FDA+ roundup: ALS bill would provide $100M annually to access potential drugs; FDA needs to better enforce ClinicalTrials.gov reporting, researchers say
The House Energy & Commerce Committee began marking up a dozen bills on Wednesday morning including one that would require the FDA to craft a five-year action plan for fostering the development of drugs that improve or extend the lives of people living with rare neurodegenerative diseases.
Rare neurodegenerative diseases, like amyotrophic lateral sclerosis or ALS, have been historically very difficult to treat. But this bipartisan bill, introduced by Rep. Mike Quigley (D-IL), will provide $100 million for each of fiscal years 2022 through 2026 to help HHS award grants to facilitate access to investigational drugs that diagnose or treat ALS.
The FDA will award grants to public and private entities to cover the costs of R&D for drugs that diagnose or treat ALS and other severely debilitating neurodegenerative diseases, the bill text says.
In addition, HHS would have to establish the Public-Private Partnership for Neurodegenerative Diseases between the NIH, FDA, and at least one eligible entity (generally, an institution of higher education or a nonprofit organization). The bill, first introduced last summer, also has a companion bill in the Senate, introduced by Chris Coons (D-DE).
FDA needs to better enforce ClinicalTrials.gov reporting, Yale researchers write in JAMA
Despite clear instructions on how and when to report clinical trial results, about 60% of trials fail to report results on time and more than 30% (among almost 3000 clinical trials with primary completion dates between Jan. 2017, and Jan. 2021) have not yet reported results. That lack of reporting means the FDA needs to beef up its enforcement efforts, researchers from Yale wrote recently in a JAMA viewpoint.
For its part, the FDA identifies potential violations of the law governing the reporting of the results through investigations and third-party complaints, and then at its discretion, may issue a Preliminary Notice of Noncompliance informing responsible parties of potential violations.
Yale researchers used FOIA to find that the FDA has only issued 58 of its preliminary notices of noncompliance from 2013 through April 29, which they said is “a tiny fraction of the thousands of FDAAA-applicable clinical trials identified as noncompliant with results information reporting requirements as of January 2021.”
So how can the FDA help? The researchers say that instead of relying on inconsistent BIMO investigations and third-party complaints to identify noncompliant trials, the FDA could instead use a continually updated list of FDAAA 801 problems maintained by the NIH. In addition, FDA should publicize the notices more frequently and ensure that they present clear timelines for further enforcement actions if results remain unreported.
“The FDA can and should harness its enforcement tools to ensure timely submission of trial results information to ClinicalTrials.gov. By doing so, the FDA could bring important missing results to light and demonstrate its commitment to protecting patients through clinical trial transparency,” they wrote.
Regeneron and Novartis seek tweaks to ICH’s S12 guidance for gene therapies
Novartis, Regeneron and others are suggesting tweaks in recently released comments on a recent guidance from ICH, known as S12, which deals with the nonclinical biodistribution considerations for gene therapies.
Novartis, for instance, took issue with the fact that viral shedding is listed as “out of scope” from the S12 guidance.
“We believe that it is a missed opportunity in not including this topic, particularly as some would consider shedding as part of the ‘distribution’ of a gene therapy vector. In addition, there exists significant health authority divergence in opinion with respect to whether shedding should be assessed in nonclinical studies. Please consider adding shedding within this guidance,” Timothy MacLachlan, executive director of pre-clinical safety, and Jessica Rizzo, regulatory policy manager, wrote.
And while the guidance suggests that nonclinical BD should be assessed prior to the initiation of a clinical trial, Novartis wonders what to do in a situation where a sponsor is attempting to open an IND with an interim look on a much longer-term animal study, where sponsors would get additional information for the clinical trial from that animal study.
Regeneron, meanwhile, is seeking clarity on the ICH recommendation for sample collection of a core panel of tissues/biofluids. The New York biotech added:
The guidance could be read as recommending that all of the listed tissue samples should be collected. Instead, Regeneron proposes that the guidance should recommend a risk-based approach to guide which samples should be collected along with appropriate justification provided by the developer, based on knowledge of the gene therapy product and its target(s). The same risk-based approach could be used to determine which of the collected tissues would be analyzed. Doing so would allow developers to identify those sample tissues that can provide early scientific evidence that could inform future in-human trials.
FDA must promptly punish Minnesota Hospital researchers, Public Citizen says
Public Citizen, a nonprofit consumer advocacy organization, filed a citizen petition on Wednesday with the FDA, calling on the agency to take swift enforcement action against several Minnesota doctors cited in recent warning letters who conducted clinical research of dangerous drugs without the proper authorizations in place.
According to a warning letter sent by FDA in October, doctors never filed the appropriate INDs for the ketamine trials with the FDA, as required by law, and didn’t write appropriate protocols to ensure that children and pregnant women weren’t enrolled. The trials also didn’t exclude those who were under the influence of intoxicants, in whom the use of ketamine is cautioned.
“A slap-on-the-wrist approach for such noncompliance that significantly violated the rights of more than 1,700 vulnerable human subjects and endangered the health of safety of many of these subjects will not suffice,” Public Citizen wrote.