Plaxgen Working to Expand Sales of Statin Test, Explore Lipid Morphology Data


Plaxgen Working to Expand Sales of Statin Test, Explore Lipid Morphology Data

Nov 21, 2017 | Adam Bonislawski

NEW YORK (360Dx) – Diagnostics firm Plaxgen is looking to expand sales of its StatRes test for predicting patient response to statins.

The Fremont, California-based company has been offering the test on an early-access basis through an agreement it signed last year with St. Joseph Health, a regional hospital system with five hospitals throughout Northern California and is now working to expand its reach through similar agreements with additional hospitals, said Shanmugavel Madasamy, Plaxgen’s founder and CEO.

The company is also investigating whether data on the morphology of cholesterol particles could help identify patients at risk of cardiac events and guide statin therapy. In September, company researchers and their collaborators published a study in the Journal of Visualized Experiments in which they found links between particle morphology and abnormal lipid levels, and observed changes in patient particle morphology following treatment with various statins.

Launched by Madasamy in 2007, Plaxgen uses a system that combines the capture of target biomarkers on plaque arrays with the isolation and analysis of those markers by techniques including flow cytometry and MALDI mass spectrometry.

The company’s plaque array system works essentially as an enrichment step, allowing researchers to investigate only plaque-related serum proteins, as opposed to the full serum proteome. The arrays are composed of soluble plaque-forming constituents that are then incubated with serum from test subjects. These plaque-forming constituents work as substrates for the plaque-related serum analytes, allowing for their pull-down and subsequent analysis.

Last year, the company published a paper on the StatRes test in the American Journal of Cardiology looking at 30 serum samples from patients with high cholesterol who went on to receive treatment with statins. It found that it was able to predict response in 13 of 15 patients receiving simvastatin and 12 of 15 patients on atorvastatin.

The company is now putting together a larger clinical validation trial in which it plans to follow thousands of patients over the course of four years. Madasamy said it hopes with that data to take the test through the US Food and Drug Administration regulatory process. Plaxgen currently offers the StatRes test as a laboratory-developed test through its CLIA lab.

In the JoVE study, the company paired its plaque capture system with analysis by imaging flow cytometry, which allowed it to study the shape of circulating cholesterol particles.

“In general, it’s understood that in atherosclerosis, not only the number of particles, but also the morphology and size of the particles, plays an important role [in the condition],” Madasamy said. However, he noted, the role of morphology has seen relatively little study compared to work focused on quantification of lipids involved in atherosclerosis.

The researchers used Plaxgen’s technology coupled to imaging flow cytometry to compare the morphology of cholesterol particles in 50 patients with plaque disease and age-matched healthy controls, and found that the subjects with plaque disease had higher levels of linear-shaped particles (mean of 18.3 percent) compared to healthy controls (mean of 11.1 percent).

They also used the platform to look at the changes in morphology of cholesterol particles in response to treatment with various lipid-lowering agents, incubating isolated particles with lovastatin, simvastatin, atorvastatin, rosuvastatin, fluvastatin, ezetimibe, fibrate, niacin, and omega-3 fatty acid. They analyzed drug-induced morphology changes and found that lovastatin, simvastatin, atorvastatin, and ezetimibe induced the formation of both linear and globular morphologies, while rosuvastatin, fluvastatin, fibrate, niacin, and omega-3 fatty acid induced formation of only globular particles.

The results, Madasamy said, suggest both the role of morphology in plaque disease and that different lipid-lowering drugs may have different effects on this morphology.

“We believe that in specific populations, the morphology data could be a biomarker to complement [existing] diagnostics to improve accuracy,” he said. “Because, yes, a patient’s lipid levels can look fine, but they can still have a heart attack or stroke.”

Madasamy said Plaxgen is now applying its morphology analysis to the amyloid-beta plaques characteristic of Alzheimer’s disease, another area of focus for the company.

“We are expanding to that and have data that we hope to publish next year,” he said.






Scrip Asks… What’s The Current Climate For Deal-Making? (Part 1)

Scrip Asks… What’s The Current Climate For Deal-Making? (Part 1)

  • 16 Oct 2017

Joseph Haas

Executive Summary

Following Gilead’s acquisition of Kite, buzz grew that the deal might catalyze a surge in deal-making. Scrip asked a broad cross-section of biopharma insiders and observers about the deal-making environment – first up are responses from small biotechs.

Gilead Sciences Inc.‘s recent buy-out of Kite Pharma Inc. for $11.9bn to super-charge its cancer pipeline ended a long period of speculation about what Gilead would do with its stockpile of cash – and set off a new round of speculation about the state of the deal-making environment across the biopharma industry.

