The expedited approval pathways implemented by the FDA in the past 30 years have shortened many drugs’ road to market, but a new study from Harvard University researchers questions whether the time saved outweighs the risks of approving new drugs without putting them through the traditional clinical trial process.
Of all drugs approved by the FDA in 2018, 81 percent followed at least one of the expedited pathways, according to the study published on the Journal of the American Medical Association online information service, JAMA Network.
Two of the programs in particular have relaxed the agency’s usual rigorous standards of evidence. The Fast-Track designation allows sponsors to submit new drug applications without data from phase 3 efficacy trials, the study’s authors say,
and the Accelerated Approval pathway allows the use of surrogate measures that may be “only reasonably likely to predict clinical benefit” as substitutes for traditional endpoints.
The result of this regulatory flexibility, the study’s authors say, is that the number of approvals based on data from at least two pivotal trials has decreased dramatically in the past 25 years. In the period from 1995 to 1997, 80 percent of approved drugs had undergone the traditional trial process. By 2015, that number had decreased to 52.8 percent.
The Breakthrough Therapy designation has been increasingly popular with sponsors because it encourages alternative clinical trial designs that may be smaller and faster to complete. Under this program, average development times have decreased from 8 years to 4.8 years. But the researchers argue that because this program’s name implies “a large magnitude of benefit,” its approved drugs have been misinterpreted as having “higher levels of efficacy than has necessarily been demonstrated.”
And although sponsors qualifying for the Accelerated Approval pathway are required to conduct postapproval studies to verify their drugs’ clinical benefit, the researchers say the rate of completion has been inadequate, pointing out that by 2015 only 54 percent of studies required of sponsors in 2009 and 2010 had been completed and 20 percent had not even been started.
The researchers call for Congress, the research community or both to periodically reevaluate the balance between approving drugs more quickly with less clinical evidence and the risk of rushing potentially unsafe products to market.
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Biogen has agreed to purchase Pfizer’s early-stage neurological disease drug and initiate a phase 1b clinical study of the experimental drug in the fourth quarter
The company plans to develop the CK1 inhibitor, PF-05251749, for treating sundowning in Alzheimer’s patients and irregular sleep-wake rhythm disorder in Parkinson’s patients.
Biogen will pay Pfizer $75 million plus royalties and up to $635 million in future payments.
Biogen and Japanese partner Eisai took a hit last March when they halted two global phase 3 trials for aducanumab, a drug that aims to slow progression of Alzheimer’s disease. But Biogen announced in October that it had changed course on the investigational drug following further data analysis and would seek the FDA’s approval after all (CenterWatch Weekly, October 28, 2019).
AstraZeneca has discontinued its large phase 3 clinical trial of Epanova, a fish oil-derived heart drug.
Hoping to imitate the successful results seen with Amarin’s Vascepa, AstraZeneca initiated the STRENGTH trial to demonstrate that Epanova was a beneficial add-on to statins for mixed dyslipidemia. The AstraZeneca trial had enrolled 13,086 patients at 675 sites across 22 countries.
With the closing of the STRENGTH trial, AstraZeneca will take a $100 million writedown on all inventories and will re-evaluate the drug’s current value of $533 million as an intangible asset.
The FDA has placed Innate Pharma’s phase 2 trial studying anti-KIR3DL2 antibody lacutamab on partial clinical hold after learning that its contract manufacturing organization (CMO) stopped production and filed for bankruptcy.
The partial clinical hold will allow investigators to continue treating existing patients in the U.S. But patient enrollment has been suspended until the company finds a new CMO, which is expected to happen before the second half of 2020.
University of Pittsburgh Medical Center’s (UPMC) venture capital arm has announced that it is setting aside $1 billion to develop new drugs and devices to treat cancer, respiratory disease, autoimmune disease and neuro-inflammation, among other conditions.
The initial focus of UPMC was on the development of immunotherapies for cancer, aging and transplantation, but the aim of the unit its capital arm is funding has now expanded its aim to reach other diseases where unmet clinical needs exist. UPMC recently invested in Werewolf Therapeutics, a biotech startup studying new immunotherapies for cancer, contributing to a $56 million Series A funding deal that included other investors.
More than half of site startups have not considered running a completely virtual trial, according to a survey by Industry Standard Research.
In its survey, Industry Standard Research, a market research firm, queried site startup experts on their stance on implementing virtual clinical trials. Approximately 54% of surveyed sites reported that they have not considered running virtual trials, compared with 20% of sites that are currently in the process of evaluating the potential of using virtual trials in the future. Only 3% of sites are currently running virtual trials.
Residents of the Thames Valley region in the UK can now search an online, interactive map for sites near them that are conducting clinical trials in the National Health Service.
Thames Valley Research map, sponsored by the National Institute for Health Research Clinical Research Network Thames Valley and South Midlands, offers users the ability to browse for nearby studies by medical specialty, keyword, postcode and study name.
Axsome Therapeutics has entered into a new agreement with Pfizer that will give it exclusive license to Pfizer’s clinical and non-clinical data as well as intellectual property rights for reboxetine, an active drug product being tested as a treatment for narcolepsy.
The data includes Pfizer’s relevant nonclinical studies, short-term trials and long-term trials that include over 5,000 patients. Axsome will also gain exclusive rights to engineer and market Pfizer’s late-stage esreboxetine (AXS-14), a U.S. product candidate for fibromyalgia treatment. Licensed data will include results of a positive phase 3 trial and positive phase 2 trial of AXS-14 in patients with fibromyalgia.
Recently, Axsome released positive results of a phase 2 trial for AXS-12, its version of narcolepsy treatment reboxetine, and the company is now initiating phase 3 trials.