FDA: Novel Trial Design Meetings

September 4, 2018

Drug sponsors wishing to take part in the FDA’s pilot meeting program to discuss complex innovative trial designs (CIDs) with agency staff may now file meeting requests.

New Scale for Tumor Treatments

August 27, 2018

Europe’s largest oncologist association has approved a new scale to measure tumor DNA mutations, a move that backers hope will simplify and standardize choices for targeted cancer treatments and clinical trials.

First Human Zika Vaccine Trial

August 20, 2018

Researchers are launching the first human trial of an experimental live Zika vaccine. The vaccine, which contains a weakened version of the virus, was de­veloped by scientists at the National Institute of Allergy and Infectious Diseases (NIAID). The trial plans to enroll a total of 28 healthy, non-pregnant adults, ages 18 to 50, at Johns Hopkins School of Public Health Center for Immunization Research and at the Vaccine Testing Center at Larner College of Medicine at the University of Vermont. Trial participants will be randomly assigned to receive a single subcutaneous dose of the experimental vaccine (20 participants) or a placebo (eight participants). Neither they nor investigators will know who is receiving the real thing. Participants will keep track of their tem­perature on diary cards at home – and return to the clinic for periodic checkups for about six months. Researchers will take blood samples during visits to see if they’re developing antibodies in response to the vaccine. Anna Durbin, a professor of International health at Hopkins School of Public Health, is leading the Phase I clinical trial. Most people infected with the Zika virus — primarily transmitted by certain mosquitoes — have mild to no symptoms. But it can cause serious birth defects and developmental problems in babies born to women infected during pregnancy. That’s why the Centers for Disease Control and Prevention advises women who are pregnant or planning to become pregnant not to travel to areas with a known Zika risk. “Zika virus infection remains a significant threat to pregnant women and their developing fetuses, and we can expect to see periodic outbreaks and cases in areas where Aedes aegypti mosquitoes thrive,” said NIAID Director Anthony Fauci. “NIAID remains committed to developing safe and effective Zika vaccines, and we are pleased to begin clinical testing of a live attenuated candidate.”

FDA: Focus on Hardest to Treat in Cohort Cancer Trials

August 13, 2018

The FDA says sponsors considering adaptive studies for early phase cancer treatments should focus on patients with no other options. The agency notes that so-called expansion cohort trials — which start out relatively small but expand if a potential treatment shows promise — can be a way to get a treatment to market more quickly. The thinking is, the more participants in earlier trials the more likely it is to find and fix (if possible) glitches — ensuring faster approval or scrapping the potential treatment in its infancy if it doesn’t work or if risks outweigh benefits. “A lot of time and cost of clinical development is spent waiting in between the start and end of the phases of trials,” FDA Commissioner Scott Gottlieb said in a statement. “Expansion cohort trials can bring efficiency to drug development, potentially reducing development costs and time.” In a 17-page draft guidance released last week, the FDA says it wants to “establish an infrastructure” designed to help sponsors use cohorts to speed drug approvals without compromising safety. Its top recommendation: Focus on patients who are most seriously ill and don’t have any other treatment options. The agency also encourages researchers to hire centralized data management committees and IRBs and have them meet regularly to discuss latest findings and best next steps. “It is critical that investigators, IRBs and regulators are updated with new safety information so that they can provide the necessary oversight for the protection of human subjects and so that investigators can ensure that patients can provide adequate informed consent,” the draft document says. The jury’s still out on the effect of expansion cohorts. A 2017 study by Texas researchers, published in the Journal of the American Association for Cancer Research, analyzed 533 Phase I cancer trials between 2006 and 2011. They found the ones that used expansion cohorts went on to have successful Phase II trials at nearly twice the rate (48 percent) as studies that didn’t (27 percent). But just a year earlier, a team of Cleveland researchers analyzed 252 cancer trials conducted between 2004 and 2014 and found expansion cohorts made little or no statistical difference between success or failure in Phase II trials. Read the FDA’s draft guidance here:

FDA Signs Off on Treatment for Rare Adrenal Gland Tumors

August 6, 2018

The FDA has approved the injectable drug Azedra for rare cancers of the adrenal glands — the first ever non-surgical therapy OK’d for these tumors. Azedra (iobenguane I131) is a radiotherapy drug that attacks tumors with a high, specifically targeted dose. It’s designed to treat adults and children (12 and older) with inoperable locally advanced or metastic cancers called phenochromocytoma and paraganglioma. Pheochromocytoma forms inside and paraganglioma grows outside the adrenal gland(s). Both tumor types release hormones that can cause symptoms including high blood pressure, rapid heartbeat and anxiety. University of Pennsylvania researchers gave 68 patients in a trial at least one therapeutic dose of Azedra. The results: 25 percent who received at least one dose and 32 percent of those who received two doses saw their blood pressure drop enough to cut their hypertension meds in half. “This is a true breakthrough. Until today, there were no anti-tumor therapies available for patients with these tumors who were not candidates for surgery,” said principal investigator Daniel Pryma, an associate professor of Radiology and Radiation Oncology. “This therapy not only controls the tumors but also the debilitating symptoms caused by their excess hormone production, meaning it provides dual benefit to patients,“ added Pryma, also chief of Penn’s Nuclear Medicine and Clinical Molecular Imaging. Reported side effects include low white blood cell and platelet counts, fatigue and anemia. The FDA gave Azedra an Orphan Drug designation, Fast Track status and Breakthrough Therapy designation in the U.S. Its license is held by Progenics Pharmaceuticals.

