Akero NASH Drug Reduced Liver Fat to Normal Levels, Reversed Fibrosis: Study

 Akero Therapeutics, Inc. (Nasdaq: AKRO), a cardio-metabolic biotechnology company developing transformational treatments for non-alcoholic steatohepatitis (NASH), today announced that full results of the main portion of its Phase 2a BALANCED trial in biopsy-confirmed NASH patients with F1-F3 fibrosis have been published in Nature Medicine.

The manuscript, available at this link, provides a comprehensive analysis showing that pre-cirrhotic NASH patients treated for 16 weeks with Akero’s investigational drug, efruxifermin (EFX), an FGF21 analog, achieved substantial reductions in liver fat, associated with decreases in markers of liver injury and inflammation, and reversal of fibrosis after only 16 weeks treatment. Numerous endpoints are reported for the first time in Nature Medicine.

“This disclosure of EFX data in Nature Medicine marks the first published clinical evidence of fibrosis regression with an FGF21 analog and what we believe are the largest reductions in liver fat publicly reported to date across all NASH investigational drug classes,” said Kitty Yale, chief development officer of Akero. “We’re pleased to contribute to the field of NASH clinical research with publication of these data. We extend gratitude to the trial participants who made this study possible.”

NASH is a serious, potentially life-threatening condition that is a leading cause of liver failure and liver transplantation globally. An estimated 17.3 million Americans had NASH in 2016, a number that is expected to increase to 27.0 million by 2030. There are currently no approved therapies for NASH. Weight loss of 10 percent or more has been shown to reverse NASH by restoring normal levels of liver fat and reducing insulin resistance. Unfortunately, achieving this degree of weight loss through lifestyle change is very challenging.

https://finance.yahoo.com/news/study-published-nature-medicine-shows-151000885.html

Moderna's first seasonal flu vaccine slides into clinic as pharma giants crowd into mRNA

 Now that mRNA technology has the FDA’s backing, Moderna has moved on to its next act, a vaccine to improve upon the annual flu shot, as plenty of Big Pharma giants breathe down the biotech's neck.

The Cambridge, Massachusetts-based company, made famous by the success of its COVID-19 vaccine, has dosed the first patient in a phase 1/2 clinical trial for a new seasonal influenza vaccine.

Moderna is developing mRNA-1010 to protect against common flu strains as recommended by the World Health Organization. The company is hoping to improve on traditional flu shots which are typically about 40% to 60% effective. Most of these shots are developed using eggs, which Moderna said can cause unintended changes to the vaccine virus. The strains to be used in the vaccines are also decided six to nine months ahead of time, meaning a lot of guesswork as to which strain might be dominant during flu season.

The clinical trial for mRNA-1010 will ultimately enroll 180 healthy adults to test the vaccine’s safety, how patients react and how well it works.

Moderna enters the clinic surrounded by giants on all sides—from Sanofi to Pfizer to GlaxoSmithKline—who believe with the success of the COVID-19 vaccines, that mRNA is a new frontier for vaccine development.

Working with Translate Bio, Sanofi claimed to have commenced the first human trial of a seasonal mRNA flu vaccine candidate in June, beating Moderna and other rivals to the clinic.

The technology works by teaching a patient’s cells to make a protein that can trigger an immune response in the body and spur the creation of antibodies and therefore protection against a virus. While the authorization of the COVID-19 vaccines marked the first time mRNA had been cleared by regulators, the technology has been studied for decades.

Moderna has used mRNA vaccines in trials before, though aimed at specific flu strains: Back in 2019, it dropped early data from several phase 1 tests showing its mRNA vaccines against H10N8 and H7N9 influenza viruses "were well-tolerated and elicited robust immune responses."

This latest attempt is aiming wider using a seasonal approach that targets multiple strains, including influenza A H1N1, H3N2 and influenza B Yamagata and Victoria.

Pfizer, which developed an mRNA COVID-19 vaccine that beat Moderna to the U.S. market last year, sees mRNA becoming a large part of the pharmaceutical giant’s future. The company thinks the 95% efficacy seen with the COVID-19 vaccine could translate into a major improvement for the yearly flu shot.

Sanofi last month announced plans to throw $476 million a year to a dedicated vaccines mRNA Center of Excellence in an effort to become a leader in developing mRNA vaccines against a wide range of infectious diseases.

And then there’s GSK, which is working with CureVac on five clinical-phase mRNA-based vaccines through a $294 million deal.

In addition to the flu, Moderna is developing vaccines for HIV, respiratory syncytial virus and others.

The biotech is also looking at combining some vaccines into one single shot. Other companies have beaten them to the punch there, too, such as Novavax, which is already testing a COVID-flu vaccine in animals.

“Respiratory combination vaccines are an important pillar of our overall mRNA vaccine strategy,” said Moderna CEO Stéphane Bancel in a statement. “Our vision is to develop an mRNA combination vaccine so that people can get one shot each fall for high efficacy protection against the most problematic respiratory viruses.”

https://www.fiercebiotech.com/biotech/moderna-s-first-flu-vaccine-candidate-slides-into-clinic-as-pharma-giants-crowd-into-mrna

Cel-Sci CEO tries to spin cancer trial failure into a win

 Cel-Sci CEO Geert Kersten begged investors in 2018 to hold on until phase 3 data could prove the struggling biotech’s cancer drug worked. Fast forward to 2021: The results are in, and they are unlikely to inspire the rally needed to save the company.