What’s Gilead Getting From Kite For Nearly $12bn?

By Mandy Jackson 29 Aug 2017

The $180 per share that Gilead’s paying for CAR-T maker Kite was deemed too high by some and just right by others, but the big biotech expects a lot from its new cell therapy platform.

Read the full article here

Scrip asked a cross-section of people in the industry – from large and small companies, market analysts and other industry observers – what they make of the current climate for deal-making. Here, in their own words, are the responses from the biotech sector, defined here as smaller, clinical-stage firms. Part two will provide the responses from big pharma and other respondents.

Having Their Say:

Biotech: Epizyme Inc., Erytech Pharma SA, Kura Oncology Inc., Zavante Therapeutics Inc., CytomX Therapeutics Inc., Fortress Biotech Inc., CANbridge Life Sciences Ltd., Athersys Inc., Corbus Pharmaceuticals Holdings Inc.

Susan Graf, Chief Business Officer, Epizyme

Susan Graf

The current deal-making environment is a positive one-two punch for biopharma. First, today’s equity climate is fueling biopharma companies in their work to discover and develop innovative therapies. Second, big pharma companies continue to need promising new assets to fill their pipelines.

This exciting combination creates a variety of options for biopharma companies as they consider the best way to add more value to their companies, while continuing to do what they do best: innovating new medicines, particularly in areas of large unmet patient need.

Jean-Sebastien Cleiftie, Chief Business Officer, Erytech

Jean-Sebastien Cleiftie

Our perspective on the current climate: although not at the level of 2015, 2017 year-to-date biotech deal-making levels have been robust, especially when we look at licensing in oncology, immuno-oncology and immunology, which will continue to drive transaction activity.

Biotech M&A levels have been contained through the summer, although one transaction can have a dramatic effect on deal statistics, as shown by the recent acquisition of Kite Pharma by Gilead. Furthermore, Q4 is generally an active quarter for deal making, so all in all it is too early to predict what 2017 will look like on the M&A front.

Troy Wilson, CEO, Kura Oncology

Troy Wilson

Although uncertainty around tax reform and drug pricing remains, we continue to see a constructive deal-making environment for biopharma. Companies and investors continue to seek deal premiums, and buyers appear to be exercising discipline. Large pharma are willing to pay a premium when products have been significantly de-risked while smaller companies must compete aggressively as they look to challenge the incumbents.

As a result, we are seeing companies such as Incyte Corp., Tesaro Inc., Clovis Oncology Inc. and others begin to expand their scope and become strategic partners in their own right. In general, it makes for a pretty healthy biopharma ecosystem.

“This feels more like a slowdown as [big pharma] integrate their previous acquisitions and they assess what is going to happen with pricing and reimbursement.” – Zavante’s Schroeder

Ted Schroeder, President and CEO, Zavante Therapeutics

Ted Schroeder

I would characterize the current deal climate as active, but cautious. I find the current situation interesting for two reasons 1) Money is still relatively cheap and 2) Most companies remain under-valued. While I don’t have great insight into the minds of big pharma, this feels more like a slowdown as they integrate their previous acquisitions and they assess what is going to happen with pricing and reimbursement.

Allergan PLC’s shift to deals that are accretive in the short term (e.g. aesthetics) likely gives the rest of the players the sense that they don’t have to be quite so aggressive for therapeutic deals. (Also see “Allergan Adds Accretive Aesthetics Assets In $2.9bn LifeCell Acquisition” – Scrip, 21 Dec, 2016.) Novel oncology assets still seem to be in high demand. Big pharma and biotech still need to fill their pipelines so I expect a steady deal flow going forward, but perhaps not quite like 2016.

Debanjan Ray, CFO and Head of Corporate Development, CytomX

Debanjan Ray

We find the current biopharma deal-making environment to be strong. Our recent interactions with pharma suggest that these companies value innovation, and are willing to think creatively to access innovative programs and platforms that have the potential to make a difference for patients.

In the past 18 months, we’ve closed collaborations with AbbVie Inc., Bristol-Myers Squibb Co.and Amgen Inc. In these collaborations, our partners have been willing to structure deals that bring value to CytomX in the near term and the long term – for example, retention of certain development responsibilities and profit splits on certain products. This sort of creativity in deal structuring is highly valued by biotech companies such as CytomX, and tend to result in more productive collaboration discussions between biotech and pharma.

Lindsay Rosenwald, CEO, Fortress Biotech

Lindsay Rosenwald

I think the climate is as good as it’s ever been. There’s a great feel of demand for novel drug therapies in big pharma, big biotech, specialty pharma and even mid-sized and smaller companies so it all looks good right now. Which is always scary, right?