FDA: Put Patients on Strict Diets in Trials for Metabolic Disorders

July 30, 2018

Sponsors studying genetic metabolic disorders should put patients on strict diets before clinical trials begin, the FDA says in a new draft guidance. Researchers have already developed drug treatments to complement the diets of people who suffer from such metabolic disorders as phenylketonuria, organic acidemia and urea cycle defects. But even small nutritional changes can affect clinical trial results, especially when a proposed drug’s impact is “relatively modest,” the FDA says. To address those challenges, the FDA recommends that participants in clinical trials be put on strict eating plans (that are clearly detailed) before studies start. While monitoring diets, sponsors should remember that the two most common assessments — food frequency questionnaires and food diaries — have limited value because they rely on “crude measures” and participant memory. The length of time participants spend on their pretrial diet should be based on their age, disorder (and its severity) and how complex the diet is, the guidance states. Patients with metabolic disorders often have to undergo surgeries, which, in turn, may require they go on specialized diets. Any surgeries should be completed well before a trial begins, the FDA says. The agency also discourages switchover trials in which patients are initially put on a special diet and then given a drug. “Without a concurrent control arm and blinding, switchover designs are unlikely to produce interpretable results,” the FDA says.Read the full guidance here:

FDA Issues New Guides on Use of Electronic Health Information in Clinical Trials

July 23, 2018

The FDA is urging researchers to work with electronic health record keepers to help improve clinical trial accuracy and efficiency. The agency doesn’t typically regulate companies or organizations that maintain electronic medical records (EMRs). But it says it’s weighing in to highlight and clarify ways electronic health record (EHR) systems can help clinical trials run more smoothly and use data from foreign studies conducted outside investigational new drug applications and device exemptions. In guidelines released July 18, the FDA encourages sponsors and investigators to use approved EHR or electronic capture data capture (EDC) systems to exchange key information, noting that doing so can dramatically speed up information sharing and precision.

Other FDA tips:

  • Sponsors and investigators should use EHR systems endorsed by the Office of the National Coordinator for Health Information Technology (ONC). If they lack access to ONC-certified systems, they should make sure security measures are in place to protect study data.
  • Study monitors should have easy access to “all relevant information” detailed in consent forms, including how long identifying records will be kept. (Federal law requires investigators to keep records from drug or human biological product trials for at least two years after marketing applications have been approved or trials have been scrapped and the FDA notified. Records relating to medical devices must be retained for at least two years after an investigation wraps up or after it’s determined they are no longer needed to support premarket approval applications or notices of completion.)

Read the FDA’s guidance here:

Roche Hails Phase III Study on Tecentriq, Chemo Combo

July 16, 2018

A Phase III study testing a combination of Tecentriq and chemotherapy as a first-line treatment for triple negative breast cancer has met one of its primary endpoints for progression-free survival, Roche announced. The trial is the first positive Phase III immunotherapy study for triple negative breast cancer, Roche said in a news release. Roche is testing Tecentriq in seven different Phase III trials. The drug is already approved for use in the U.S. for patients with previously treated metastatic, non-squamous, non-small cell lung cancer and for some kinds of metastatic urothelial carcinoma.

Real-World Evidence Returns ‘Limited,’ EU Review Finds

July 9, 2018

Hundreds of millions of public dollars in pursuit of real-world evidence (RWE) has produced “limited” returns, left wide knowledge “gaps” and often “diminish returns on the public funds invested,” a team of European researchers has concluded.

Gottlieb Says Cancer Drug Surrogate Endpoints Will Be Released for First Time

July 2, 2018

In the coming weeks, CDER will publish online a list of surrogate endpoints that led to the approval of oncology drugs and biologicals, FDA Commissioner Scott Gottlieb announced at the National Comprehensive Cancer Network Policy Summit in Washington, D.C. “We believe this list will help to address some of the questions that have been raised about how we apply surrogates to make a given regulatory decision,” he said. “We’ll also be taking steps to provide more guidance to drug developers on these novel approaches.” The guidance will include how to design clinical trials that are based on a biomarker as a novel surrogate endpoint, and the agency will accept sponsor requests for Type C meetings earlier in the drug development process. The meetings can be requested to discuss using a biomarker as a surrogate endpoint in contexts where the marker was never the driving force behind approval. The efforts will give innovators and researchers more clarity about how the agency uses endpoints — and how it expects developers to evaluate biomarkers as surrogate endpoints — in a given disease state, Gottlieb said.