FDA Seeks Comments on Trial Surrogate Endpoints

November 5, 2018

The FDA is seeking public comments on an updated table for surrogate endpoints for clinical trials.

The table lists surrogate endpoints for diseases from cancer to osteoporosis and is designed to help speed drug development by giving sponsors a reference guide to consider when setting up trials.

Read the agency’s notice in the Federal Register here:

Eli Lilly, Dicerna Cut RNAi Deal
Eli Lilly has agreed to pay $100 million up front and provide as much as $3.6 billion more in incentives for Dicerna’s RNA interference technology, GalXC.

Under the terms of the deal, Lilly will offer up to $350 million for certain clinical trials and commercialization milestones, as well as product royalties in the mid-single to low-double digits on product sales.

In return, Dicerna will offer Lilly exclusive access to GalXC on treatments for neurodegenerative and pain disorders as well as unspecified cardio-metabolic diseases.

The Lilly deal comes just days after Dicerna announced that it had sold two of its preclinical RNAi therapies to Alexion for $22 million.

Drug Company Seeks Chinese Approval for Alzheimer’s Drug
Shanghai-based Green Valley Pharmaceutical Company says it’s seeking a new drug application and market authorization from Chinese regulators for a dementia drug after a successful Phase III clinical trial.

Green Valley tested 818 patients with mild-to-moderate Alzheimer’s disease across 34 sites in China. Patients were randomly given either an oral placebo or 450 mg Green Valley’s GV-971, a multi-targeting carbohydrate-based drug, twice daily for 36 weeks.

At the end of the trial, patients in the GV-971 group showed statistically significant improvement in cognitive function.

The trial was led by researchers at Shanghai Jiao Tong University in Shangai and Peking Union Medical College Hospital in Beijing.

Feds Pause Heart Stem Cell Clinical Trial, Citing False Data
The federal government has halted ongoing clinical trials of heart stem cell transplants amid concern they’re based on fabricated research.

The CONCERT-HF trial had hoped to recruit 144 heart attack patients for a Phase II trial to determine whether stem cells could be used to help restore damaged heart tissue. The trial began in October 2015, and was scheduled to run through May2020.

But the National Heart, Lung and Blood Institute announced last week that it’s hitting the pause button, “out of an abundance of caution,” after allegations of faulty data surfaced.

At the center of the controversy is Piero Anversa, 80, a former Harvard Medical School and Brigham and Women’s Hospital researcher once hailed for claiming to have found a way to grow new heart cells to replace muscle injured in heart attacks and heart failure.

In April 2017, Brigham and Women’s paid $10 million to the federal government to settle claims that Anversa and two members of his team had used phony data to win government funding for his research.

The Department of Justice alleged that the researchers knew or should have known that their work included “improper protocols, invalid and inaccurately characterized cardiac stem cells, reckless or deliberately misleading record-keeping, and discrepancies and/or fabrications of data and images.”

The hospital and Harvard have since demanded that more than 30 of Anversa’s papers be retracted.

Anversa was not directly involved in the CONCERT-HF trial but his work underpins the effort. The trial’s data and safety monitoring board will review the safety of the trial “as expeditiously as possible and will inform” the government’s “future actions” to “ensure the highest standards of participant safety and scientific integrity,” the institute said in its announcement.

New v. Old Shingles Vaccine
The recently released shingles vaccine is much more effective than the older one but carries a greater risk of mild side effects, a new study finds.

Canadian researchers reviewed results of clinical trials involving more than two million people ages 50 and older and found that the adjuvant, recombinant subunit vaccine – brand name Shingrix – was 85 percent more successful than Merck’s live attenuated Zostavax at preventing the condition.

It was also 30 percent more likely to cause redness or swelling at the injection site. But there weren’t any statistically significant differences between the two vaccines for serious adverse events or deaths, according to the BMJ.

The FDA approved GlaxoSmithKline’s Shingrix late last year.

The CDC recommends healthy adults 50 and older get the Shingrix vaccine instead of Zostavax – which has been used since 2006. It’s given in two doses separated by two to six months.