When I go to conferences, they’re very crowded with lots of inquiries, lots of interest and it’s like a bazaar, there’s so many people interested in so many different programs. If you look at the announcements of all the deals, it seems there’s a good volume of them.

From my perspective, because we’re involved in lots of different technologies, lots of different companies, there is certainly a lot of interest from all parts of the industry and it seems like the demand for novel agents addressing unmet medical needs – I’ve never seen the demand as great as it is right now.

“Capital market access for follow-on offerings has become somewhat more challenging since the peaking of sector performance in 2015. We believe this creates a very favorable environment for deal-making, as companies look to identify alternative funding sources.” – CANbridge’s Xue

James Xue, Founder, Chairman and CEO, CANbridge Life Sciences

James Xue

We are very optimistic about the current deal-making environment in the biopharma industry, which has seen historic inflows of capital over the last five years and a record number of IPOs. With that influx of capital, exciting new therapeutic candidates have received much needed initial funding to support their advancement. However, capital market access for follow-on offerings has become somewhat more challenging since the peaking of sector performance in 2015. We believe this creates a very favorable environment for deal-making, as companies look to identify alternative funding sources.

Our particular model is to identify validated Western drug candidates for development and commercialization in China and northern Asia. In this sector, we are observing a rise in cross-border transactions between Western and Chinese companies, such as the recently announced agreement between Celgene Corp. and BeiGene (Beijing) Co. Ltd. (Also see “Celgene Eyes IO Growth With BeiGene China Pact” – Scrip, 6 Jul, 2017.) These types of deals can allow companies access to markets not otherwise easily accessed, as well as additional non-dilutive capital, which we believe will continue to make them attractive and a growing component of the environment.

Gil Van Bokkelen, CEO, Athersys

Gil Van Bokkelen

There is substantial interest in technologies that have the potential to address areas of significant unmet medical need, and we believe that will continue to be the case. This is especially true for innovative technologies targeted at indications that are related to the unprecedented demographic transition now occurring, with the large increase in the number of people age 65 and older as the baby boom generation gets older. This will have a massive global impact on health care, since there are quite a few diseases and conditions that will become more prevalent as the global population ages.

Unfortunately, many of these conditions currently lack effective treatment solutions, and for the patients that may mean institutional care, family care or professional home health care, and most families and societies around the world are simply unprepared for that. That need creates opportunities for innovative companies developing safer and more effective treatment solutions that can help improve quality of life for patients.

“We’ve been hearing from big pharma … that there is real concern over high valuations of late-stage public companies that could be targets.” – Corbus’ Cohen

Yuval Cohen, CEO, Corbus

Yuval Cohen

There has been a real drought in deals this year and so the recent Gilead/Kite deal was a very welcome change in that. It is probably too soon to see whether that was the start of a change or a one-off. What we’ve been hearing from big pharma is that there is real concern over high valuations of late-stage public companies that could be targets, but that is always counteracted by the ever-present need of big pharma for novel promising drugs in their pipelines. My feeling is that we will see a return to robust M&A activity shortly but perhaps more on the earlier (hence less expensive) side.


Heat Biologics shifts focus from HS- 110/cyclophosphamide to Opdivo combo in NSCLC- exec; potential to boost PD-1 inhibitor response rate- oncologists

Low TIL responses could mean Opdivo nonresponder conversions

Possible additional combination trial arms in future

Minimal side effects attractive for combination therapy

Heat Biologics (NASDAQ:HTBX) is no longer actively pursuing its Phase II drug combination trial of HS-110 (viagenpumatucel-L) with cyclophosphamide in non-small-cell lung cancer (NSCLC), said CSO Taylor Schreiber.

The ongoing trial (NCT02117024), due to report data in 4Q16, was designed for latter lines of therapy when Bristol-Myers Squibb’s (NYSE:BMY) Opdivo (nivolumab) was not available, he said. However, since Opdivo’s approval last year, it has become standard of care in secondline NSCLC, he noted. Rather, the company focus is on the 100-patient Phase Ib/II combination DURGA trial (NCT02439450) of HS-110 with Opdivo in NSCLC, he said.

The company has indicated that it will release some data from the DURGA trial in 4Q16, whilst this news service reported 20 September that data from the trial had been submitted to the World Conference on Lung Cancer in December. The Phase Ib primary outcome measure is safety and tolerability whilst the Phase II primary outcome measure is to evaluate the objective response rate (ORR). The trial has a listed primary completion date of March 2018, according to

The company had to stop enrolling for the DURGA trial in the first part of 2016 given financial constraints, said Schreiber. However, it has now reopened for enrollment and one additional patient has been recruited, he said but did not comment further on patient numbers or finances.

