Posted on 04/14/2020 11:57:49 AM PDT by SeekAndFind
Two investigators in Gilead's Phase III remdesivir trials were unsurprised at recent protocol changes. However, they said enrollment in the moderate-disease study was slow due to difficulty capturing those patients, with one also citing publicity-driven interest in two unproven malaria drugs.
Last week, Gilead Sciences made significant adjustments to the Phase III trials of its drug remdesivir in hospitalized patients with Covid-19, leading to some speculation that the company may have lowered its expectations for the drug. Two investigators in the trials weighed in on what the changes could mean, as well as some of the challenges they have encountered in enrolling patients in the trial.
Foster City, California-based Gilead launched the two randomized, but non-blinded trials – comparing remdesivir and standard treatment with standard treatment alone – last month. One was a 400-patient study in severe disease that measured the proportion of patients with normalization of fever and oxygen saturation over two weeks. The other was a 600-patient trial in moderate disease measuring the proportion of patients discharged from the hospital in the same time frame.
But on April 6, the company increased the enrollment targets to 2,400 patients for the severe-disease study and 1,600 for the moderate-disease study. In addition, it changed the primary endpoints to measure patients’ odds for clinical improvement after 14 and 11 days on a seven-point scale that ranges from the patient dying to being well enough not to require hospitalization.
A Gilead spokesperson wrote in an email that the enrollment targets were adjusted to increase access to remdesivir and provide additional data, but did not address the question of why the endpoints were changed except to say that the change was unrelated to the enrollment target increase.
“The way I interpreted that is that they wanted to provide access to remdesivir while they were analyzing the data from the first part of the study,” said Dr. Debra Poutsiaka, an infectious disease physician and lead investigator of the study for Tufts University in Boston, in a phone interview, referring to the enrollment increase. “That’s how it was conveyed to us.”
In a note to investors, RBC Capital Markets analyst Brian Abrahams gave some potential reasons for why the endpoints were changed.
“We believe the changes improve alignment to the latest understanding of COVID-19’s course and should maximize sensitivity to detect any potential treatment effect, though they also imply that – perhaps based on data the company may be observing from ongoing experience with the drug – the magnitude of benefit, if any, is likely to be modest,” Abrahams wrote. He added that it would align with the view that like other drugs in development for COVID-19, remdesivir is more likely to have incremental benefit rather than being a panacea.
But Dr. Prashant Malhotra, lead investigator of the studies for New York City-area health system Northwell Health, said in a phone interview that the new endpoints still reflect the information sought for the ones that were previously used, with measures encompassing the spectrum of the patient dying to being well enough for discharge, along with some based on “statistical finesse.”
“I wouldn’t read too much into the change,” Malhotra said.
Despite the changes, Abrahams wrote that data from the Gilead trials is still anticipated in May.
But while it’s unclear whether it would affect the timing of trial data, both interviewed investigators said enrollment in the moderate-disease trial has been slower at their centers than that in the severe-disease trial, for several reasons.
The Gilead spokesperson did not respond to a request for comment about study enrollment. Neither investigator had the current enrollment number; Poutsiaka said the last figure she saw showed the moderate-disease study was less than one-third enrolled, but that was “weeks ago.”
Poutsiaka said that it appears many patients with moderate disease are simply staying home rather than going to the hospital – hospitalization is a requirement for taking part, and the drug is administered intravenously – even if they fit the study’s criteria for enrollment. The drug is intravenous, and hospitalization is required for trial participation.
“I think that the people who come into the hospital are by definition sicker, and that’s why we’re seeing more that would qualify as severe disease in the Gilead trials,” she said.
In New York, Malhotra said, the issue is that because of the extraordinary pressure the disease is exerting on hospitals – including being asked to increase capacity by 50% – some patients who would ordinarily be admitted for observation are instead being discharged or transitioned to home observation, thereby disqualifying them for enrollment into the trials.
As of Tuesday morning, New York City, a major epicenter of the pandemic, had 106,763 cases and 7,349 deaths, with the U.S. total far surpassing half a million.
But another factor slowing enrollment in the moderate-disease trial and even the severe-disease trial, Malhotra said, is that thanks to the publicity around the antimalarial drugs hydroxychloroquine and chloroquine, patients who are admitted to the hospital are frequently put on those drugs and thus rendered ineligible for the remdesivir trials. Both studies’ exclusion criteria include participation in other clinical trials for Covid-19 treatments and “concurrent treatment with other agents with actual or possible direct acting antiviral activity against SARS-CoV-2” less than 24 hours before remdesivir dosing. Malhotra explained that patients in the remdesivir studies must have received a positive diagnosis no more than four days prior to randomization, and together with the need to be off the other drugs thus shortens the window for possible enrollment.
“It’s anecdotal, but I do think it plays a role,” Malhotra said, adding that he had heard similar accounts from investigators at other centers.
Consenting patients has also been a challenge due to the need to avoid direct contact with them and concerns that the traditional paper forms could act as fomites that could spread the virus. Poutsiaka said Tufts has adopted a completely remote process involving the investigator, an impartial witness, the patient and any family members and friends getting on the phone to coordinate consent, though the logistics of a phone call with four or five people are the “most difficult part” of the study. Northwell has adopted workarounds like calling patients’ legal representatives.
