Market Place
‘FDA compromised standards to get Bayer’s chloroquine’; HCQ study shows no benefits, higher deaths in study
This week, Phispers brings you updates on remdesivir, hydroxychloroquine (HCQ) and chloroquine — drugs being touted as treatments for Covid-19.
While Gilead’s remdesivir, which made news for a study being undertaken at a Chicago hospital, shows promise, it needs rigorous trials to be recommended as treatment for the infection.
Novartis is conducting a randomized, double-blind placebo-controlled trial on HCQ, even as a nationwide study undertaken in the US with 368 patients on the drug, with or without azithromycin, reveals more deaths among Covid patients that were given HCQ as opposed to those on standard care.
Moderna Inc received US$ 483 million in funding from BARDA to accelerate the development of its experimental vaccine.
While this was happening, the director of BARDA Rick Bright was abruptly dismissed and moved to NIH.
GE and Ford Motors signed a US$ 336 million deal under the Defence Production Act of the US to produce 50,000 ventilators.
An exposé by journalist Katherine Eban reveals FDA compromised on quality standards to get Bayer’s donation of three million tablets of chloroquine.
In the US, the NIH published guidelines on treatments for Covid-19 and said no drug has so far proven effective.
And even as India relaxed export of APIs, paracetamol formulations and HCQ, its supply chain got affected due to multiple plant shutdowns over the Covid scare.
Eban’s exposé points to FDA compromising on quality standards to
get Bayer’s chloroquine
Journalist Katherine Eban, whose book titled ‘Bottle of Lies’ had made headlines and shook the pharmaceutical industry last year is back with another investigation. This time, Eban has investigated on how FDA may have dropped its standards far too much in its search for chloroquine to fight Covid-19.
According to a Reuters report, authored by Eban, Bayer AG made a hefty donation of three million tablets of the drug, called Resochin (chloroquine), two days after US President Donald Trump first touted chloroquine drugs as a “gamechanger” in the fight against Covid-19. After a brief period of testing, its use in the US was approved on an emergency basis.
The report says Keagan Lenihan, chief of staff of the US Food and Drug Administration (FDA), had cautioned that “three to four days” of testing would be needed to test the drug.
“Potentially serious issues with product so let’s be careful when we take that win,” Lenihan had written in an email exchange to federal health officials.
Three US government sources familiar with the matter told Reuters that there is reason to be concerned about the quality of Resochin and its manufacturers, who are situated in India and Pakistan. These plants have never been registered with, or inspected by, the FDA.
Some chloroquine drugs were already approved by the FDA before the pandemic as antimalarial medications, a process that required plant inspections. However, Resochin was not approved.
“Although some rules can be waived in an emergency, the FDA dropped its quality-control standards too far as it scoured the world for scarce supplies of chloroquine drugs,” the report says.
In fact, Pakistani regulators, who inspected Bayer’s Resochin plant in Karachi in 2015, found a “gross failure” in manufacturing processes there. In the case of the Indian plant situated in Indore, the FDA has never screened it.
Bayer, however, had said the FDA had tested Resochin “and found it to be of appropriate quality for release to the (stockpile) for emergency use.”
On its website, Bayer said doctors consider Resochin a promising treatment for seriously ill coronavirus patients. “New data from initial preclinical and evolving clinical research conducted in China, while limited, shows potential for the use of Resochin in treating patients with Covid-19 infection,” the Bayer statement said.
Head of BARDA, who resisted broad use of
chloroquine and HCQ, makes sudden exit
The director of the Biomedical Advanced Research and Development Authority (BARDA) and one of America’s leading vaccine development expert Rick Bright is no longer heading the organization. Bright’s exit has come at a time when the novel coronavirus epidemic is at its peak.
A CNN report said Bright was abruptly dismissed from his post in part because he resisted efforts to widen the availability of a coronavirus treatment pushed by the US President Donald Trump.
“I believe this transfer was in response to my insistence that the government invest the billions of dollars allocated by Congress to address the Covid-19 pandemic into safe and scientifically vetted solutions, and not in drugs, vaccines and other technologies that lack scientific merit,” Bright said.
"I limited the broad use of chloroquine and hydroxychloroquine, promoted by the Administration as a panacea, but which clearly lack scientific merit. While I am prepared to look at all options and to think "outside the box" for effective treatments, I rightly resisted efforts to provide an unproven drug on demand to the American public.”
“I am speaking out because to combat this deadly virus, science — not politics or cronyism — has to lead the way.” Bright had been the head of BARDA since 2016. According to a US Department of Health and Human Services (HHS) spokesperson, Bright will begin working out of the National Institutes of Health (NIH).
BARDA invests in drugs, devices, and other technologies that help address infectious disease outbreaks. The US Congress had more than tripled BARDA’s budget in the most recent coronavirus stimulus package. Gary Disbrow, Bright’s former deputy at BARDA, will now serve as its acting director.
HCQ study shows no
benefits, higher deaths in study on 368 male veterans in US
Last week, we had carried a report on how various studies across the world had raised questions on the efficacy of hydroxychloroquine (HCQ) — that had been touted by US President Donald Trump as the game-changer.