Schreiber also noted the DURGA trial has a flexible design and the company may add additional combination arms to the trial at a later date. Costimulatory molecules, such as OX40, and other immune checkpoints could be of interest, he added.

Potential Opdivo synergies

Whilst highly efficacious in some patients, PD-1/checkpoint inhibitors like Opdivo only appear to derive benefit in approximately 20% of unselected NSCLC patients, oncologists said.  Improving responses to Opdivo with HS-110’s mechanism of action could provide a useful way to boost responses, they noted.

HS-110 works on a different pathway of the immune system compared with the checkpoint inhibitors, said Dr Wael Harb, founder, Horizon Oncology Center, Lafayette, Indiana and Dr Daniel Morgensztern, associate professor, Washington University School of Medicine, St Louis, Missouri, both investigators in the ongoing HS-110/Opdivo trial. The combination may harness this pathway in order to attack a subset of tumours that do not normally respond to Opdivo, they said.

Two patients thus far have had durable responses and one of those was heavily pretreated with several lines of treatment, said Harb. Typically, this type of patient would not be expected to have a good response to any therapy at this stage, he added. The duration of response has also been well beyond the timelines that would be predicted for single-agent Opdivo, said Harb. This remains to be tested in a wider population, but the early data from patients could suggest the vaccine is helping to activate the immune system against the tumour cells, Harb added.

The DURGA trial is investigating patients two subgroups, patients with high tumour infiltrating lymphocytes (TILs) and patients with low TILs, according to In order to have responses to PD1 antibodies such as Opdivo, TILs are necessary, said Morgensztern. Both of the aforementioned patients had low TILs that one would typically not be expected to respond well to checkpoint inhibitors, Harb said. Approximately 50% of NSCLC tumours are for patients with low TIL counts around the tumour, said Schreiber.  The hope is that HS-110 will cause a Tcell response to the tumour in patients with low TIL at baseline and convert them into responders to Opdivo, he explained.

HS-110 differs from other vaccines in that it delivers tumour antigens in order to generate a CD8 positive T-cell immune-mediated response, said Schreiber. Most other vaccine approaches depend upon complexing of a single antigen or a small number of antigens and do not generate a CD-8 positive T-cell response, he explained. There is clinical data demonstrating that the strongest predictor of patients who respond to PD-1 or CTLA4 inhibitors is the magnitude of CD8 positive T-cell response in a tumour biopsy, said Schreiber. The future in immuno-oncology belongs to combination therapies, said Morgensztern. There isnot much more to be done with single agent PD-1 inhibitors and although work may improve upon the prediction of responders it does not help the nonresponsive patients, he explained.

The crucial treatment goal in immuno-oncology now is increasing the number of patients that do respond to checkpoint inhibitors, he and Harb agreed. BMS’ Yervoy (ipilimumab) or AstraZeneca’s (LON:AZN) tremelimumab, both CTLA4 inhibitors, can be used to improve responses to PD-1 inhibitors, however, this comes with the burden of additional toxicity, said Morgensztern.

Thus far there have been no new side effects or exacerbation of Opdivo side effects, such as autoimmune reactions, with HS-110- treated patients, said Schreiber. The most relevant side effects are injection site reactions and a broader systemic dermal reaction though neither were dose-limiting, he added. Harb noted HS-110 is attractive for a combination therapy, given that patients treated thus far had not had any significant adverse reactions and that HS-110 appeared to be extremely well-tolerated. With other vaccines sometimes patients have flu-like symptoms and cytokine reactions, however, this has been seen minimally with HS-110, he added.

Heat Biologics’ market cap is USD 26m.

by Hamish McDougall in London

Study of Potential Therapy for Congenital Muscular Dystrophy Gets Boost from FDA

msnewstodayStudy of Potential Therapy for Congenital Muscular Dystrophy Gets Boost from FDA

August 31, 2016

By Carolina Henriques

Santhera Pharmaceuticals announced that it has received a $246,000 grant from the U.S. Food and Drug Administration (FDA) to support its ongoing Phase 1 clinical trial evaluating omigapil as a potential treatment for children and adolescents with congenital muscular dystrophy (CMD).

The study, called CALLISTO (NCT01805024), is assessing the pharmacokinetics, safety, and tolerability of omigapil in ambulatory and non-ambulatory children, ages 5–16, with either of two CMD subtypes (COL6-RD or LAMA2-RD). About 20 eligible patients are currently being recruited; more information is available on the study’s clinical website.

