Heads up for ASCO: Our List of Key Oncology Presentations

Posted by Judi Space on Tue,May 07, 2013 @ 06:00 PM

Expect the biggest data dump of the year at this annual cancer mega-conference

ASCO Oncology and Drug Development Conference Highlights May June 2013

 

 

 

For those of us taking an interest in Biotech and Drug Development the largest release of new clinical data is just around the corner at the annual American Society of Clinical Oncology (ASCO) meeting to be held in Chicago starting on May 31. In ASCO’s preliminary press release, the organization revealed what it thought were the key presentations to be presented at the meeting.  The actual abstracts will be posted on the ASCO website on May 15th, but the titles of the presentations are available now.

Pennside always sends a large team to ASCO to review the data and discuss its implications with experts in the field.  After reviewing the entire program, we have a hit list of what we believe are the most important studies to be presented at the meeting, especially regarding development of targeted therapies for a number of cancer indications.

Breast Cancer:

    • Phase III, randomized, double-blind, placebo-controlled multicenter trial of daily everolimus plus weekly trastuzumab and vinorelbine in trastuzumab-resistant, advanced breast cancer (BOLERO-3). (Abstract #505)

One of the most important data releases this year at ASCO in Breast Cancer will be the preliminary results from the BOLERO-3 trial of Afinitor in combination with Herceptin and vinorelbine in HER2+ metastatic Breast Cancer patients.  Results were expected at the San Antonio Breast Cancer Symposium in 2012; however there had not been enough events to report at that time.  This trial should clarify whether Afinitor can be used to reverse resistance to HER2 therapies as well as it does with hormonal therapies.  If successful, this will expand the reach of Afinitor into the 2nd line of HER2+ Breast Cancer therapy, where its side effect profile will not cause the hesitance that it has in the ER+ populations.

  • A phase II trial of an oral CDK 4/6 inhibitor, PD0332991, in advanced breast cancer. (Abstract #519)

Interest remains extremely high for the anti-CDK4/6 inhibitor palbociclib from Pfizer.  More data from the Phase II trial will be released during a poster discussion session at ASCO.  The preliminary data seen at SABCS in 2012 was very significant and if these further results support it, the approval of this compound will dramatically affect the 1st line treatment of advanced ER+ Breast Cancer.   Since the FDA granted palbocicllib the designation of Breakthrough Therapy, the oncology community is very focused on how this will affect it’s developmental pathway. 

Colorectal Cancer:

  • Analysis of KRAS/NRAS, BRAF mutations in the phase III PRIME study of panitumumab plus FOLFOX versus FOLFOX as first-line treatment for mCRC (abst# 3511)

ASCO granted an exception to its abstract policy so that data from this analysis could be released early (17 April) because it shows that patients with certain RAS mutations beyond KRAS may have a negative outcome from treatment with Vectibix. ASCO and Amgen strongly believe oncologists need this information now in order to make informed decisions about choosing effective treatments for their patients.

  • Randomized comparison of FOLFIRI plus cetuximab versus FOLFIRI plus bevacizumab as first-line treatment of KRAS wild-type mCRC: German AIO study KRK-0306 (FIRE-3) (Abst# LBA3506)

Outcome of this trial may determine if patients truly benefit from this class of drugs in the first line setting.

Non-Small Cell Lung Cancer (NSCLC):

    • A randomized study of ganetespib, a heat shock protein 90 inhibitor, in combination with docetaxel versus docetaxel alone for second-line therapy of lung adenocarcinoma (GALAXY-1) (Abst# CRA8007)

This is Synta’s lead product for 2nd line NSCLC. Previous interim results from GALAXY-1 have been positive, which leads us to suspect that this interim analysis will continue in a positive trend.  Final data (PFS/OS) for GALAXY-1 should be ready in time for EMSO2013 in Amsterdam or WCLC2013 in Sydney. The key for ganetespib’s initial success lies in any additional toxicity in combination with docetaxel. Note that GALAXY-2 (Phase III 2nd line NSCLC with docetaxel) has recently began enrolling patients. Clinicians will clearly contrast ganetespib with nintedanib (see below).