Read the study here:

Inspire Gives Patients a Voice in Drug Development Process
Inspire, the nation’s leading health social network, last week launched new solutions aimed at giving patients a voice in the drug development process.

Inspire Insights is designed to help the life sciences industry blend real-world patient evidence and strategic research — a move encouraged by the FDA as a way to speed drug development and boost clinical trial recruitment and retention, says Monica St. Claire, a linguist and Inspire Insights’ product lead.

She notes that Inspire, which creates and manages online communities for one-million-plus patients and caregivers, has a unique dataset on the patient experience that can be used to help solve some of the biggest clinical trial challenges and serve as a how-to on patient centricity for R&D, government, treatment center and commercial stakeholders.

“We have the ability to speak directly with our community members, gather and quantify their opinions and perspective in surveys, and learn from publicly shared content on Inspire and the other key sources of social media activity,” St. Claire said.

“This means we can select and combine the best methods with real world patient and caregiver voice data to deliver business-changing insights and recommendations–including everything from optimized and compelling messaging, to informed and improved trial designs that better accommodate patients, include more meaningful outcomes, and require fewer amendments, which can delay trial progression and ultimately delay a treatment reaching patients,” she added.

The company already had an Insights solutions product for commercial brand managers that it’s now expanding to also help life sciences companies quickly and cost-effectively gather patient feedback, said Jeff Terkowitz, Inspire’s VP of product.

Inspire is hosting a free webinar Nov. 8 to introduce its new research solutions to industry leaders. To register, link to:

FDA: Hep B Draft Guidance
Clinical trials of drugs for treatment of chronic hepatitis B viral infections may use multiple efficacy endpoints, the FDA said in new draft guidance released last week.

The endpoints can include the suppression of hepatitis B virus (HBV) DNA on-treatment, the agency said. Other endpoints could include suppression of HBV DNA for more than six months off-treatment after an initial therapy period and sustained suppression off-treatment with loss of HBV surface antigens.

Liver disease progression is an important endpoint, but assessing it can be challenging as the endpoints can occur infrequently until late in the course of chronic HBV progression. However, treatment effects on such endpoints often result in useful clinical data that could support expanding the indication or patient population, the agency said.

In these cases, potential outcomes for assessment include change in model for end stage liver disease scores, progression to either fatal liver failure or liver failure requiring transplantation, and occurrence of hepatocellular carcinoma. “Treatment-related regression of fibrosis or cirrhosis, as assessed by liver biopsy or noninvasive methods, can also be appropriate for display in the label and should be discussed with the division when protocols evaluating these endpoints are being designed,” the guidance states.

The primary efficacy analysis for HBV drugs should compare the proportion of patients responding to therapy across treatment arms. Sponsors should do everything in their power to retain trial participants. But if patients do drop out, sponsors should try to follow up with them and explain the missing data.

It could skew results if the analysis excludes these patients because outcomes may have major differences between patients who complete protocols and those who don’t. So the statistical analysis plan should specify how the sponsors will handle missing data, the agency said.

Read the draft guidance here: 

FDA Hits Hennepin IRB with 483 for Ketamine Clinical Trials
The FDA has issued a Form 483 to the Hennepin County Medical Center’s IRB for approving studies for waiver of informed consent without determining that those studies met the waiver criteria, allowing patients in clinical trials to receive ketamine and other sedatives without their approval.

According to the FDA, the hospital also approved trials including vulnerable patients without determining if additional safeguards had been put in place to protect those patients.

And, “the IRB used an expedited review procedure for research which did not appear in an FDA list of categories eligible for expedited review, and which had not previously been approved by the IRB,” the 483 says.

The IRB’s August inspection was prompted in part by Public Citizen’s call for the FDA and OHRP to investigate the hospital’s ketamine studies and earlier news reports that the drugs were being improperly administered.

Officials at Hennepin could not be reached for comment, but have issued public statements that the hospital has not yet formally responded to the FDA.