosimilar Drug Development Trends in Europe – Timing is Everything

Biosimilar drug development trends in US and European pharma drug development industryResistance to biosimilars in Europe is declining just as patents are expiring on many highly lucrative biologics, among them Herceptin (trastuzumab), Remicade (infliximab), and Rituxan (rituximab).  Significant cost advantages, important regulatory changes, and a growing openness to new methods of scientific analysis have combined to drive the trend.  Although the financial performance of biosimilars has been disappointing to date, nevertheless the perceived opportunities are attracting innovators and new players.

Why the Resistance to Lower Cost Biosimilars?

Resistance to date has been due primarily to two factors: pushback from physicians reluctant to switch patients to a biosimilar drug, and the lack of a systematic way for pharmacists to easily substitute a biosimilar for an originator drug.  As a result, the returns from biosimilars in Europe have been unimpressive to date. 

Meanwhile, in the US the FDA has yet to receive its first biosimilar application, despite the fact that for two years a regulatory pathway has been provided.  Innovator lobbying at the state level is a major factor contributing to the quagmire, whereby bills are being pushed to make it more difficult for automatic substitution of biosimilars for branded biologics to take place.

Doctors Signing On – Slowly

Unlike the FDA in America which has decision making power for all 50 states for such issues,  the EMA must leave it to each national government to make their own rulings on biosimilars.

In Norway, physicians are slowly growing more positive toward biosimilars partly due to price, a growing factor given sluggish European economies and rising health care costs, according to a cardiologist and medical director at Norway’s regulatory agency.

Economic incentives to prescribe cheaper drugs are also affecting physician acceptance of biosimilars in some northern European countries. For example, in Germany prescription quotas for generic drugs are imposed on physicians as a way to keep within allocated budgets. It is also helpful that Germany has declared copycat EPO’s to be the equivalent of the originals. Although not legally binding, these quotas in Germany have contributed to copycat EPO penetration growing from 30% to 39% in the past three years.[2]

Biosimilars - Impact on Price and Profits

The downward pressure on price due to the growing adoption of biosimilars has resulted in innovators making deep price cuts in order to retain market share, including with hospitals. As a result, payers are enjoying the savings.  Savings in Germany are estimated at over €1 billion per year by 2017.

Changing Definitions and Perceptions

EMA is increasingly accepting biosimilars due in part to recognizing that analytical science gains have made it possible to supply proof of similarity without requiring the time and expense of clinical data.  Last year EMU changed it’s description of biosimilars from products deemed “similar but not identical” to one stating, “the active substance of a biosimilar and the reference medicine is essentially the same biologic substance, though there may be minor differences”, thereby making it more difficult for innovators to make the case for their originals. 

FDA More Open to Biosimilars?

The FDA, while arriving late to the game, may be more open to biosimilars than EMA in terms of an easier acceptance of the analytical science argument for determining similarity. By comparison, the EMA appears to rely more on a clinical trial mindset. The US approach has not been without its rewards, as competition and savings can be significant. According to IMS Health, the US health care system has saved $1.6 billion since launch on Sandoz / Momenta Pharmaceuticals Inc.’s m-enoxaparin, the first of two competing complex copies of Sanofi’s Lovenox (enoxaparin).

Long Term Impact of Biosimilars on the Pharma & Biotech Industry

Now that payers are alert to the cost savings potential of biosimilars, there can be little doubt that the pressure to drive down prices will continue unabated. Indeed, the payers, especially the government payers, have the capability to change the game very quickly.

If prices and profits were to drop sharply and frequently for originals due to growing inroads made by biosimilars, one must wonder to what degree investment in research by innovators may suffer.


[2] http://www.elsevierbi.com/publications/the-pink-sheet/75/6/germany-may-need-to-jump-start-its-stagnant-biosimilars-market 


Pennside Partners is a leading pharmaceutical and biotech consulting firm with over 25 years experience. They are headquartered in the United States, the United Kingdom and Switzerland.