This week, there is a report on a nationwide study undertaken in the US with 368 patients on HCQ, used with or without azithromycin for Covid-19. According to researchers, there were more deaths among those given HCQ versus standard care.
The study was posted on an online site for researchers and has not been reviewed by other scientists. Grants from the National Institutes of Health (NIH) and the University of Virginia paid for the work.
Researchers analyzed medical records of 368 male veterans hospitalized with Covid-19 infection at Veterans Health Administration medical centers who died or were discharged by April 11.
About 28 percent who were given HCQ plus usual care died, as opposed to 11 percent of those getting routine care alone. About 22 percent of those getting the drug plus azithromycin died too, but the difference between that group and usual care was not considered large enough to rule out other factors that could have affected survival. HCQ made no difference in the need for a breathing machine, either.
Researchers did not track side effects, but noted that HCQ might have damaged other organs. The drug has been known to have potentially serious side effects, including altering the heartbeat in a way that could lead to sudden death.
“These findings highlight the importance of awaiting the results of ongoing prospective, randomized, controlled studies before widespread adoption of these drugs,” the study said.
Remdesivir shows promise
against Covid-19 in short study, but needs rigorous trials
On April 15, there was news that Gilead Sciences’ trial of its Ebola drug remdesivir being undertaken in China in patients with milder form of Covid-19 had to be suspended, as no eligible patients could be recruited. This was the second such suspension in China, after the country had to halt enrollment of severe Covid-19 patients for a trial on remdesivir due to lack of patients.
Post this news, Gilead’s shares were down 3 percent on Wednesday. The following day, STAT News carried a report that a study being undertaken in a Chicago hospital treating severe Covid-19 patients with remdesivir in a closely watched clinical trial is seeing rapid recoveries.
“The best news is that most of our patients have already been discharged, which is great. We’ve only had two patients perish,” Kathleen Mullane, the University of Chicago infectious disease specialist overseeing the remdesivir studies for the hospital, told STAT News in a video that was recorded.
The University of Chicago Medicine had recruited 125 people with Covid-19 into Gilead’s two Phase 3 clinical trials. Of those, 113 had severe disease.
Post this news, Gilead’s shares surged 16 percent. On Friday, a congressman sought a US Securities and Exchange Commission (SEC) investigation into the leak of the video.
Interestingly, the University of Chicago is one of 152 locations participating in Gilead’s trial involving severe Covid-19 patients. This means it is “single arm” and does not measure the drug against a matched group of patients treated with a placebo.
In a statement, Gilead said: “The totality of the data need to be analyzed in order to draw any conclusions from the trial.” Gilead expects results from its Phase 3 study in patients with severe Covid-19 by the end of this month, and additional data from other studies in May.
Most of the studies we read about on drugs like hydroxychloroquine (HCQ) and remdesivir are short studies that are not randomized (for instance, some compared patients who agreed to take the drug to those who didn’t) and not blinded (doctors and patients knew who got which drug). Such studies have shown conflicting results. Most such studies also did not include comparisons to a control group (patients who do not receive the drug or treatment being investigated), which is critical in any clinical trial.
Last week, The New England Journal of Medicine published an analysis showing that two-thirds of a small group of severely ill Covid-19 patients saw their condition improve after treatment with remdesivir. Calling the findings “hopeful”, the paper’s author cautioned it is difficult to interpret the results since they do not include comparison to a control group, the patient numbers were small, the details being disclosed were limited, and the follow-up time was relatively short.
Novartis conducts randomized, controlled study on HCQ: Novartis is conducting a 450-person study to determine if HCQ can effectively treat Covid-19. The study will be a randomized, double-blind placebo-controlled study, the medical gold standard in which patients will be assigned one of three options: HCQ, the combination of HCQ and the antibiotic azithromycin, or placebo.
John Tsai, the chief medical officer of Novartis said the company wanted to embark on a rigorous, scientifically led approach to find out whether the use of HCQ can help patients with Covid-19.
The study will not include patients who are very sick and on ventilators. It will include adults who are hospitalized and are in what doctors call the moderate-to-severe population, and may need oxygen supplementation.
NIH publishes guideline on treatments; says no drug proven
effective for Covid-19
A panel of US physicians, statisticians, and other experts have developed treatment guidelines for Covid-19. These guidelines, intended for healthcare providers, are based on published and preliminary data and the clinical expertise of the panelists, many of whom are frontline clinicians caring for patients during the rapidly evolving pandemic in the US.
Posted online on the NIH website, the guidelines will be updated often as new data emerges.
The guidelines consider two broad categories of therapies — antivirals; and host modifiers and immune-based therapies.
On treatment guidelines, the NIH states that at present, no drug has been proven to be safe and effective for treating Covid-19. There are no US Food and Drug Administration (FDA)-approved drugs specifically to treat patients with Covid-19.
The NIH stated there is insufficient clinical data to recommend either for or against using chloroquine or hydroxychloroquine (HCQ) for the treatment of Covid-19. The NIH made the same statement over the use of investigational antiviral drug — remdesivir — as here too, the clinical data available is insufficient to arrive at a conclusion.