    • Nintedanib (BIBF 1120) plus docetaxel in NSCLC patients progressing after first-line chemotherapy: LUME Lung 1, a randomized, double-blind phase III trial. (Abst# LBA8011)

This is Boehringer Ingelheim’s second foray into the NSCLC. Their lead agent, afatinib is currently under regulatory review with both the FDA and EMA. Like ganetespib above, the key issue for nintedanib is toxicity in combination with docetaxel (provided the data is positive).Nintedanib clearly has the early lead when compared to ganetespib for becoming the newest agent in 2nd line NSCLC. Positive data in  LUME Lung-1 would be the second shot in the goal for Boehringer Ingelheim and their NSCLC franchise.

Prostate Cancer (PrCa):

  • Abstract #5016: A randomized phase II study evaluating the optimal sequencing of sipuleucel-T and androgen deprivation therapy (ADT) in biochemically recurrent prostate cancer (BRPC): Immune results (Abst# 5016)

With the increasing number of approved treatments available for prostate cancer the biggest challenge is how to best sequence the drugs to maximize efficacy and minimize toxicity.  Because Provenge does not alter PFS but does improve survival, there has been much discussion regarding the optimal place for its use.  This abstract may offer some guidance or at least improve understanding.

 

    • Abstract #5004: ERG rearrangements and association with clinical outcome in patients (pts) receiving abiraterone acetate (AA) (Abst#5016)

Results from the COU-AA-302 study in chemotherapy (chemo)-naïve metastatic castration-resistant prostate cancer (mCRPC): The increasing number of targeted cancer therapies in development has necessitated the need for biomarkers to aid in determining patients most likely to respond to and benefit from each treatment.  Biomarkers will be increasingly valuable for patients and physicians in the decision making process.   ERG rearrangement in prostate cancer at the time of diagnosis, are markers for predicting subsequent tumor behavior and can help in better predicting the clinical outcome.

Kidney Cancer (RCC):

    • Record-3: Phase II randomized trial comparing sequential first-line everolimus and second-line sunitinib versus first-line sunitinib and second-line everolimus in mRCC (abst# 4504)

Trials evaluating sequencing of targeted therapies are always important in RCC, although mTOR use is uncommon in the first line setting. 

    • Clinical activity, safety, and biomarkers of MPDL3280A, an engineered PD-L1 antibody in mRCC (Abst# 4505)

This is early data, but it will be interesting to see how this agent compares to BMS’ nivolumab (anti-PD1), which is already in Ph III for RCC.

Melanoma:

    • Long-term follow-up data on the safety and efficacy of singe-agent nivolumab (an anti-PD-1 antibody) in patients with advanced melanoma (Abstract #CRA9006)

Nivolumab (BMS) , a new immunomodulator, made a big splash at last year’s ASCO and BMS has lost no time in fleshing out its development program across a number of tumor types.  Since its debut last year companies with other agents like nivolumab have sprung into action, with clinical data presentations for quite a few of them on the schedule.

    • Findings from a Phase III trial exploring the effect of the anti-PD-L1 antibody drug MPDL3280A in patients with locally advanced or metastatic solid tumors (Abstract #3000)

This study of MPDL3280A (Roche) in patients with solid tumors will be presented by Roy Herbst (Yale). It is most unusual for a Phase III trial to include patients with many different tumor types, and we are intrigued by what Roche plans to do with the data (should the study be positive).

    • BRAF inhibitor (BRAFi) dabrafenib in combination with the MEK1/2 inhibitor (MEKi) trametinib in BRAFi-naive and BRAFi-resistant patients (pts) with BRAF mutation-positive metastatic melanoma (MM). (Abst#9005)

Interest is high here for this combination of TKIs from GSK. Phase II data was very promising at last year’s ASCO, and NDA has been filed with the FDA, so any updates will be followed very closely by all stakeholders.