Kind of like asking is the water at the oasis hampering the fig/date business...
heard this stuff costs $1000 a dose
The people’s automobiles are hindering the expansion of bus routes.
8 billion people on the planet, and they can’t find anyone for their trials because of HCQ- Yeah okie dokie then-
heard this stuff costs $1000 a dose
5 days of the HCQ therapy costs $20.00.
Why let the fox into the hen house?
It just burns Big Pharma that the treatment for potentially the biggest money maker disease in history was developed decades ago. The patent is even expired. Who can make money on a generic 50 cent dose of miracle drug?
RE: heard this stuff costs $1000 a dose
Yep, that’s the deal. The mentality seems to be — the more expensive something is, the more “proven” it will have been.
WHY? Because it shall have gone through the very expensive PHASED trials the FDA requires before approval ( which of course, requires the maker to spend millions ).
The reason the China Virus totals in NYC are looking better is because they are now allowing the use of HCQ. In fact it is being used all across the country now and in many places around the world. Reports so far are 95+% positive regarding the efficacy of the “Trump Drugs” and this is why you seldom hear anything from the Liberal media about it.
MY guess is when they put together enough statistics showing how positive the drug can be they will use it when the President announces it is time for us to go back to work.
Calvin Coolidge-”...the chief business of the American people is business. They are profoundly concerned with producing, buying, selling, investing and prospering in the world.”
Let’s get to it.
Well, I believe the subjects for the trial have to already have the China Virus.
If you had it and had a choice between the HCL and the Remdesiver which would you choose?
RE: Reports so far are 95+% positive regarding the efficacy of the “Trump Drugs” and this is why you seldom hear anything from the Liberal media about it.
I’m not sure where you are getting that 95+% from.
I’ll grant that this 95+% figure came from non-randomized trials and administration by Dr. Didier Raoult of France and Dr. Vladimir Zelenko of upstate New York. NYC doctor, Dr. William Grace also gave us a figure close to that in his own practice. So did Dr. Stephen Smith of NJ.
However, I have been waiting in vain on the other hand for New York state to give us their numbers, as well as other hospitals around the country.
If you have the sources, we would all be glad to learn about them.
“...Foster City, California-based Gilead launched the two randomized, but non-blinded trials – comparing remdesivir and standard treatment with standard treatment alone – last month...”
*******************************************************
Hmmmm.... “randomized but NON-BLINDED trials” for Gilead’s drug. But for the Hydroxychloroquine cocktail treatment they insist upon randomized DOUBLE BLIND PLACEBO CONTROLLED trials - which are being conducted now. Interesting double standard.
Anyhow, I’m glad at least the Hydroxychloroquine cocktail regimen is getting the “gold standard” trial treatment.
the problem is that remdesivir is not very effective.
“Of the 53 patients whose data were analyzed,
22 were in the United States, 22 in Europe or Canada,
and 9 in Japan,”
New England Journal of Medicine.
“In this cohort of patients hospitalized for severe
Covid-19 who were treated with compassionate-use remdesivir,
clinical improvement was observed in 36 of 53 patients
(68%).”
https://www.foxnews.com/scienc…ng-early-promise-research
so tough cookies for Gilead.
people can take the known cure,
or the useless unproven vaccine of Gates,
or the not effective alternative.
easy choice.
“If you have the sources, we would all be glad to learn about them.”
Of course I don’t have them. There aren’t any besides the ones you mentioned and a few single anecdotal instances such as the Democrat Congressman/woman from Mich and a few others.
I expect the numbers from NY will be overwhelmingly positive but will be spun by the media as inconclusive because the tests didn’t go on long enough or they didn’t use a control group (I never did hear they were doing that anyway).
oh i thought at first it was for a vaccine trial- (Didn’t read through hte article=- per usual- my bad) which if so then that would have meant getting it before getting hte virus- but the drug here is treatment for the virus, not vaccine- so yeah, you’re right-
“millions”???
The pharma industry passed that benchmark decades ago.
Today it costs 2,500 millions to bring a new drug to market. That is $2.5 BILLION.
It takes one successful drug to make up for the other 30 drugs that didn’t become commercial successes.
In R&D, you typically see 1,000 ideas in the basic research hopper, 100 get to the applied research hopper, 10 get to serious development and ONE emerges as a commercial product — and that ONE may or may not succeed in the market.
People just do not understand how the product development funnel works.
that’s down from a $100,000 treatment regimen. A Bargain. /s
The MSM is pushing this and not HCQ because they see Humira sized $ signs in their dying future.
Poor Bill Gates may not become a Trillionaire.
A - Enroll in Gilead's test and face a 50% chance of receiving a placebo.
B - Get a scrip for the HCQ/Z-pack combo knowing you have a 95% chance of feeling better in a matter of hours.
Are you going to whine about the lack of a double-blind study of the HCQ?
Maybe the right headline should be “Is Hydroxycholoroquine Endangering Big Pharma Gravy Train?”
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