“We are delighted that the FDA has awarded us this prestigious and highly competitive grant in support of our CALLISTO trial in CMD,” Thomas Meier, Ph.D., chief executive officer of Santhera, said in a press release. “With this award the FDA emphasizes the need for a therapy for CMD and the contribution of the CALLISTO trial to the development of an effective treatment.”

Severe forms of CMD can cause life-threatening progressive muscle weakness, known as floppy infant syndrome. A contributing factor for disease progression is apoptosis, or cell death, through a cascade of cellular events involving the glyceraldehyde-3-phosphate dehydrogenase (GAPDH) pathways for the transcription of pro-apoptotic genes.

CMD is a clinically distinct group of inherited neuromuscular diseases that manifests with an early onset of symptoms that include weakness, contractures, elevated creatine kinase levels, an inability to stand or walk, eating difficulties, and respiratory insufficiency.

Omigapil is a deprenyl-analog with anti-apoptotic properties that binds to GAPDH. This interaction leads to its inhibition, and is thought to underlie the compound’s observed anti-apoptotic effect. In animal models of CMD, omigapil was seen to prevent cell death, reduce body weight loss and skeletal deformation, and to improve locomotive activity.

The proposed treatment was given Fast Track designation by the FDA for the treatment of CMD in May, and has previously been granted Orphan Drug Designation for the same indication in Europe and the United States. Santhera’s grant award came from the FEA’s Office of Orphan Products Development.

“As the leading organization representing the interests of patients with CMD, we are very pleased that the FDA recognizes the need to advance medical research in this orphan disease. With currently no effective treatment available for patients, the CALLISTO trial offers hope to patients with this devastating disease,” said Patrick May, CureCMD’s president.

The trial is being conducted in collaboration with the U.S. National Institutes of Health (NIH) under the leadership of Professor Carsten Bönnemann and Dr. Reghan Foley, with the National Institute of Neurological Disorders and Stroke (NINDS). Study completion is expected in early 2017.

Omigapil was developed by Novartis, and Santhera holds an exclusive worldwide license for its development as a treatment for congenital muscular dystrophy.

Blood Test for Colorectal Cancer: The Last Resort?


Blood Test for Colorectal Cancer: The Last Resort?

Roxanne Nelson, BSN, RN

August 31, 2016

Despite recommendations, many Americans in the target age group are not getting screened for colorectal cancer.

However, a new blood-based screening test may help boost those rates because of its simplicity and convenience for the patient.

The downside is that the new test is not as sensitive or accurate as a colonoscopy or the other recommended screening approaches.

Approved in April 2016, the Epi proColon (Epigenomics AG) is the first blood-based colorectal screening test to get a thumbs-up from the US Food and Drug Administration (FDA).

This molecular test detects methylated Septin 9 DNA in plasma, which is increased in colorectal cancer and can be found in tumor DNA that has been shed into the bloodstream from both colon and rectal sites. This makes it a differential biomarker for the early detection of colorectal cancer, according to the manufacturer.

Available in Europe since 2012, it is also being marketed in other countries, including China.

The question now facing healthcare providers is, Where does this new test fit in the current armamentarium of screening options?

“It’s the new kid on the block, another alternative, and one that isn’t as highly recommended as the current options that are available,” said Andrew Chan, MD, an associate professor of medicine at Harvard Medical School and a practicing gastroenterologist at Massachusetts General Hospital in Boston.

The major advantage of the Epi proColon is that because it is fast, easy, and noninvasive, it may appeal to individuals who have shunned other screening approaches.

“I believe that any screening test is better than no screening,” Dr Chan told Medscape Medical News. “But we also have to be cautious about using screening tests simply because they are easy to employ. Screening also involves a follow-up and a discussion of the results.”

What isn’t clear is whether the benefits outweigh the risks, he explained. “Or if there are tradeoffs, such as the test picking up false-positives or the consequence of false-negatives, which may give the patient an inappropriate sense of security.”

Basically, there are a lot of caveats with this test, and it shouldn’t be considered an easy alternative. “This blood test hasn’t been shown to reduce mortality from colon cancer, which is the most important data,” Dr Chan emphasized. “So we don’t know how it is going to compare to the other established screening tests.”

Need for More Options

Both the incidence of and mortality from colorectal cancer have been declining in recent years, and much of that is attributed to screening.

However, screening rates are well below the targets designated by public health agencies. According to National Health Interview Survey data, screening use overall was below the targets; there were no improvements from 2010 to 2013 for not only colorectal cancer screening but also for breast and cervical cancer.

But for colorectal cancer screening, after adjustments were made for age, 58.2% of survey respondents aged 50 to 75 years reported getting screened.