Glioblastoma (GBM):

    • RTOG 0825: Phase III double-blind placebo-controlled trial evaluating bevacizumab in newly diagnosed GBM (Abst# 1)

ASCO’s top abstract. Presentation of results from this trial, along with the previously-reported AVAglio trial, will help determine the benefit of adding Avastin to standard chemo and radiotherapy in newly-diagnosed GBM.

    • Bevacizumab, irinotecan, and radiotherapy versus standard temozolomide and radiotherapy in newly diagnosed, MGMT-nonmethylated GBM: First results from the randomized multicenter GLARIUS trial (Abst# LBA2000)

GBM patients with non-methlyated MGMT are resistant to treatment with the current standard of care chemotherapy (temozolomide), so if Avastin/irinotecan proves useful in this setting, it will be an important option for this group of patients who are currently without effective therapy.

Thyroid Cancer (ThyCa):

    • Sorafenib in locally advanced or metastatic patients with radioactive iodine-refractory differentiated thyroid cancer: The Ph III DECISION trial (Abst# 4)

Another top Abstract at ASCO: Earlier this year, Bayer announced that DECISION met its primary endpoint, so it will be exciting to see just how effective Nexavar is in this difficult setting in thyroid cancer.

    • Phase II study of everolimus and sorafenib for the treatment of metastatic thyroid cancer (6024)

It will be interesting to see if the addition of Afinitor to Nexavar (which is known to be effective in thyroid cancer) will add any additional benefit.

Liver Cancer (HCC):

    • Sorafenib alone versus sorafenib combined with gemcitabine and oxaliplatin (GEMOX) in first-line treatment of advanced HCC: Final analysis of the randomized Ph II GONEXT trial (UNICANCER/FFCD PRODIGE 10 trial) (Abst# 4028)

The GONEXT trial will show if the addition of Nexavar to chemotherapy can improve outcomes in HCC, where chemotherapy alone is not very effective. HCC is a difficult disease, and many patients have difficulty with the side effects of Nexavar alone—this combination will have to overcome the potential for increased toxicity with some significant benefit in survival in order to be successful.

    • Ph II trial of Pexa-Vec (pexastimogene devacirepvec; JX-594), an oncolytic and immunotherapeutic vaccinia virus, followed by sorafenib in patients with advanced HCC (Abst# 4122)

Oncolytic viruses are a novel approach in oncology, particularly in HCC. This Ph II data will hopefully be the first indication of whether Pexa-Vec will be effective and well-tolerated.


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: Oncology, Cancer Drug Development, Drug Development, Breast Cancer, Breast Cancer Drug Development, Breast Cancer Oncology, Kidney Cancer, Liver Cancer, Thyroid Cancer, Glioblastoma, Melanoma, Prostate Cancer, Lung Cancer, Colorectal Cancer, ASCO

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

Molecular Testing in Trouble from Medicare. Who’s on First?

Posted by Judi Space on Tue,Apr 02, 2013 @ 06:00 PM

Only a Bureaucracy as Inefficient and Unwieldy as Medicare Could Create a Mess This Bad and Then Walk Away Whistling, Hands in Pockets

Medicare's decision to stop reimbursing labs for molecular testing threatens both the labs and the patients who badly need these potentially life-saving testsI’m referring to Medicare’s decision to stop paying bills for molecular testing and other diagnostic tests that are transforming the way many life-threatening diseases are being treated.  This is a decision affecting hundreds of labs, including labs performing proprietary tests that target treatments for cancer patients and other serious conditions. To be clear, this is not a decision to permanently stop paying, but to withhold payments until a favorable alternative has been found to the current system of reimbursement.

Could this have come at a worse time, a time at which significant medical and diagnostic gains are being made by molecular testing?

