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 ClinicalTrials.gov.

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 ClinicalTrials.gov. 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 trials.gov 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

Send comments and news tips to news@medscape.net.

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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Task force removes all ambiguity, doubt from final CRC guidelines

MedicalDeviceDailyTHURSDAY, JUNE 16, 2016                                                                        VOLUME 20, NO. 116


Task force removes all ambiguity, doubt from final CRC guidelines

By Amanda Pedersen, Senior Staff Writer

The best cancer test is the one patients actually take, a point the U.S. Preventive Services  Task  Force  (USPSTF)  appears to have paid particularly close attention to in its updated colorectal cancer (CRC) screening recommendations, which were published ahead of schedule Wednesday in the Journal of the American Medical Association, along with several evidence reports and editorials. The final version of the guidelines included a key difference from the draft version released last October because the task force declined to express a preference in screening method and instead offered a list of acceptable screening strategies, including CT colonography (virtual colonoscopy) and multi-targeted stool DNA tests.

This change in the recommendations is especially significant for Exact Sciences Corp., because the task force removed  terms from its draft version that caught the company off  guard last year by  describing its Cologuard    stool-based DNA test as an “alternative” method that might be useful in “select clinical circumstances.” That news plunged Exact’s shares (NASDAQ:EXAS) 46 percent to close at $9.98 the day the draft statement was published because it created ambiguity that likely would have affected insurance reimbursement of the test.

Not only did the task force edit the term “alternative” out of its final recommendations, the authors also addressed the concerns that the draft had raised last year. The task force recognized that “a sizable proportion of the eligible U.S. population is not taking advantage of this effective preventive health strategy” and noted that “there is no one-size-fits-all approach to colorectal cancer screening.”

The final version of the guidelines is intended to “provide clinicians and patients with the best possible evidence about the various screening methods to enable informed, individual decision making,” the authors wrote.

The revision also impacts CT colonography tests, which also were categorized as an alternative screening method  in the draft version. According to the task force,   nearly one-third of U.S. adults have never been screened for CRC and “offering choice” in screening strategies may increase uptake. The rest of the statement is largely as expected, with the task force continuing to recommend CRC screening for people between the ages of 50 and 75 (considered an “A” recommendation). The decision to screen older adults, between the ages of 76  to 85, should be individualized based on screening history and overall health status (a “C” recommendation), the task force  said.

Exact Sciences CEO Kevin Conroy said the final recommendations provide “an important level of clarity” that Cologuard should receive the benefits given to A-rated preventive services under the Affordable Care Act.”

The news sent the Madison, Wis.-based company’s shares up about 33 percent to $12.50 Wednesday, but the stock dropped back down and closed at  $9.33.

The recommendations also include the recently FDA-approved Epi Procolon assay, a liquid biopsy performed with a blood sample, from Berlin-based Epigenomics AG.

Durado Brookes, managing director of cancer control intervention, prevention and early detection for the American Cancer Society (ACS), pointed out that the recommendations are “very similar” to a 2008 joint guideline from the ACS,   a U.S. multi-society task force on CRC and American College of Radiology (ACR). “These guidelines reinforce the notion that with several test options, the best test is the one you get,” Brookes said.

The ACR also responded to the final recommendations on CRC screening and noted that, under the Affordable Care Act, private insurers are now required to fully cover (without a co-pay) all of these USPSTF-recognized CRC screening exams.

“A third of those who should be screened for colorectal cancer still choose not to be tested. Patients need more fully-covered screening options if we are going to reduce colorectal cancer deaths,” said William Thorwarth, CEO of the ACR. “Private insurers and Medicare should now fully cover virtual colonoscopy and the other USPSTF-recognized exams.”

The USPSTF said it reviewed evidence on the effectiveness of screening with colonoscopy, flexible sigmoidoscopy,CT colonography, the guaiac-based fecal occult blood test, the fecal immunochemical test, the multi-targeted stool DNA test and the methylated SEPT9 DNA  test.

The task force evaluated the tests in terms of reducing  the incidence of and mortality from colorectal cancer or all-cause mortality, the harms of these screening tests, and the test performance characteristics for detecting adenomatous polyps, advanced adenomas based  on size, or both, as well as colorectal cancer. The USPSTF also commissioned a comparative modeling study to provide information on optimal starting and stopping ages and screening intervals across the different available screening methods. //

New data underscore benefits of idebenone in DMD as Biomarin pulls drisapersen MAA


By Cormac Sheridan Staff Writer

Thursday, June 2, 2016

DUBLIN – Even as Biomarin Pharmaceutical Inc.’s dwindling hopes for its exon-skipping pipeline in Duchenne muscular dystrophy (DMD) turned to ash this week, with the withdrawal of its marketing authorization application (MAA) for drisapersen from the EMA, there was also some positive news for DMD patients and their families. Santhera Pharmaceuticals AG released additional clinical data from its Delos phase III study of Raxone (idebenone) in Duchenne muscular dystrophy (DMD), which showed that the drug’s ability to slow the rate of decline of respiratory function over one year converted into a range of clinical benefits.

The new analysis forms part of its recently completed regulatory filing in Europe and its planned filing in the U.S. The Liestal, Switzerland-based company filed for approval in DMD in Europe Tuesday, as a type II variation to its existing approval for treating visual impairment in Leber’s hereditary optic neuropathy. If the FDA is agreeable, it could complete a rolling new drug application during the third quarter of 2016 – although that depends on the outcome of a meeting in late July.

The primary endpoint of the Delos trial, which recruited 64 DMD patients who were not on concomitant glucocorticoid therapy, was the alteration in lung function over the one-year trial, as measured by the percentage change from baseline to week 52 in peak expiratory flow (PEF) for each patient. PEF for those in the drug treatment group declined by an average 2.57 percent, whereas it declined by an average 8.84 percent for those in the control group. (See BioWorld Today, May 14, 2014.)

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