This rate falls short of the Healthy People 2020 target of 70.5% (2008 baseline, 52.1%). In addition, screening was lower among Asians and all Hispanic subgroups except Puerto Ricans, and younger individuals were less likely to be screened (50 to 64 years, 52.8%) compared with older persons (age 65 to 75 years, 69.4%).

“Anything that brings more people into screening is great,” commented David Johnson, MD, a past president of the American College of Gastroenterology (ACG) and coauthor of the ACG’s colorectal cancer screening guideline. But this new blood test “is not meant to replace any of the better tests that are available now, and that is the undercurrent message.”

The Epi proColon is primarily meant for people who have declined other types of screening, he told Medscape Medical News. “This is a test that only detects cancer, and the best test should be able to prevent cancer, and recognize precancerous polyps.”

The ultimate screening test should mitigate toward cancer prevention rather than detection, explained Dr Johnson, who is also professor of medicine and chief of gastroenterology at Eastern Virginia School of Medicine, Norfolk.

Colonoscopy has been proven to decrease the incidence of colon cancer and prevent colon cancer-related death, and it remains the preferred strategy in the ACG’s guidelines, last published in 2009, he noted.

“It is the best test is to prevent cancer because it can detect polyps and in turn decreases mortality and colon cancer incidence,” he said. “For every 1% in adenoma detection rate, there was a 3% reduction in the incidence in colon cancer and a 4% reduction in death, and it comes down to polyp removal.”

All of this needs to be put into context in primary care, where most patients will most likely be counseled about screening. “In primary care, when patients ask about the Epi proColon, it should be put into context as to how it compares with other tests,” he said. “And importantly, that the test is just for cancer detection and will not detect precancerous polyps.”

The Centers for Disease Control and Prevention, in conjunction with other groups, has set a goal for a screening rate of 80% by 2018 in order to reduce colon cancer incidence and death rates.

“This test could help reach that goal,” Dr Johnson said. “But only if the patient has been appropriately counseled and refuses everything else, then this becomes an option. It is paramount that the provider puts it into perspective.”

Task Force Guidelines

In their updated 2016 guidelines, the US Preventive Services Task Force (USPSTF) found convincing evidence that colorectal cancer screening substantially reduces disease-related mortality, but it did not recommend any one screening approach over any other.

The USPSTF now recommends seven different screening strategies: colonoscopy, fecal immunochemical testing (FIT) for occult blood, guaiac-based fecal occult blood testing, sigmoidoscopy alone, sigmoidoscopy plus FIT, the FIT-DNA test, and computed tomographic colonography.

They all have varying levels of evidence supporting their effectiveness, and the potential harms also differ among the specific approaches.

Douglas Owens, MD, former Task Force member, general internist at the Veterans Affairs Palo Alto Health Care System, and professor at Stanford University in California, pointed out that the Epi ProColon test was included in the Task Force’s review.

“This screening method currently has limited published evidence evaluating its use,” he said. “It had a sensitivity to detect colorectal cancer of under 50%, which is quite low, as we would want sensitivity levels at about 90% or higher. Therefore, it was not included in the table on screening strategies in the final recommendation statement.”

Dr Owens emphasized that the FDA recommends that the blood test to detect methylated SEPT9 DNA be offered only to patients who have a history of not completing colorectal cancer screening.

“The FDA also recommends that the available tests included in the Task Force’s 2008 final recommendation be offered first,” he said. “The Task Force bases all of its recommendations on the best evidence that is currently available. As such, the tests with sufficient evidence were listed in the table.”

Efficacy of the Test

Two years before the FDA approved the blood test, the Molecular and Clinical Genetics Panel of the FDA’s Medical Devices Advisory Committee reviewed the data. Even though the reception was not overly enthusiastic, they voted by a narrow margin to recommend premarket approval for the test.

Most of the panel agreed that the test was safe (yes, 9; abstain, 1).

But when it came to effectiveness, the panel was decidedly mixed (yes, 5; no, 6), as well as regarding whether its benefits outweigh its risks (yes, 5; no, 4; abstain, 1).

Data from two clinical studies were used in the decision making process.

The first study compared the efficacy of Epi proColon to colonoscopy in 1544 samples drawn from individuals aged 50 to 85 years who were at average risk for colorectal cancer.

The sensitivity of Epi proColon was 68.2% (95% confidence interval [CI], 53% – 80%) and specificity was 80% (95% CI, 77.9% – 82.1%). The negative predictive value was 99.7% (95% CI, 99.6% – 99.8%) and positive predictive value was 2.4% (95% CI, 2% – 3%).

The second study compared the accuracy of Epi proColon to FIT using matched blood and stool samples from 290 participants. Epi proColon was statistically noninferior to FIT with respect to sensitivity (72.2% for Epi proColon vs 68% for FIT) but not specificity (80.8% vs 97.4%).