Tags: Pharma Brand Strategy, FDA, Drug Developers, Biosimilars, Health Care Costs, EMA

NCI Improvements: Drug Development Opportunity for Pharma and Biotech

Posted by Judi Space on Tue,Mar 12, 2013 @ 06:00 PM

Three years ago the Institute of medicine declared that the nation’s cooperative group system for conducting clinical trials was so moribund as to not be an effective vehicle for the generation of scientific data in a timely fashion. In a report generated in 2010, the IOM recommended that the number of cooperative oncology groups be reduced from 10 down to 5[1], improve speed and efficacy of the trial processes as well as incorporate new scientific discovery into clinical protocols. Along with this, the report said it was critical to create a data platform that would assist in the administration of trials across all of the remaining cooperative groups. This would be a system to which both large academic centers and community cancer centers could adhere.

NCI Less of a Barrier; More of a Facilitator

To a large extent, the NCI was  a barrier to the conduct of clinical trials due to their role of providing oversight. The IOM report urged that NCI become part of the solution by helping to prioritize and design trials as well as directing patients to relevant studies so that enrolment could proceed more rapidly. In addition, CMS was tasked with removing barriers to enrollment by supporting appropriate costs associated with patient treatment during the trials.

Efforts Bearing Fruit

Now, nearly three years later, we can see the effects of this report. In a two day workshop[2] that took place in Washington last month, improvements in the national cooperative group trial system were documented[3]. Among the improvements noted:

  • The time between concept and activation of phase II trials sponsored by NCI has shrunk by more than a third. Trials not meeting timelines will be terminated!
  • Time to activation for phase III trials has been halved since the overhaul process began
  • The number of cooperative groups has actually been cut in half – now there are only 5
  • A common enrollment and data management system has been put into place
  • Patients can enroll 24/7 and they may participate in ANY Ph III trial in the system regardless of origin
  • There are now  standardized agreements for industry collaborations
  • A new  review process has been launched for grading the quality of trials
  • Integrated biospecimen banks are being created

Still to come are more innovative Ph II trials based on molecular biology of the tumors and the extensive use of biomarkers and genomic profiling.

Ecology of Clinical Trials

Community Cancer Centers are Key

The key to moving clinical research forward more rapidly will be enhanced participation of community cancer centers. Investigators at these sites are often hesitant to take part as many of the costs associated with the trials are not covered.  After more provisions of the Affordable Care Act go into effect, next January, this may no longer be a barrier. Federal law will require insurers cover the cost of routine patient care in clinical trials.

Design and Conduct of Trials Improving in UK As Well 

Interestingly, the US is not the only place that has had a sea change in the way it conducts clinical research for cancer. Over the same period, the UK’s National Health Service has recognized that clinical research is an important part of its mission, and therefore has provided incentives for patients to participate in trials. The key here is that cancer patients do not get access to novel agents unless they participate in the trials. The result is a trials network that rivals anything in the US but existing in a much smaller country.

 

Implications for Drug Development:

Drug approval process improving in the UK as well as the US

Pharma  and biotech companies can harness the power of the NCI to get things done faster than they have become accustomed to in the past, and the improvements will continue into the foreseeable future. This is also good news for cancer patients who will be able to access more cutting edge clinical trials no matter what part of the country they are from.

 


[1] http://www.iom.edu/~/media/Files/Report%20Files/2010/A-National-Cancer-Clinical-Trials-System-for-the-21st-Century-Reinvigorating-the-NCI-Cooperative/NCI%20Cancer%20Clinical%20Trials%202010%20%20Report%20Brief.pdf

[2] http://www.iom.edu/~/media/Files/Activity%20Files/Disease/NCPF/2013-FEB-11/Agenda%20-%20IOM%20ASCO%20Implementation%20Workshop.pdf

[3] http://www.nap.edu/catalog.php?record_id=18273


Pennside Partners is a leading pharmaceutical and biotech consulting firm with over 25 years experience. They are headquartered in the United States, the United Kingdom and Switzerland.

Tags: FDA, Drug Developers, Oncology, Predictive Biomarkers, Targeted Therapy, Data Standardization, NCI, Cancer Drug Development, Oncology Clinical Trial Design

ASCO GU: Heads-Up for Biotech Drug Development in Kidney Cancer

Posted by Marne Wessner on Mon,Feb 11, 2013 @ 11:50 PM

Interesting Data for Pharma and Biotech Drug Developers

ASCO GU2 2013 Genitourinary Cancers Symposium for Pharma and Biotech Drug DevelopmentASCO’s second meeting of the year, ASCO GU, is coming up next week, and here is our list of anticipated data releases for renal cell carcinoma.  (Note that full abstracts won’t be available until February 12, so it is impossible to comment on the significance of these results until then.) It looks to be a quiet meeting this year for RCC, according to key opinion leaders, but there are some presentations on the schedule with the potential for interesting data for Pharma and Biotech drug developers.

