Target to $11 from $21
Tuesday, September 13, 2022
FDA Clears Akouos' Gene Therapy Trial For Genetic Form Of Hearing Loss
The FDA has signed off Akouos Inc's (NASDAQ: AKUS) Investigational New Drug application to initiate a Phase 1/2 trial of AK-OTOF, gene therapy for otoferlin gene (OTOF)-mediated hearing loss.
OTOF-mediated hearing loss is a form of sensorineural hearing loss caused by mutations in the otoferlin gene, which encodes otoferlin. This protein enables the inner hair cells of the cochlea to release neurotransmitter vesicles in response to stimulation by sound to activate auditory neurons.
The Phase 1/2 trial is designed to evaluate the safety and tolerability of escalating doses of AK-OTOF administered unilaterally to trial participants with OTOF-mediated hearing loss.
It will also assess efficacy through clinical measures such as ABR, an objective, clinically accepted endpoint.
Nonclinical data demonstrated that AK-OTOF in Otof knockout mice results in durable expression of human otoferlin protein sufficient for sustained restoration of auditory function.
In both mice and non-human primates, AK-OTOF was systemically and locally well tolerated, and no adverse effects were observed.
The company plans to provide an update on clinical trial initiation activities later this year.
89bio up after conference session
89Bio Inc. shares rose 34%, to $6.68, after Chief Executive Rohan Palekar discussed the progress of its lead drug candidate Monday during an H.C. Wainwright conference.
Mr. Palekar detailed the "broad metabolic benefits" and favorable clinical trial results for pegozafermin. The drug is being developed for non-alcoholic steatohepatitis and severe hypertriglyceridemia.
89bio, Inc. (ETNB) shares are trading more than 36 percent on Tuesday morning continuing an uptrend since the company reported positive results from ENTRIGUE Phase 2 trial of Pegozafermin in patients with severe Hypertriglyceridemia.
https://www.marketwatch.com/story/89bio-up-after-conference-presentation-271663090966
Insiders Are Buying Up Comera Life Sciences
Shares of Comera Life Sciences (NASDAQ:CMRA) are up by over 30% following a flurry of insider purchases. As the name suggests, Comera is a life sciences company that seeks to improve traditional intravenous injections through its SQore platform. SQore tackles formulation challenges through “novel, patented excipients” that may improve the ease of administration. Comera partners with pharmaceutical and biotechnology companies to help improve the delivery of medicines and to develop a portfolio of proprietary SQore therapeutics.
Before September, no insiders had purchased shares of CMRA stock in 2022. Now, even the CEO is buying shares. Let’s get into the details.
CFO Michael Campbell started off the flurry of insider purchases. On Sept. 8, he purchased 25,000 shares at an average price of $2.07. Before the purchase, he owned zero shares of his company. The next day, Chairman and CEO Jeffrey Hackman purchased 47,600 shares at an average price of $2.06. Like Campbell, Hackman owned zero shares before the purchase. Then, on Sept. 12, Director James Sherblom picked up 50,000 shares at an average price of $2.03. After the purchase, Sherblom now owns a total of 371,163 shares.
In addition, it should be noted that none of the above three purchases were enacted via a prearranged 10b5-1 trading plan. Insiders often buy or sell shares of their own company using this plan in order to avoid accusations of insider trading. It’s unclear the exact reason for the purchases, although insiders only buy shares of their own company for one reason: they believe the price will go up.
On Aug. 31, the company announced that it had entered into a purchase agreement with Arena Business Solutions. Pending U.S. Securities and Exchange Commission (SEC) approval, Comera will have the right to sell Arena up to $15 million shares over a three year period. Hackman added: “Strengthening our balance sheet will help us achieve our strategic objectives in the near-term, and we are grateful for Arena’s commitment to Comera’s success.”
Arena will also have an option to purchase an additional $15 million to $30 million of shares. Comera will use the proceeds toward “working capital and general corporate purposes.”
https://investorplace.com/2022/09/insiders-are-buying-up-comera-life-sciences-cmra-stock-heres-why/
Akero Wows Investors With Unexpected Win For Hepatitis Treatment
Akero Therapeutics (AKRO) wowed investors Tuesday with midstage test results for a hepatitis treatment, and the biotech stock skyrocketed by triple digits.
In morning trades on today's stock market, Akero shares soared 115.4% near 26.40. Shares of 89bio (ETNB), another NASH drugmaker, rocketed 35.2% near 6.70.
