TapImmune, Marker Therapeutics Close Merger

October 29, 2018

TapImmune says it has formally closed out its $70 million merger with private company Marker Therapeutics, a move the company says will help push T cell blood cancer therapies through clinical trials.

The combined company will keep Marker’s name but its incorporation will move from Nevada to Delaware.

“With the transaction completed,” Marker CEO Peter Hoang said in a statement, “we can now push our clinical trials forward more efficiently.”

The newly formed Marker plans to test several novel T cell therapies in Phase II trials. The combined company focuses on T cell immunotherapies for blood cancers and solid tumors.

Unlike CAR-T and TCR-based treatments, Marker’s T cells aren’t genetically engineered. Company officials say that makes the potential treatments significantly cheaper and easier to make. Marker also claims that early indications are its treatments are less toxic than its more complicated rivals.

Sites and Sponsors: A Failure to Communicate
SAN DIEGO—A debate over fair payment practices between sponsors and sites had each side asking the other to be more open about what was really going on.

Kelly Sheehan, portofolio sourcing manager for drug sponsor Astellas Pharma Global Development, and Hakim Mohamed, president and CEO of One Source Clinical & Management, had a spirited debate over site budgets here at the MAGI conference.

Sheehan fired the first volley, calling for sponsors to be more flexible about site budgets as long as sites explain why they need funding–and how they’re spending it.

“Sponsors should be willing to pay as long as you’ve got documented policies and procedures. If you don’t have that defensibility, you’re not going to get paid,” he said.

Mohammed countered, saying that sponsors have long since abandoned the practice of sending detailed spreadsheets and instead now have budgets with vague phrases such as “Day One Visit” which leaves sites wondering what a contract’s deliverables might be.

Sheehan said he’s seen trials in which a site’s “overhead” eats up half of the budget, leaving a sponsor in an untenable position. He suggested that sites consider setting aside a small portion of a contract — say, 10 percent — to be paid once the site has handed over all data and the trial officially ends.

Mohamed nixed the suggestion, noting that drug sponsors often sit on reserves for months at a time, which could hurt business, especially for smaller sites. “Why should we be begging for money we’ve already earned?” agreed a site exec on hand for the discussion.

Sites Still Reticent about Patient-Centered Trials
SAN DIEGO—Sites will have to overcome their fear over loss of control if the clinical trials industry is going to become truly patient-centered, said a panel of experts at last week’s MAGI conference.

Telemedicine, home care visits and other modern techniques can dramatically ease time and financial constraints on trial participants. But despite technology leaps, some trials still don’t lend themselves to remote monitoring, wearable apps or home care visits, said Michael Keens, chief operating officer at Firma Clinical.

“At the end of the day, it’s about comfort level,” he said.

But sometimes it’s just plain fear of letting go, said Jodie Huddleston, director of clinical trials at Coram Clinical Trials.

Her company found that things went much more smoothly when it began holding“kickoff meetings” where everyone involved in a trial — from principal investigators to home-health nurses — discuss their approach and ways to tackle and prevent any potential problems.

In trials involving home visits, the company trains at least two nurses, one as a primary and the other a backup, and sends out “delegation-of-authority” letters to detail the nurses’ expectations, and how (and to whom) their work will be reported.

There have been some speed bumps, said Huddleston, noting that even the best-run sites can hit snags.

Derek Ansel, clinical strategy lead at PRA Health Sciences, said that sites and sponsors should remember that the point of patient-centered care is to tailor trials to individual needs. That means everyone has to be up front about what can and can’t be done. A clinical trial in sub-Saharan Africa, for instance, might not be able to make use of broadband infrastructure, while patients in the UK might prefer to interact online rather than travel to a trial site.

Illustrating just how far the industry still has to go to get patient-centered trials right, panel moderator Matthew McCarty, global head of patient engagement at ICON PLC, asked how many sponsors in the packed conference room had talked to a patient before drawing up a trial protocol. Just one hand went up.

Bristol-Myers Invests $12M in Compugen for Combo Trials
Bristol-Myers Squibb has agreed to invest $12 million in Israeli drugmaker Compugen to help pay for clinical trials of a combination of Bristol-Myers’ Opdivo and Compugen’s investigational COM701, the companies have announced.

Under the agreement, announced earlier this month, Compugen will sponsor a two-part, Phase I trial testing the combination of Opdivo (nivolumab) and COM701, an antibody, as a treatment for non-small cell lung, ovarian breast and endometrial cancers.

Opdivo is an immunotherapy that became the first-of-its kind to win regulatory approval for a variety of cancers, beginning in July, 2014. It’s now approved in more than 60 countries.

See terms of the deal here:

Law Ups Clinical Trial Reporting
The FDA Amendments Act (FDAAA) significantly increased registration and results reporting of clinical trials, a new study found.