What began as an honest effort to reduce costs has devolved into a quagmire of indecision, with no one taking charge of resolving the mess.  In the meantime, bills from hundreds of labs and health care companies are going unpaid, with no clear resolution in sight. Just how long labs and health care companies will continue to perform these expensive services without being reimbursed is anyone’s guess, but the situation should be causing alarm bell to go off inside Medicare and the Obama administration. 

Here’s How the Medicare Reimbursement System for Molecular Testing Broke Down

First, Medicare, in a much-needed effort to address an abuse-prone billing and reimbursement system, decided to seek an alternative to the billing process known as “code stacking”, a system whereby the costs and reimbursements for diagnostic tests are determined by identifying the codes and associated costs for each step in performing a particular molecular test.  Rather than paying based on the true value of the test, the code stacking system paid for the steps, I.e., the complexity of a test. This of course opened the door to abuse and inconsistency, with some labs identifying and charging for additional steps.

116 New Codes Went Into Effect in 2011, but Medicare Sat Them Out

In order to replace this with a system of paying based on what was being tested form, in 2010 Medicare asked the American Medical Association to create codes for the most critical and common molecular tests. 116 new codes went into effect in 2011, but Medicare decided to wait until 2012 to use the new system, and until then to continue using the old code stacking method until it could set pricing for the new codes.  In the year since, Medicare has done virtually nothing, and (stunningly) has instead decided to have local Medicare carriers assign prices to each of the diagnostic codes! Now, at the last minute, instead of a unified pricing and reimbursement standard, the local Medicare carriers are forced to determine pricing.

Tests Going Unpaid, at Least for Now

As a result, many prices have not been established, and many tests are going unpaid. The market for the development of new tests is being hammered with uncertainty, with many investors sidelined until the pricing issues are resolved. To get by, some contractors are beginning to mirror the pricing charged by the Medicare contractor for California, the only carrier who has managed to set rates. One can question whether a state as large and unique as California should be driving the rates for the US as a whole.  That said, other contractors are not following the California model, and are not getting paid.

On April 30, Medicare contractors are scheduled to submit their 2013 pricing, including their prices for molecular testing. Once this occurs, it is possible that the labs will get paid after the fact. However, this is not guaranteed, and the deadline is not firm.

Is it Fair for Medicare to Delay Payments for Molecular Testing?

One must ask, is it fair for Medicare to refuse to pay for molecular testing simply because they bungled their own deadline for producing a viable reimbursement system? Should the agency be permitted to walk away from the problem by throwing it into the hands of the Medicare contractors, while in the meantime testing labs go unpaid and patients run a growing risk of having to do without potentially life-saving diagnostic testing?

For more information on this timely issue, see the full article that inspired this post on Forbes.


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: Oncology, Targeted Therapy, Molecular Testing

Will Oncology and Pathology Unite on Molecular Testing?

Posted by Judi Space on Wed,Mar 27, 2013 @ 07:00 PM

For more than a decade, we have been listening to the leaders in cancer research tell us that in order for targeted therapy to work, we must be able to identify who will benefit from it through the use of predictive biomarkers. This is the essence of personalized medicine.

Is molecular testing the key to targeted therapies and a solution to a one-size-fits-all approach?Molecular testing (MT) is becoming the new paradigm for determining an individual cancer patient's course of treatment. Although it is fairly widespread in large academic cancer centers, community hospitals and cancer clinics, where most cancer patients are treated, are often completely out of the loop.

Recently the Association of Community Cancer Centers has sought to better understand the scope of this problem through a survey of its members (1). This survey polled the member institutions' administrators, oncologists, pathologists nurses, and pharmacists (N=52 institutions) about policy, practices, and proceedure related to MT as well as reimbursement issues.

Implementing Molecular Testing: Education of Stakeholders is Key

There are many challenges to the implimentation of MT in the community oncology setting(1).  Chief among them is unwillingness of various stakeholders to work together to make MT a routine proceedure for all newly diagnosed cancer patients. The reality is that testing is already being done on a very limited basis for breast cancer patients (HER2, and ER/PR), but the cancer centers appear to balk at the expansion of similar testing in other cancer indications.(2)

It also represents a great new opportunity to improve the coordination between pathologists and oncologists.