Akero tested a treatment for nonalcoholic steatohepatitis, or NASH. NASH causes fat to build up in the liver, leading to inflammation and scarring called fibrosis.
Patients received Akero's drug for six months. Depending on the dosage, 39%-41% of patients experienced improvement in fibrosis while their NASH symptoms remained in check. Just 20% of placebo recipients had the same result.
"We believe today's results from the (study called) Harmony are an important milestone not only for Akero, but for the entire NASH community," Akero Chief Executive Andrew Cheng said in a written statement. "As the fastest growing cause of liver transplantation and liver cancer in the U.S. and Europe, NASH represents a substantial and growing health burden."
Biotech Stock: A Tricky Bar In NASH
Akero's news helped the biotech stock open at its highest point since June 2021.
The company tested its drug in patients with stage 2-3 fibrosis. Fibrosis is measured on a scale of 1-4. Today, there is no approved NASH treatment because the bar is tricky. A drug must either lead to a one-stage improvement in fibrosis without causing worse NASH symptoms, or it must resolve the symptoms of NASH without leading to worse fibrosis.
In Akero's study, 39%-41% of patients who received the drug — dubbed efruxifermin — experienced at least one-stage improvement in fibrosis and no worsening in NASH symptoms. In comparison, just 20% of placebo recipients had the same result. Also bullish for the biotech stock, 47%-76% of patients achieved NASH resolution without worsened fibrosis, vs. just 15% in the placebo group.
Further, 29%-41% of patients hit both goals: improved fibrosis and NASH resolution.
The results suggest efruxifermin "has the potential to treat the core facets of NASH," Dr. Stephen Harrison, medical director of Pinnacle Clinical Research, said in a written statement. Harrison was the primary investigator for the study.
The most frequent side effects were diarrhea, nausea, increased appetite and more frequent bowel movements. Five efruxifermin recipients dropped out of the study due to side effects vs. none of the placebo recipients. One patient reported a severe case of esophageal swelling. But that patient also had a history of gastroesophageal reflux disease, Akero said.
Rival Gets A Boost Too
The results also bolstered smaller biotech stock 89bio, which is working on a similar approach to NASH. 89bio is expected to have the results from its Phase 2 study in the first quarter, RBC Capital Markets analyst Brian Abrahams said in a note to clients.
Abrahams sees a multibillion-dollar opportunity in NASH treatment. He acknowledged "commercial and regulatory uncertainties in the space," but said safety and broad metabolic benefits of 89bio's and Akero's drugs should pave the way to U.S. approvals.
Medical journals broaden inquiry into potential heart research misconduct
Three medical journals recently launched independent investigations of possible data manipulation in heart studies led by Temple University researchers, Reuters has learned, adding new scrutiny to a misconduct inquiry by the university and the U.S. government.
The Journal of Molecular and Cellular Cardiology and the Journal of Biological Chemistry are investigating five papers authored by Temple scientists, the journals told Reuters.
A third journal owned by the Journal of American College of Cardiology (JACC), last month retracted https://www.jacc.org/doi/10.1016/j.jacbts.2019.10.006 a paper by Temple researchers on its website after determining that there was evidence of data manipulation. The retracted paper had originally concluded that the widely-used blood thinner, Xarelto, could have a healing effect on hearts.
“We are committed to preserving the integrity of the scholarly record,” Elsevier, which owns the Journal of Molecular and Cellular Cardiology and publishes the two other journals on behalf of medical societies, said in a statement to Reuters.
Philadelphia-based Temple began its own inquiry in September 2020 at the request of the U.S. Office of Research Integrity (ORI), which oversees misconduct investigations into federally funded research, according to a lawsuit filed by one of the researchers.
The Temple investigation involves 15 papers published between 2008 and 2020 and supported by grants from the U.S. National Institutes of Health, according to the court records. Nine of the studies were supervised by Abdel Karim Sabri, a professor at Temple’s Cardiovascular Research Center.
His colleague Steven Houser, senior associate dean of research at Temple and former president of the American Heart Association, is listed as an author on five studies supervised by Sabri. Houser was also involved in four additional papers under scrutiny.
Houser sued in federal court last year to stop the university’s inquiry, saying Temple sought to discredit him and steal his discoveries.
Houser “has not engaged in scientific or other misconduct, has not falsified data, and has not participated in any bad acts with any other scientist or academic,” Houser’s lawyer, Christopher Ezold, said in a statement to Reuters. Houser helped review and edit the text portions of the Sabri-supervised studies and did not provide or analyze the data, Ezold said.