Additional Data from TIVO-1 Trial of Aveo/Astellas’ Tivozanib

There are several abstracts reporting aspects of the TIVO-1 trial data at this year’s meeting. OS, subgroup analyses, and quality of life data are of high interest, and two additional poster presentations will also address biomarker research and tivozanib efficacy in patients previously treated with Bayer’s Nexavar (sorafenib).

Emerging Immunotherapies

Immunotherapy is an exciting field in RCC. The latest generation of immunomodulating agents includes nivolumab, an anti-PD1 from BMS; and AGS-003, a dentritic cell therapy from Argos—both in Ph III for RCC. These agents each have poster presentations, which will hopefully give early indications about their potential in RCC.

Sequencing and Combinations of Approved Therapies for Kidney Cancer

The hottest issue in RCC therapeutics is the sequencing of the many approved agents on the market, and the positioning of any new ones about to be approved. This is a conundrum for oncologists as well as drug developers seeking to leverage the data to gain market share.

  • Votrient: Additional quality of data from the COMPARZ trial of GSK’s Votrient (pazopanib) vs. Pfizer’s Sutent (sunitinib) in first line RCC will report, likely an update of what was reported at ESMO 2012 last fall.
     
  • Inlyta:  Pfizer announced that the AGILE 1051 trial of Inlyta (axitinib) in first line RCC did not meet its primary endpoint in October 2012, and it looks like we will finally see data from that trial as well as the Ph II dosing trial in first line RCC.
     
  • Avastin combos: The Ph II BEST trial, which compared Roche/Genentech’s Avastin alone and combinations of Avastin, Nexavar, and Torisel, will also report data. In RCC, combinations of currently-approved targeted agents have been unsuccessful historically, so expectations are low for this trial.
     
  • mTOR inhibitors: Finally, a new safety analysis of mTOR inhibitors will be presented, which will hopefully provide oncologists with more information on dealing with the side effects of this class of drugs, which are very different from the tyrosine kinase inhibitors that are commonly used in RCC.

 

Key Presentations of Interest at ASCO GU

  1. Overall survival results from a phase III study of tivozanib hydrochloride versus sorafenib in patients with RCC (Motzer, et al, abstract 350)
     
  2. Subgroup analyses of a phase III trial comparing tivozanib hydrochloride versus sorafenib as initial targeted therapy for patients with mRCC (Hutson, et al, abstract 354)
     
  3. Treatment benefit of tivozanib hydrochloride versus sorafenib on health-related quality of life among patients with advanced/mRCC: Tivo-1 study results (Cella, et al, abstract 355)
     
  4. Axitinib vs. sorafenib as first‑line therapy in patients with mRCC (Hutson, et al, abstract LBA348)
     
  5. Quality of life among patients with RCC treated with pazopanib versus sunitinib in the COMPARZ study (Cella, et al, abstract 346)
     
  6. Axitinib with or without dose titration for first-line mRCC: Unblinded results from a randomized phase II study (Rini et al, abstract LBA349)
     
  7. The BEST trial (E2804): A randomized Ph II study of VEGF, RAF kinase, and mTOR combination targeted therapy with bevacizumab, sorafenib, and temsirolimus in advanced RCC (McDermott et al, abstract 345)
     
  8. Incidence and risk of treatment-related mortality in patients with RCC and non-RCC treated with mTOR inhibitors (Choueiri, et al, abstract 347)
     
  9. Clinical activity and safety of antiPD-1 (BMS-936558) in patients with previously treated mRCC: An updated analysis (McDermott, et al, abstract 351)
     
  10. Prolonged survival with personalized immunotherapy (AGS-003) in combination with sunitinib in unfavorable risk mRCC (Amin, et al, abstract 357)


Pennside Partners is a leading pharmaceutical and biotech consulting firm with over 25 years experience. They are headquartered in the United States, the United Kingdom and Switzerland.

Tags: Drug Developers, Targeted Therapy, Drug Development, Kidney Cancer, Biotech Consulting, Pharma Launch Planning

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