In order to implement MT, The ACCC survey indicated that there should be "champions" that drive the institution toward a coordinated testing program. Most often these champions come from the ranks of the oncologists. They must educate their peers and the institution's administration about the necessity for having a MT policy/proceedure to decide how and when specific tests will be implemented.

Will Oncology & Pathology Come Together Over MT?

Can oncology and pathology unite over molecular testing?The lack of collaboration between pathologists and oncologists is one of the things that's holding molecular testing programs back. Many physicians can't seem to agree on whether MT is necessary, and when. Some don't see the value in personalized medicine, while cancer center administrators see it as simply a line in the budget and are unwilling to spend the time and money in an environment of competing interests.

However, there is safety in numbers. By uniting on the molecular testing issue, oncologists and pathologists will have a greater chance of convincing administrators its necessity.

Is Molecular Testing Costly or Cost Effective?

One of the drawbacks to molecular testing programs is the cost of testing. The decision for doing MT may lie with the payer, rather than the patient's specific needs.  Each assay can run as much as $7,000, which can make insurance companies unwilling to cover the cost in many cases.

However, most oncologists and pathologists agree that molecular testing can actually save money in the long run. The detailed, personal information that it provides can guide an otherwise uncertain treatment plan. A negative test result can save a lot of money on expensive, targeted therapies.

In order for progress to take place, continuing education is essential. This is true of both the medical oncologists and the pathologists. In the rapidly evolving world of cancer drug development, new molecular tests will emerge on a regular basis which will help choose new options for treatment where there were none before.  Pathologists and oncologists must work together to use the test results to guide treatment by identifying who will benefit from specific targeted therapy regimens. 

References

(1)http://accc-cancer.org/education/molecularTesting-Overview.asp

(2) http://obroncology.com/obrgreen/article/Molecular-Testing-Preparing-for-the-New-Normal-in-Community-Oncology


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: Oncology, Predictive Biomarkers, Targeted Therapy, Drug Development, Molecular Testing, Personalized Medicine

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

Orphan Diseases Open Opportunity for Pharma, Biotech Drug Developers

Posted by Shannon Flynn on Sat,Feb 23, 2013 @ 09:00 AM

Orphan Diseases Attract Increasing Attention Across the Board

The lack of FDA-approved orphan drugs represents a significant economic opportunity for pharma and biotech drug development firmsAs patents expire and generic competition increases, more drug companies are investing in the development of therapeutics for orphan diseases. Although the pool of patients for an orphan disease is small, the economic potential of an expensive biologic administered over the lifetime of a limited number of patients presents an attractive commercial opportunity that is a savvy alternative to the en mass selling of lower-priced small molecule compounds which are the mainstay of the industry.

Pharma / Biotech Economics: 7,000 Orphan Diseases, 200 Treatments

Thomson Reuters reports that in the U.S. alone, rare diseases afflict an estimated 25 million people, representing approximately 8% of the total population[i]. According to the National Organization for Rare Disorders (NORD) nearly 7,000 orphan diseases have been categorized already and that number continues to grow year by year as new discoveries are made. Nevertheless, only about 200 of these have FDA approved treatments, leaving the market wide-open to newcomers.

In 2011, orphan drugs represented one third of NMEs approved by the FDA. The same year the orphan drug market was estimated at over $50 billion, accounting for roughly 6% of all pharmaceutical sales. In 2012, approximately one quarter of the 39 new drugs approved by the FDA had orphan status. This pattern continues, as a recent analysis reports that nearly 1,800 of the 5,400 drugs currently in development have received orphan status[ii].