A Temple spokesperson said the university is “aware of the allegations and is reviewing them.” He would not comment further or discuss interactions with medical journals. ORI also declined comment. Sabri and Houser did not respond to questions.
Several research experts said that Houser, as one of multiple co-authors, cannot be assumed to be involved in potential misconduct. The ultimate responsibility for a study usually lies with the supervising scientist and any researcher who contributed the specific data under scrutiny.
EXPRESSION OF CONCERN
The probes highlight concerns over potential fabrication in medical research and the federal funds supporting it. A Reuters investigation https://www.reuters.com/investigates/special-report/health-hearts-stem-cells/ published in June found that the NIH spent hundreds of millions of dollars on heart stem cell research despite fraud allegations against several leading scientists in the field.
The Temple inquiry also reveals a lack of consensus within the scientific community over how such concerns should be communicated, to prevent potentially bad science from informing future work and funding, according to half a dozen research experts interviewed by Reuters.
Temple did not notify the medical journals that it was conducting an inquiry at the request of the U.S. government agency, the journals told Reuters. They said that they began their inquiries independently.
Xarelto’s manufacturer, the Janssen Pharmaceuticals division of Johnson & Johnson, also told Reuters the supervising researchers at Temple did not notify the company about the investigation or the retraction by the JACC journal, though two of its employees were listed as co-authors on the paper. Janssen said their contribution to the paper was not questioned in the retraction.
In some misconduct inquiries, universities have notified scientific journals that an investigation is underway. That has allowed journals to issue an “expression of concern” about specific studies, telling readers that there may be reason to question the results. If there is a finding of data manipulation, the journals would be expected to retract the paper.
None of the journals that published the papers under scrutiny by Temple have issued expressions of concern. They would not comment to Reuters as to why they decided not to.
“It’s murky because of a lack of resources for these investigations, there’s no standardization worldwide,” said Arthur Caplan, head of medical ethics at New York University’s Grossman School of Medicine.
Other journals are not scrutinizing the Temple researchers’ work. Five papers flagged by ORI were published in the AHA journals Circulation, Circulation: Heart Failure, and Circulation Research, where Houser is a senior advisory editor.
The AHA said it had not been notified by the U.S. agency or by Temple about their inquiry, and that it does not view itself as responsible for investigating further. The AHA said it had issued a correction of data on one paper at the authors’ request. The paper was the sole study under scrutiny that listed Houser as supervising researcher.
“The American Heart Association is not a regulatory body or agency,” the AHA said in a statement to Reuters.
FEDERAL FUNDING
Researchers and their institutions can be forced to return federal funding that supported work tainted by data manipulation.
Houser has received nearly $40 million in NIH funding and Sabri has received nearly $10 million since 2000, according to a Reuters analysis of NIH grants. Houser’s lawyer said that none of his NIH funding supported the papers supervised by Sabri.
The JACC journal said in its retraction of the Xarelto research that it launched its investigation after receiving a complaint from a reader. In response, the researchers issued a correction of some image data in the paper, which was supervised by Sabri and which listed Houser as an author.
However, the journal said that the correction raised further concerns, prompting it to hire an unidentified outside expert to review them.
According to the retraction notice, the expert evaluation found evidence of manipulation in seven images using a technique known as Western blot, which determines concentrations of a specific protein in cells or tissues under different experimental conditions. As a result, the journal said its ethics board voted to retract the paper.
NIH, ORI and Temple declined to comment on whether Temple would be required to return any federal funding of the work retracted by the JACC publication.
Dems pressured the FDA to delay COVID vaccine to hurt Trump
For every week we didn’t have a COVID-19 vaccine, more people died, more children were kept out of school, and more damage was done to society.
Yet it’s become increasingly clear that the FDA put the brakes on the vaccine at the 11th hour, delaying its authorization because Democrats — worried it would help Donald Trump’s 2020 re-election prospects — undermined public confidence in the vaccine development efforts.
We may never know how much damage was done in the name of politics. But one victim is clear: Americans’ trust in their government and public health experts.
Democrats are trying to deflect blame for this scandal by claiming the inverse: That the Trump administration undermined public trust by irresponsibly trying to “rush” the vaccine for political gain.
Last month, in a Congressional report provocatively titled “A ‘Knife Fight’ with the FDA: The Trump White House’s Relentless Attacks on FDA’s Coronavirus Response,” the House Select Subcommittee on the Coronavirus Crisis alleged that Trump administration officials “blocked FDA from issuing guidance on coronavirus vaccine authorizations for weeks in an attempt to ensure that the first vaccine could be authorized before the 2020 presidential election.”