The manufacturer does agree that the Epi proColon test is not meant to be a simple alternative to the other screening strategies — at least not at this time.

Instead, the company emphasizes that the test is indicated for people who are at average risk for colorectal cancer, are age 50 years and older, and have been offered and have a history of not completing screening by tests recommended in the 2008 USPSTF guidelines.

These recommended tests should be offered and declined before Epi proColon is offered as an option for screening, and specifically, the Epi proColon is not intended to replace screening tests recommended by appropriate guidelines, the company emphasizes.

“There are 23 million average risk people who are not getting screened,” said Noel Doheny, CEO of Epigenomics USA. “And those are the people we are targeting.”

The assumption was that people who were unwilling or unable to undergo screening with the recommended tests might do so if an easier option was available. “The third study we did is pending publication, and it answered the question for the FDA — would somebody who is noncompliant use a blood test,” he explained. “We recruited 413 patients who were twice noncompliant after being told by a physician to get either a colonoscopy or FIT, and 99.5% of those randomized to our test got a blood test on the spot.”

Of 203 individuals in the Epi proColon group, 202 had the test done. Of that group, 30 had a positive test result; of those, 17 individuals went on to have a colonoscopy, with 10 having a polyp removed.

In the FIT group, of the 210 participants who were offered the stool test, 185 completed it (88.1%). There were 3 positive results, and 1 person had a colonoscopy with a polyp removed.

“Participation is the key,” said Doheny. “If you can’t get someone tested, the specificity and sensitivity aren’t of any value. But by getting 99.5% tested, you can now answer those questions for those who were previously noncompliant.”

These are the only data available right now, but he explained that his company is currently in a dialog with the FDA about postapproval studies.

“We are planning trials that will confirm the adherence number and look at the test’s usage over a number of years,” he said.

In addition, there are also trials in place with high-risk patients, and a similar trial in lung cancer has been initiated.

Regarding insurance coverage, Doheny pointed out that the Epi proColon test was actually available for several years before its FDA approval.

“The test was developed over 4 years ago with the help of Quest Diagnostics and ARUP [Associated Regional and University Pathologists] as a laboratory developed test,” he said. “They configured it and offered it, and over the years, a majority of payers have been paying for it.”

“Since we received approval, the number of payers is now likely to be even higher,” Doheny added.

The test still has yet to be approved for insurance reimbursement by the Centers for Medicare & Medicaid Services (CMS), but the company is currently in discussions with CMS.

Dr Johnson disclosed that he has served as a director, officer, partner, employee, advisor, consultant, or trustee for Pfizer Inc, Epigenomics, WebMD, CRH Medical, and Medtronic and has received income in an amount equal to or greater than $250 from Pfizer Inc, Epigenomics, WebMD, CRH Medical, and Medtronic. Dr Chan reports consulting for Bayer Healthcare, Pfizer Inc, and Pozen Inc.

Follow Medscape Oncology on Twitter: @MedscapeOnc


Medscape Medical News © 2016  WebMD, LLC

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Cite this article: Blood Test for Colorectal C

Duchenne muscular dystrophy drugs at the crossroads, as newer agents advance

VOLUME 34 NUMBER 7 JULY 2016 p675

The first generation of exon-skipping drugs for Duchenne muscular dystrophy (DMD) has reached a critical juncture, as an FDA decision on whether to grant accelerated approval to Sarepta Therapeutics’ controversial drug Exondys (eteplirsen) looms. A rival effort at BioMarin Pharmaceutical, of San Rafael, California, is now over. Biomarin withdrew a European application for Kyndrisa (drisapersen) on May 31, after unsuccessful talks with European Medicines Agency officials, and the US Food and Drug Administration (FDA) refused to approve the same drug in January.

The refusals were unequivocal—drisapersen was neither safe nor effective. In the case of Sarepta’s eteplirsen, however, regulatory uncertainty abounds. The Cambridge, Massachusetts–based biotech, is seeking approval with evidence from just 12 patients. “In any other therapeutic area, the agency would be within its rights to
say this data set is very exciting—come back when you’ve conducted a trial which proves it’s safe and effective,” says Glyn Edwards, CEO of Abingdon, UK–based Summit Therapeutics.

“The normal balance of evidence hasn’t been achieved for this drug yet.”

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Task Force Grants Broad Support For Colorectal Cancer Screening Tools


Task Force Grants Broad Support For Colorectal Cancer Screening Tools

By David Filmore
Around The Industry

June 16 2016 6:00 PM

Executive Summary

The US Preventive Services Task Force said colorectal cancer screening is effective for those aged 50 to 75. It recognizes the potential for a range of methods, from standard colonoscopy to CT colonography, to blood and fecal DNA testing, to be used to increase screening rates. The recommendations could help drive coverage and adoption for several firms’ products.