In addition to tantalizing premium prices, which can range from $100,000 to over $400,000 per patient annually, growth is driven by government incentives including tax credits, grants, and regulatory fee waivers as well as shortened approval times and higher probability of approval. Faster uptake, lower marketing costs and longer market exclusivity are also key drivers of growth. In addition, patient organizations often raise funds for research, lowering R&D spend.

Hurdles to Drug Development

Though the lucrative profit potential of these drugs is alluring, success in the orphan market is not without its own set of challenges. Lack of education and awareness among patients and providers alike, along with sometimes poor diagnostic methods hinders identification of the target patient population. Rare disorders are often cryptic, leaving patients misdiagnosed or undiagnosed for long periods of time which can span many years. For example, it is not uncommon for patients suffering with Hereditary Angioedema (HAE) to wait up to 10 years before receiving an accurate diagnosis[iii].

Locating and recruiting patients poses logistical problems to organizing and carrying out clinical trials, resulting in increased costs. Nevertheless, companies have proven successful in overcoming these obstacles and expanding the patient population through utilizing social media, engaging patient advocacy groups and spearheading awareness campaigns and educational programs.

While the economic burden of leaving the population untreated typically outweighs the costs of treatment due to improved patient outcomes, as interest in high-priced, specialty drugs continues to grow, so does the potential for payer pushback. At present, the jaw-dropping costs are largely covered by government programs, health plans and company-sponsored payment assistance programs in order to ensure access to affordable care for patients.

Nevertheless, as patient phenotyping and personalized medicine further characterize more common diseases into specific indications, the number of diseases that meet the criteria for orphan status will continue to expand, placing even greater burden on the healthcare system.

Worthwhile Opportunity for Pharma and Biotech Drug Developers for the Foreseeable Future

For the moment however, it appears the benefits of orphan drug development far outweigh the cost for industry and payers alike, creating a stable and growing market ripe with opportunity.

 


[i] “The Economic Power of Orphan Drugs” Thomson Reuters Report, Aug 2012

[ii] “Innovation in the Biopharmaceutical Pipeline: A multi-dimensional view” Analysis Group, Jan 2013

[iii]  Lunn, M. L., C. B. Santos, and T. J. Craig. "Is There a Need for Clinical Guidelines in the United States for the Diagnosis of Hereditary Angioedema and the Screening of Family Members of Affected Patients?" Annals of Allergy Asthma & Immunology 104.3 (2010): 211-14.


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 Development, Pharma Consulting, Biotech Consulting, Orphan Drug Development

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

FDA-Mixed Response to Proposed Faster Drug Development Pathway

Posted by Tom Penrice on Thu,Feb 07, 2013 @ 04:00 PM

Does the US Need Another Expedited Drug Development Pathway?

The FDA’s meeting to discuss a proposed new pathway aimed at expediting the development of “medicines intended to treat serious or life-threatening conditions with unmet medical needs”, met with a mixed response on February 4th.  The proposal was prompted by a report last fall from the US President’s Council of Advisors on Science and Technology(PCAST), which said a “special medical use”(SMU) pathway could improve drug evaluation in the US.

FDA receives mixed results on proposal for faster drug development pathwayThe Public Weighs In

Participants weighing in on the issue included representatives from Cubist Pharmaceuticals, Trius Therapeutics, Biotechnology Industry Organization, The National Research Center for Women & Families, and Antibiotics Working Group (AWG).

Is There a Need for an Alternate Drug Development Pathway?

Creating an alternative approval pathway could "greatly enhance" the prospects for successful clinical development of novel antimicrobials against the ESKAPE pathogens and would complement the GAIN Act's incentives (Generating Antibiotic Incentives Now (GAIN) Act).

However, there are already six other expedited drug development pathways in place and 50% of the medicines approved in 2009 and 2011 were through a priority pathway. Additionally, various other proposals from the anti-infective development community and the Infectious Diseases Society of America (IDSA) are already on the table, with an assortment of names and acronyms, such as "special population limited medical use" (SPLMU) and "limited population antibacterial drugs" (LPAD).