It claims that the administration’s actions “resulted in damaging consequences for the coronavirus response” by undermining public confidence in the vaccine.
But the report, and the testimony of former FDA commissioner Dr. Stephen Hahn to the commission on which it is based, reveal these assertions are misleading, politically motivated distortions.
In reality, it was Trump opponents who undermined public confidence resulting in new FDA guidelines that delayed vaccine availability and likely cost lives.
Here are the facts:
We know from interviews that vaccine trials were proceeding faster than anticipated and that an announcement about vaccine efficacy was possible by the end of October 2020 with authorization soon to follow.
On Sept. 9, 2020, Pfizer CEO Albert Bourla announced on the “Today Show” that Pfizer had joined a pledge with other pharmaceutical companies to follow FDA guidance and to only request a vaccine emergency use authorization after demonstrating safety and efficacy through a Phase 3 clinical study. Pfizer’s trials were moving faster than expected and he predicted the company would likely have results by the end of October.
Five days later, on “Face the Nation,” Bourla said that there was more than a 60% chance Pfizer would know results by the end of October.
That didn’t happen. Instead, on November 9, six days after the presidential election, Pfizer announced that its COVID-19 vaccine candidate was 90% effective. Eleven days later it filed a vaccine emergency use authorization request — the first in the U.S. — that was granted on December 11.
The delay followed a curious FDA decision to toughen its standards for COVID vaccine safety review (effectiveness guidelines were unchanged). The agency would now require a median follow-up of 60 days after the vaccine shots to check for adverse side effects.
The House report fails to mention that these new guidelines—submitted to the White House and HSS on September 21 — revised earlier June 2020 guidelines that stated the “safety evaluation of COVID-19 vaccines . . . should be no different than for other preventive vaccines for infectious diseases.”
In his book “Warp Speed,” Paul Mango, former HHS Deputy Chief of Staff for Policy who was intimately involved with the vaccine effort, reports that vaccine developers understood the earlier guidance to mean trials would only be required to monitor for adverse events for, at most, 42 days after the second dose.
So why did the FDA add 18 days to the side effects check?
Officials at the White House had the same question. FDA commissioner Hahn reported push-back from administration officials with “questions about whether the 60-day meeting [sic] follow-up in particular was appropriate given the urgency of the situation.” He repeatedly said the interactions were “cordial” and not “contentious.”
The report insinuates that administration officials who questioned the need for an additional 18 days of follow-up were solely interested in the political goal of getting a vaccine out before the election. Yet the report admits that, “When asked if President Trump ever expressed a specific desire to have a vaccine approved before the election, Dr. Hahn replied in the negative.”
In fact, when the majority (Democratic) counsel repeatedly asked if President Trump or others “express[ed] a desire to have the vaccines available before Election Day?” Hahn responded, “President Trump expressed his desire for these to be approved as quickly as possible to save lives” and that “There was no one at the White House who contacted me and expressed a desire for a specific timeframe for emergency use authorization.”
Paul Mango echoes this in “Warp Speed.” He attended every briefing of the Warp Speed team in the Oval Office and never heard “President Trump ask the team to have a vaccine prior to Election Day.”
Dr. Hahn acknowledged that administration officials “across the board” were interested in speeding up the development and approval of vaccines. Yet he viewed that as normal: “I mean, we were in a public health emergency and it was totally appropriate to ask the question, what can you do to speed this up to get lifesaving treatments, vaccines, et cetera, into the hands of people?”
Hahn also made it clear that administration officials continued to press him on speeding up vaccine authorization well after the election which undermines the contention that all the administration cared about was pre-election approval.
After the new guidelines, Bourla wrote in an open letter on the Pfizer website, that, “we may know whether or not our vaccine is effective by the end of October,” but that because the FDA was now requiring 60 days of safety data, they did not expect to be able to file for an emergency use authorization until the third week of November.
It is clear that delayed EUA submission resulting from the new FDA safety guidelines was consequential.
Both daily cases and daily deaths started to rise in mid-October 2020 and peaked in mid-January 2021. The 7-day moving average of COVID deaths reached the highest level during the entire pandemic on January 13, 2021. Had vaccines been authorized weeks earlier — during a period when COVID deaths averaged thousands per day — tens of thousands fewer would have died.
Why did the FDA change its vaccine authorization guideline?