The federal task force that serves as the primary arbiter of what screening tests should be performed by providers and covered by insurers gave a broad-based thumbs-up to various modes of colorectal screening.

The US Preventive Services Task Force on June 16 granted its strongest “A”-rated recommendation to routine colorectal cancer screening for everyone aged 50 to 75, remaining essentially neutral on the type of test used to perform the screening. While USPSTF’s prior 2008 policy specifically recommended colonoscopy, fecal immunochemical tests, fecal occult blood tests (FOBTs) and flexible sigmoidoscopy (combined with FOBTs), the new policy has a broader reach.

“Instead of emphasizing specific screening approaches, the USPSTF has instead chosen to highlight that there is convincing evidence that colorectal cancer screening substantially reduces deaths from the disease among adults aged 50 to 75 years, and that not enough adults in the United States are using this effective preventive intervention,” the task force said in its recommendations, posted on its website and in the Journal of the American Medical Association.

The USPSTF says it “acknowledges that there is no ‘one-size-fits-all’ approach to colorectal cancer screening, and seeks to provide clinicians and patients with the best possible evidence about the various screening methods.”

This approach could be a boon for several colorectal-cancer screening alternatives, including new fecal and blood DNA tests, and computed tomography (CT) colonography.

In particular, the USPSTF recommendations mention each of these options, including DNA-based fecal testing, offered by Exact Sciences Corp.‘s Cologuard and FDA-approved in 2014, and the first blood-based test approved for colorectal cancer screening, Epigenomics AG‘s Epi proColon SEPT9 DNA assay, approved earlier this year. (See “Epigenomics’ Epi proColon Blood Test Finally Makes The Grade With FDA” — “The Gray Sheet,” Apr. 13, 2016.)

Under federal regulation, private payers participating in insurance exchanges are required to cover services rated as “A” and “B” by USPSTF without cost-sharing. Medicare is not required to cover these services, but if decides to do so, it must cover “A”- or “B”-rated services without co-pays.

In addition to providing an “A” recommendation for screening individuals who are 50 to 75 years old, USPSTF also gave a “C” grade for screening of 76-85 year-olds, saying it should be an individual decision for that population.

USPSTF: No ‘One-Size-Fits-All’ Approach

The task force does not suggest all the screening methods are equal. It specifically details the benefits and harms of each, for instance, noting that evidence for CT colonography is limited to studies of its “test characteristics,” and that it comes with risks of over-diagnosis.

“The USPSTF acknowledges that there is no ‘one-size-fits-all’ approach to colorectal cancer screening and seeks to provide clinicians and patients with the best possible evidence about the various screening methods to enable informed, individual decision-making,” the recommendation states.

While the USPSTF recommendation does not guarantee Medicare coverage, it could make it more likely that CMS will reconsider its coverage policies for various colorectal cancer screening tests. The Medical Imaging & Technology Alliance says that is exactly what it would like to see happen.

For example, CT colonography potentially offers a less-invasive alternative to standard colonoscopy, but has struggled under a national Medicare non-coverage policy established in 2009. (See “Medicare Denies Coverage Of CT Colonography For Cancer Screening” — “The Gray Sheet,” May 18, 2009.)

“We hope this will encourage the Centers for Medicare & Medicaid Services to provide national coverage of CT colonography, granting more beneficiaries access to early detection and lifesaving treatment, and saving millions of lives,” said Patrick Hope, MITA’s executive director.

Epi proColon is also not yet covered by Medicare. The test, which was approved by FDA in the middle of USPSTF’s review, just qualified for inclusion in the recommendation report, according to USPSTF. “A single test characteristic study met the inclusion criteria for the systematic evidence review supporting this recommendation statement; it found the SEPT9 DNA test to have low sensitivity (48%) for detecting colorectal cancer.

The firm says it expects the inclusion of the test in the report to expand adoption and coverage for the assay.

Epigenomics says the new recommendations recognize “the potential role of our novel blood-based test in colorectal cancer screening, especially in driving patient compliance in individuals who are reluctant to collect stool samples or undergo colonoscopy.”

“We continue to work multiple paths for CMS coverage,” Noel Doheny, CEO of Epigenomics’ US subsidiary, told The Gray Sheet.

Cologuard, meanwhile, is already covered by Medicare. But Exact Sciences CEO Kevin Conroy says the company is “pleased with the clarity of these recommendations and expect they will expand and promote utilization of Cologuard as an innovative colon cancer screening option.”

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