Some Concerns Brought to Light

There were a few concerns expressed during the discussion, including:

  • Could another expedited drug development pathway create potential congressional intervention resulting in added demands on the FDA?
  • If the FDA pursues its new alternative pathway, could the expedited approval pathways in the Food and Drug Administration Safety and Innovation Act, such as the breakthrough therapies designation, get short shrift?

Suggestions to Enhance Potential Advantages:

Suggestions made for enhancing the potential advantages of the proposal included:

  • Adopt a tiered regulatory framework for the new alternative regulatory pathway, which would allow either disease- or pathogen-based label indications, along with labeling that encourages the most appropriate use of the new medicines commensurate with the approved indications.
     
  • Expand the new initiative to include later stage products, and include indications for which there currently is no guidance, such as prosthetic bone and joint infections, osteomyelitis and bacteremia.
     
  • For antibacterials, the FDA's definition of unmet medical need should not only focus on current needs, but also future needs.
     
  • Balance the dual priorities of expediting clinical development through smaller and more targeted studies and use of authorities that promote responsible prescribing for specific sub-populations through appropriate labeling and restrictions of use.
     
  • Provide clarity about mechanisms or processes to expedite the clinical development of limited use products if it is to include postmarket restrictions of use.
     
  • Make any SMU designation available early in drug development so that manufacturer can design appropriate clinical studies for use under the pathway, for example by conducting trials based on only the most severe manifestation of the disease without having to progress through more moderate disease populations first.
     

You Decide

Is there a need for yet another expedited drug development pathway? As mentioned in our prior post, a streamlined clinical trial process for drug development could have significant strategic planning and competitive intelligence implications for pharmaceutical and biotech firms. Please share your thoughts.


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 Development, Competitive Intelligence

FDA to Consider Faster Drug Development via Smaller Clinical Trials

Posted by Tom Penrice on Fri,Feb 01, 2013 @ 12:00 PM

FDA Hearing on Faster Clinical Trial Process

FDA considers faster drug development process. Implications for Pharma and Biotech Drug Development and Competitive Intelligence.In January the FDA announced it will be holding a public hearing on February 4 and 5, 2013 to gather input on what may lead to a faster clinical trial process for drug and biological products development for "serious or life-threatening conditions that would address and unmet medical need". If approved, an expedited drug development process will be permitted for smaller subpopulations of patients with "more serious manifestations" of a condition. Such a process will lead to faster clinical trials vs. typical studies involving a broader group of patients with a wide range of clinical manifestations.

New Labeling Required

Labeling for approved drugs under the proposed process must clearly show that the drug is "narrowly indicated for use in limited, well-defined subpopulations in which the drug's benefits have been shown to outweigh its risks." Labeling requirements may include an appropriate logo to appear on the container.

Obtaining Public Comments

The purpose of the public hearing is to obtain information and comments on the "need for and feasibility of this pathway and its potential advantages and disadvantages".

Other Highlights

The FDA recognizes that the resource-intensive programs required to approve drugs treating a "broad condition with a wide range of clinical manifestations" requires large study populations which can prevent a drugs from becoming available on a timely basis to patients with "important and unmet medical needs".

It is important to explore the benefits and feasibility of a drug development process for smaller sub-populations of patients with serious or life-threatening conditions, including infections caused by antibiotic-resistant bacteria.

The approval of a narrow indication could be broadened if future data demonstrate the effectiveness and safety in treating a "broader condition or patient population".

For further information, go to http://www.gpo.gov/fdsys/pkg/FR-2013-01-15/pdf/2013-00607.pdf

Impact on the Drug Development Industry

If approved, a streamlined clinical trial process for the development of drugs and biological products may have significant implications for pharmaceutical and biotech firms. Strategic planning and competitive intelligence will take on an added dimension. Forward-thinking strategists would do well to thoroughly consider the implications and the potential to gain a competitive advantage should approval be granted for an expedited drug development process.


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 Development, Competitive Intelligence

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