Hahn indicated that FDA began to formulate new guidelines during the summer to counteract public concerns that the agency “might be cutting corners and that it might not be safe or effective.”
In “Warp Speed,” Paul Mango confirms that Dr. Peter Marks, Director of the FDA Center for Biologics Evaluation and Research, which approves vaccines, told him the FDA was concerned about vaccine hesitancy resulting from comments questioning the speed of vaccine development. Marks told him new guidance was “essential to shoring up vaccine confidence.”
The House report claims that President Trump’s public comments that “[i]t wouldn’t hurt” to have a vaccine available before election day was responsible for the decrease in public confidence. But Hahn downplayed the impact of Trump’s tweets. “It was . . . the entire set of circumstances.” he said, including “A presidential election, bitter divisions in the country and in Congress” and according to Hahn, but unmentioned by the report, “The people who said they wouldn’t take the vaccine if it was authorized under President Trump’s watch.”
Those people were candidates Biden and Harris, who, along with their political, scientific and media allies, repeatedly criticized the vaccine development under President Trump and impugned the FDA’s independence and integrity.
Hahn believed statements by candidate Biden such as “If and when the vaccine comes, it’s not likely to go through all the tests that need to be done” and by candidate Harris that she wouldn’t take a vaccine promoted by Trump, unfairly cast doubt on the FDA. The Biden/Harris campaign website explicitly maligned Hahn and the FDA.
Senate Democratic leader Chuck Schumer also questioned the safety of the vaccines then in development and the FDA’s integrity, claiming the agency was succumbing to Trump administration pressure. He was joined by then New York Governor and media darling, Andrew Cuomo, who said he would not trust a vaccine approved by the FDA and federal government.
Biden medical allies such as Dr. Ashish Jha, then dean of the Brown University School of Public Health and now Biden’s COVID-19 Response Coordinator, said he was “deeply worried” about the speed of vaccine development. Dr. Ezekiel Emanuel, a noted bioethicist, former Obama advisor, and then advisor to the Biden campaign, organized a letter, with multiple signatories, urging Pfizer to defer seeking vaccine authorization until “at least late November.”
A September 10, 2020 editorial in the Journal of the American Medical Association fueled doubts by claiming that “some” unnamed and uncited persons were concerned that political appointees would, “insist on an EUA for a vaccine over the recommendation of FDA career scientists.” It claimed that Dr. Hahn, had “indicated that the FDA is willing to use an Emergency Use Authorization (EUA) for vaccines before phase 3 trials are complete.”
Yet the editorial cited an August 7 JAMA article authored by FDA officials including Drs Hahn and Marks — “Unwavering Regulatory Safeguards for COVID-19 Vaccines” — in which they committed to only issuing an EUA once a phase 3 trial or interim analysis of such a trial that met pre-specified success and safety criteria was complete. In addition, the editorial writers surely knew that any authorization would only occur following a public discussion at the FDA’s Vaccines and Related Biological Products Advisory Committee.
Mainstream media “fact checkers” amplified public doubts. The Washington Post, for example, stated that Trump was “misrepresenting how fast a vaccine will be available.” NBC news asserted vaccines by year end would be a “miracle.”
The House report has the story backwards. Trump administration officials urged speed in vaccine development to save lives, not for political gain. President Trump would have, no doubt, been thrilled to have an announcement of effectiveness or vaccine authorization prior to the election — what politician in his position would not have?
But there is no evidence that he unduly pressured the FDA or undermined its scientific processes. Nor is there evidence that he forced Pfizer to publicly predict when it would have effectiveness data and be able to apply for authorization.
It was pressure from candidates Biden and Harris and their allies that forced the FDA to revise its guidelines and delay vaccine authorization. That same pressure likely influenced a Pfizer decision to alter its research protocol on when to first assess vaccine efficacy that changed their announcement of vaccine efficacy from pre- to post-election.
Moreover, contrary to the report’s implication that there was a tremendous delay between the submission of the proposed revised guidelines to the White House and their public release, the total process took only two weeks. And while the report claims the FDA had to defy the administration to release the new guidelines, Hahn’s testimony was that the White House approved the guidelines, unchanged, before they were released on October 6.
If the American people want to know who injected politics into science, delaying vaccines and causing thousands of unnecessary deaths, they need look no further than the current White House and its media and academic enablers.
Joel Zinberg, MD, is a senior fellow at the Competitive Enterprise Institute and director of public health and wellness at the Paragon Health Institute.
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