The NIH also said that there is insufficient clinical data to recommend either for or against the use of convalescent plasma or hyperimmune immunoglobulin for the treatment of Covid-19.
Moderna’s vaccine gets US$ 483 million in grant; Oxford tests vaccine “at risk”
Moderna Inc has been in news for its experimental vaccine for the novel coronavirus, which has reached early-stage of human trials. Last week, the company received US$ 483 million contract from the Biomedical Advanced Research and Development Authority (BARDA) to accelerate the development of this vaccine.
This funding would support the vaccine’s clinical development program, as well as scale-up the manufacture of the vaccine candidate — mRNA-1273 — in 2020. Moderna plans to hire up to 150 new team members in the United States this year to support the ramp-up.
The early-stage trial for this experimental vaccine is being conducted by the US National Institutes of Health (NIH). Moderna expects to begin mid-stage trial in the second quarter and depending on the data emerging out of these trials, late-stage study could begin by fall of 2020.
Meanwhile, Sanofi CEO Paul Hudson has said if the company’s coronavirus vaccine works, it can produce up to 600 million doses next year. “We believe we’re one of the few companies who will be able to make a vaccine at a huge scale,” Hudson said.
Recently, Sanofi and GSK had announced they have entered into an agreement to jointly create a Covid-19 vaccine by the end of next year. The companies plan to start clinical trials in the second half of 2020 and, if successful, make it available to the public by the second half of 2021.
UK tests vaccine “at risk”: Scientists at the Oxford University said they were recruiting volunteers for early stage —Phase 1 —human trials of their experimental vaccine, and large-scale production capacity was being put in place “at risk”.
This means the shots will be produced in large numbers at risk of being useless if trials show they do not work. The Oxford University’s experimental product, called “ChAdOx1 nCoV-19”, is a recombinant viral vector vaccine.
India relaxes export of paracetamol formulations even as plants shut down due to Covid
scare
In March, the Indian government had restricted the exports of 13 APIs along with some of their finished formulations. In early April, the restriction on the drug exports was lifted on all the APIs along with their finished formulations, except paracetamol and hydroxychloroquine (HCQ).
Earlier this month, India partially lifted the ban on the export of HCQ and paracetamol. And last week, India moved formulations of paracetamol from restricted to free for export with immediate effect, though paracetamol APIs remain restricted for export.
India manufactures around 70 per cent of the world’s HCQ and is also a leading manufacturer of paracetamol. However, things do not look as good on the supply chain front.
Baddi (in Himachal Pradesh), a key manufacturing location for finished pharmaceutical exports, has been hit by the novel coronavirus and lots of units have been closed. Moreover, Jubilant Generics Limited, a key manufacturer of APIs like azithromycin dihydrate and azithromycin monohydrate — important drugs being recommended to fight Covid-19 — had to shut its Nanjangud plant near Mysuru as 49 employees at the facility tested positive for the virus.
According to a news report published in The Economic Times, 50 drug manufacturing facilities have shuttered their operations in Baddi while others are operating at significantly reduced capacities after the region was declared a containment zone. The list includes plants of major pharma companies such as Wockhardt, USV Pharma and Sun Pharmaceuticals.
Meanwhile, Jubilant has said none of its employees who had tested positive for novel coronavirus had travel history to China, refuting the claim made by a Karnataka government minister.
GE, Ford sign US$ 336 million federal contract to make ventilators
With the US recording over 850,000 confirmed cases of Covid-19 since the start of the pandemic, and over 47,000 deaths, companies like General Electric and Ford Motors have said they will produce 50,000 ventilators for the US government under the Defense Production Act for US$ 336 million.
Beginning next week, the companies are expected to produce the life-saving devices at a facility in Michigan. Each ventilator would cost US$ 6,720 — that’s nearly US$ 10,000 below a previous federal contract for 30,000 ventilators at US$ 489.4 million, or about US$ 16,300 per unit.
Ford and GE Healthcare will leverage the design of Airon Corp’s FDA-cleared ventilator. According to the HHS, the companies are expected to produce all the ventilators by July 13.
There are various manufacturers that have got into the manufacturing of ventilators to meet the shortfall of these life-saving devices. In India, medical equipment manufacturers have roped in companies like Maruti, Mahindra & Mahindra and Tata Motors to manufacture ventilators. Similarly, factories in China are working round-the-clock to manufacture ventilators for countries like Italy and the US.
The PharmaCompass Newsletter – Sign Up, Stay Ahead
Feedback, help us to improve. Click here
Image Credit : #Phisper Infographic by SCORR MARKETING & PharmaCompass is licensed under CC BY 2.0
“ The article is based on the information available in public and which the author believes to be true. The author is not disseminating any information, which the author believes or knows, is confidential or in conflict with the privacy of any person. The views expressed or information supplied through this article is mere opinion and observation of the author. The author does not intend to defame, insult or, cause loss or damage to anyone, in any manner, through this article.”