The FDAAA, enacted by Congress in 2007 to enable more comprehensive agency reviews, requires the registration of all non-phase I clinical trials involving FDA-regulated medical interventions on It also requires that their results be reported to the website within 30 days of drug approval.

Researchers from Yale and Harvard Medical School reviewed all efficacy trials supporting NDAs for neuropsychiatric indications between 2005 and 2014 to try to gauge the effect of the law on trial registration and reporting.

They found both went up significantly after the measure was enacted: Only 10 percent of trial results were submitted pre-FDAAA compared to all of them once it took effect. Similarly, the number of trials registered jumped from 64 percent to 100 percent.

“These findings have important implications for understanding the potential impact of the FDAAA, along with other initiatives that may have improved research reporting, and for developing future strategies to improve selective publication and outcome reporting more broadly,” the researchers said.

According to another recent study, nearly half of European Union clinical trials go unreported, with academic institutions most likely to fail to submit the data (CWW, Sept. 17).

FDA Drops Proposed Rule on Reporting Falsified Trial Data
The FDA has scrapped a proposed rule that would have required drug sponsors to report possibly fabricated data in their clinical trials.

The now-defunct measure — first introduced in February 2010 — would have amended regulations to require sponsors to report any evidence showing clinical trial data or results may have been doctored.

The FDA determined the proposed rule was no longer needed to protect research subjects or ensure the integrity of clinical trial data used to support marketing applications and requests for product approvals.

Under current regulations, study sponsors are required to notify the agency when they terminate clinical trials and provide a comprehensive account of their actions — and institutional review boards must inform the agency when they suspend or end research they approved.

“Based on our review of recent data, we conclude that we are receiving adequate notice of falsification of data, and we do not believe that adopting the proposed requirements would provide us with substantial additional information,” the agency said.

The FDA stressed its decision doesn’t mean it won’t develop tougher clinical trial reporting rules in the future.

The withdrawal notice was included in the agency’s semi-annual regulatory agenda, which lists planned rulemaking actions.

ICH M9 Guidance: Ways to Waive In Vivo Bioequivalence Trials
The International Council for Harmonisation (ICH) has released a draft guideline explaining how sponsors can waive in vivo bioequivalence clinical trials using the Biopharmaceutics Classification System (BCS).

The BCS-based biowaiver approach – which is only applicable for drugs in immediate-release oral dosage forms with systemic action – is designed to reduce the need for in vivo BE studies. Through the BCS biowaiver, in vivo BE trials may be waived if a sponsor’s data shows equivalence for in vivo performance.

In vivo bioequivalence (BE) studies are necessary to show that significant formulation changes in a drug’s bioavailability haven’t occurred during development; they’re also needed during generic development and for post-approval line extensions. But assurance of in vivo BE findings can be achieved through the use of extensive in vitro studies when sponsors use the drug’s critical properties and apply the BCS framework.

The BCS sorts drugs into one of four classes based on their ability to dissolve in water and their intestinal permeability:

  • Class I (high solubility, high permeability);
  • Class II (low solubility, high permeability);
  • Class III (high solubility, low permeability);
  • Class IV (low solubility, low permeability);

BCS-based biowaivers apply to highly soluble drugs that exhibit either high permeability (BCS Class I) or low permeability (BCS Class III). In assessing permeability, sponsors should focus on the extent of absorption derived from human pharmacokinetic studies, e.g. absolute bioavailability or mass balance.

“Higher permeability can be concluded when the absolute bioavailability is greater than or equal to 85 percent,” the guidance says, noting that if high permeability cannot be demonstrated, the drug should be considered to have low permeability.

The guideline doesn’t pertain to drug products with a narrow therapeutic index, while fixed-dose combination products are eligible if all of their drug substances meet guideline criteria.

Read the ICH guideline here:

Christine Pierre of SCRS Dies at 60
Christine Pierre, a veteran advocate for sites and CEO of RxTrials, has died after battling cancer for more than a year. She was 60.

Pierre had been a volunteer for the Association of Clinical Research Professionals before chairing ACRP’s board of trustees in 2007.

In 2012, she founded the Society for Clinical Research Sites, which grew out of her work six years earlier organizing the first Global Site Solutions Summit.

Pierre was diagnosed with ocular melanoma in 2017. She underwent surgery and got a positive prognosis. But in early 2018, the cancer metastasized to her liver.

She worked right up until the end. In mid-October, she was still handing out excellence awards to her society’s members. “Her contribution to furthering the sustainability of clinical research sites is unmatched,” the Society said in a news release announcing her death.

A memorial was scheduled for Oct. 29 in her hometown of Bowie, Maryland.

Pa. to Reimburse Trial Participants
Legislation is poised to become law in Pennsylvania that will allow patients to be paid for enrolling in clinical trials.

