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New Clinical Review Guidance on FDA’s 2019 Agenda, Gottlieb says

March 4, 2019

For the first time in 20 years, the FDA will update its guidance on how clinical investigators should conduct trials, Commissioner Scott Gottlieb told a key House appropriations subcommittee last week as the lawmakers begin the process of developing next year’s budget.

The revised guidance is part of the FDA’s efforts to modernize the way it looks at clinical evidence of a drug’s effectiveness and safety, Gottlieb said. Much has changed in the science and data in the past 20 years, but the agency’s approval standards remain unchanged, he said.

Now, Gottlieb said, “We have much more opportunity to use a broader array of data as confirmatory evidence to help support product review. This includes real-world evidence and real-world data.”

In addition to the new guidance, Gottlieb said the FDA plans to “update our approach to drug review across every stage in the life cycle of a new innovation, from the time an investigator first asks the FDA for permission to begin the clinical testing of a new drug to how we continue to assess the safety and effectiveness of new medicines after they’re approved by the agency.”

Beginning in the next few months, CDER will adopt new standard templates for its 30-day IND safety reviews and protocol reviews, Gottlieb added. This will better integrate the work of clinical and scientific reviewers and will improve the consistency of the IND reviews. It will also provide greater predictability to product developers, he said.

And the agency will expand its Adverse Event Reporting System to contain premarket safety data, including IND safety reports on serious unexpected adverse reactions in clinical trials and generic bioequivalence trial safety reports.

“The aim is to make the entire process more structured and predictable,” Gottlieb said.

FDA Issues Draft Guidance on Bioavailability Trials
Sponsors may want to think about pilot trials to establish bioavailability or bioequivalence of a proposed treatment to help sponsors gauge appropriate time intervals to collect samples, and to determine the “washout periods” for a proposed treatment, among other things, says a new draft guidance from the FDA.

The agency also recommends that bioavailability trial sponsors only recruit healthy subjects. If there are safety concerns, patients may be enrolled, but only when their “disease is expected to be stable for the duration of the study.”

When finalized, the guidance will replace the FDA’s March 2014 draft guidance on bioavailability and bioequivalence studies submitted in NDAs or INDs.

Read the draft guidance here: https://bit.ly/2EyJdzy.

Roche Pays $4.8 Billion for Spark, Expands Gene Therapy Portfolio
Roche has agreed to acquire Philadelphia-based gene therapy company Spark Therapeutics, in a deal valued at nearly $4.8 billion, the two companies announced last week.

It’s another sign that the advanced therapy market is maturing: In 2017, Spark, a startup founded just four years previously, won approval for its Luxturna (voretigene neparvovec-rzyl), a treatment for retinal dystrophy. It was the first gene therapy to win approval in the U.S. and Europe for a genetic disease.

Spark has four other therapies in clinical trials. Two of them — SPRK-7001 for Choroideremia and SPK-8016 for hemophilia A with inhibitors — are in early phases and two others — SPK-9001 for Hemophilia B and SPK-8011 for Hemophilia A — are in Phase III. The hemophilia trials are being run in cooperation with Pfizer.

Roche hopes to close the deal by the second quarter.

FDA Revises Guidance on Testing Effect of Food on Drugs
Clinical trial sponsors should assess the effect of food on a new drug before conducting pivotal safety and efficacy trials, the FDA said in a new draft guidance.

The agency calls for preliminary assessments on the effect of food on new drugs during Phase I pilot trials to determine whether the drug should be administered with food in clinical trials until they can identify a to-be-marketed formulation.

Read the full guidance here: https://bit.ly/2SYx1kq.

UK Issues New Guidelines for Trials Transparency
The UK has laid out 10 new regulations to bring needed sunlight to clinical trials.

Last year, it emerged that few clinical trials in the UK were sharing their data publicly, and the government promised to overhaul the rules. The new report from Undersecretary of State for Health Nicola Blackwood, issued Tuesday, is the first step.

The top recommendation is that the government “explicitly commit” to adopting EU rules, which are scheduled to take effect in Europe shortly after Brexit in March. It also recommends that:

  • universities be required to report any trial data from their campuses to the relevant public authorities;
  • Public Health England, the government regulatory body, explain why it has failed to report results from trials it had funded or supervised; and
  • The government’s top health research agency be given funds for a national audit of trial data sharing, and that the agency be given legal authority to punish trial leaders who flout reporting requirements.

Pfizer Reduces Xeljanz Doses After Trial Signals Clotting Dangers
Drug giant Pfizer is reducing Xeljanz doses for patients in an arthritis trial after it was discovered that the higher dose may be causing blood clots in the lungs and even deaths.

Xeljanz (tofacitinib) has been on the market since at least 2012, but the FDA required a clinical trial among rheumatoid arthritis patients to test the risk of heart problems, cancer and opportunistic infections. Patients were given two doses — 10 mg and 5 mg, respectively — in combination with methotrexate.

In a public warning issued Tuesday, the FDA says that an external data safety monitoring committee “found an increased occurrence of blood clots in the lungs and death in patients treated with tofacitinib 10 mg twice daily compared to patients treated with tofacitinib 5 mg twice daily or a TNF inhibitor.”

Xeljanz has been approved for psoriatic arthritis and ulcerative colitis patients. The safety trial will continue, the FDA says.