Pennsylvania is the second state to pass such a measure, following California which made the move last year. Similar bills are pending in Texas, Florida and Massachusetts.

Early this year the FDA issued a fresh guidance saying that paying patients “is a common and, in general, acceptable practice.”

Pennsylvania’s law now heads to the desk of Gov. Tom Wolf, who is expected to sign it.

Most of the heavy lifting has been done by the nonprofit Lazarex Foundation, which has lobbied regulators and lawmakers to stop thinking about trials payments as a form of coercion but rather as a way to help patients overcome financial, travel and other recruiting obstacles.

The regulatory and legislative victories have allowed the foundation “to re-frame our discussions with drug companies,” the group said in a news release. Drug companies have traditionally balked at paying patients because of fears that they could be accused of coercion.

WCG’s MedAvante-ProPhase: New Team of Clinical Leaders
MedAvante-ProPhase has hired eight new central nervous system experts to help the company advise clients running neurodegenerative and behavioral health trials.

The stable of sages will allow MedAvante-ProPhase “to bring even greater scientific and therapeutic expertise to the support of our clients,” said Donald A. Deieso, executive chairman and CEO of WCG, MedAvante’s parent company. “There is simply no substitute for decades of clinical experience.”

The new clinical leaders are:

  • Leslie Citrome, a clinical professor of psychiatry and behavioral sciences at New York Medical College, who has focused her practice on schizophrenia;
  • Christoph Correll, a professor of psychiatry at Hofstra/Northwell’s medical school, whose work has focused on severe psychiatric disorder;
  • Andrew J. Cutler, the chief medical officer at Meridien Research, who has focused on ADHD, depression, anxiety, bipolar disorder, schizophrenia, and other conditions;
  • James E. Galvin, a professor of integrated medical sciences and associate dean for clinical research at Florida Atlantic University’s medical school, who specializes in healthy brain aging, cognitive health, memory loss, Alzheimer’s disease and other forms of dementia;
  • Scott J. Hunter, a professor of psychiatry and behavioral neuroscience at the University of Chicago. His work has focused on childhood diseases and disorders;
  • Michael R. Liebowtiz, a professor of clinical psychiatry at Columbia University and founder of the first-of-its-kind Anxiety Disorders Clinic at the New York State Psychiatric Institute, who is considered an expert in social anxiety;
  • Philip Scheltens, a professor of cognitive neurology and director of the Alzheimer Center at the VU University Medical Center in Amsterdam, who concentrates on Alzheimer’s disease and other forms of dementia; and
  • Leo Verhagen Metman, a professor at Rush Medical College in Chicago, who is an expert in Parkinson’s disease.

Court Dismisses Lawsuit Over Clinical Trial Informed Consent
For the second time, a federal court dismissed a nonprofit’s lawsuit seeking to compel the FDA to amend its informed consent rules for clinical trials.

Last October, the Center for Responsible Science joined several clinical trial participants in suing the agency for denying a 2014 citizen petition that called on the agency to require that potential trial subjects be informed if the drugs they would receive had been predominantly tested in animal models, which can be unreliable predictors of effects in humans.

The FDA denied the petition, saying they were overbroad and would conflict with the flexibility needed for informed-consent disclosures.

In April, Judge James Boasberg of the U.S. District Court for the District of Columbia ruled that CSR lacked standing to sue but gave the nonprofit 30 days to amend its complaint.

The amended complaint included more detail and alleged the FDA’s petition denial caused CSR specific injury by forcing the nonprofit to pay a full-time employee to monitor clinical trials for deaths or serious adverse events.

In an Oct. 22 ruling, Judge Boasberg dismissed the lawsuit for the second time, noting that the group conducted such activities before the agency denied its petition.

CSR admitted it had only begun contacting principal investigators in May 2018, more than a year after the denial of the petition and only two weeks after the court gave it the chance to amend its complaint.

Read the ruling here: 

FDA: Generic Skin Patch Trials

October 15, 2018

Generic drug developers that use patches, inhalers, eye drops or similar means to deliver meds should hold clinical trials to test for potential side effects of skin irritation and, in the case of patches, adhesion quality, the FDA says.

FDA Lifts Holds on Trials

October 1, 2018

The FDA has lifted holds on two sets of clinical trials, one for an experimental treatment of several cancers and the other a gene therapy targeting Duchenne’s muscular dystrophy.

Breast Cancer Trial Resumes

September 24, 2018

Mersana says it has worked out a new agreement with the FDA to resume recruiting patients for a clinical trial of its breast cancer drug months after one of the participants died.

FDA Tackles Device Uncertainty in Clinical Trials

September 10, 2018

The FDA may accept some uncertainty about the safety of a proposed medical device if sponsors carefully collect and report data after it hits the market, the agency says in new draft guidance.