The biotech's stock price plummeted 45%, losing more than $11 per share and dropping to $13.69 after the news was issued June 28. The tumble has continued, with the stock sitting at about $8.38 apiece Wednesday.

Kersten has turned to his keyboard once again in an effort to spin the results for Multikine into a win.

“Some false assertions and misrepresentations have been made and published by parties who either did not understand the protocol and statistical analysis or had ulterior motives pertaining to our stock price,” Kersten wrote in a letter to stockholders published Wednesday.

Here’s what the results said: Multikine failed to improve overall survival when added to standard of care treatment in the overall population tested in the phase 3 head and neck cancer study. Cel-Sci wanted to see at least a 10-percentage point improvement on this metric when Multikine was added to standard of care, comprising surgery, radiotherapy and chemotherapy. This was the main goal of the trial, meaning the test was unsuccessful.

But Cel-Sci plans to file the drug for FDA approval anyway, focusing on a narrow subset of patients who did not receive the chemotherapy part of their treatment. The study showed a 14-percentage point improvement in overall survival in this group.

This is where Kersten believes the “confusion” arises from. By confusion, he means an investor revolt that has turned into at least one class action lawsuit from shareholders alleging the company’s officers and/or directors engaged in securities fraud or unlawful business practices.

According to Kersten, the data spurred accusations that the company had engaged in “data mining” and “p-value hacking.” Cel-Sci was accused of sitting on the data for a year before landing on the subgroup analysis as a way to move the therapy forward anyway. Questions arose as to whether Cel-Sci could even use the subgroup data for a filing because they were not prespecified in the study’s initial endpoints.

Kersten cited an unnamed statistician to support his case that no mining or hacking had occurred. He claimed the subgroup analysis was prespecified, meaning the company can use these data to file for FDA approval. He also said the p-value data were “in fact very strong.”

The p-value measures the probability that the effect observed in the trial is a result of the experimental treatment and not merely chance. The lower the number, the better it is for the study. Cel-Sci reported that the overall survival results for Multikine plus standard of care without chemotherapy showed a p-value of 0.0236.

Kersten complained that short sellers had targeted the company before the results were issued and therefore had an interest in seeing the shares plummet.

“But now, the data clearly shows that Multikine extends life in 40% of newly diagnosed advanced primary head and neck cancer patients,” Kersten wrote. He said that if Multikine is cleared by the FDA, tens of thousands of patients with head and neck cancer may live longer. “What kind of person continues to sell short and attack a company that can make this kind of difference in the lives of cancer patients?”

Back in 2018, Kersten’s letter pointed to this data release as a “key inflection point” that could right the ship after several rocky years. He promised the biotech had a "promising future" ahead. 

In reality, Cel-Sci had just made a pitch to the New York Stock Exchange to try to hang on to its listing, stockholders had an equity deficit and the company reported net losses on the five prior fiscal years. The company was also emerging victorious from a lawsuit with a contract research organization that was involved in a phase 3 study for head and neck cancer that ran from 2011 to 2013. The legal action had shaken the confidence of investment funds and analysts, but Kersten said at the time that the win should put the hesitation to bed.

 

Despite all of those events, Kersten believed the company was way undervalued at the time.

In a December 2020 (PDF) 10-K filing, Cel-Sci calculated its net losses at $384 million since inception, with $30.2 million clocked for fiscal year 2020. The company has not commercialized any products and receives revenue only through the sale of securities. This is expected to continue "for the foreseeable future."

"Multikine is the only product candidate in late-stage clinical development, and Cel-Sci’s business currently depends heavily on its successful development, regulatory approval and commercialization," the filing stated.

The FDA has not cleared a new drug for this type of advanced head and neck cancer in decades. Cel-Sci will now take the data to the FDA for a meeting ahead of a regulatory filing for patients to receive Multikine followed by surgery and radiation—but not chemotherapy.

Cel-Sci clearly hopes the subgroup will push Multikine—and the company—to a new inflection point.

https://www.fiercebiotech.com/biotech/data-mining-and-p-value-hacking-cel-sci-ceo-tries-to-spin-cancer-trial-failure-into-a-win

AstraZeneca-Amgen drug gets FDA's speedy review for asthma

 Drugmaker AstraZeneca AZN.L said on Thursday its experimental drug tezepelumab was granted a speedy review by the U.S. Food and Drug Administration for potential approval as a treatment for asthma, with action expected in the first quarter next year.

The medicine, developed along with U.S-based Amgen AMGN.O, showed in trials it can reduce asthma attacks in patients with severe and uncontrolled forms of the respiratory condition, with promise for wider use against different triggers.

https://www.nasdaq.com/articles/astrazeneca-amgen-drug-gets-fdas-speedy-review-for-asthma-2021-07-08

Biogen, FDA walk back controversial Aduhelm label after weeks of fierce criticism

 Following weeks of fiery criticism for its wide-labeled approval for Biogen’s Aduhelm for anyone with Alzheimer’s disease, the FDA is now narrowing the recommended window of patients to only those with milder forms of the memory-robbing disease. 

Biogen on Thursday said the FDA approved an updated label for Aduhelm, also known as aducanumab, that recommends the amyloid-beta targeting antibody for people with mild cognitive impairment or mild dementia, aligned with those included in Biogen’s late-stage trials. 

The FDA warns that there is “no safety or effectiveness data on initiating treatment at earlier or later stages of the disease than were studied.” 

Biogen requested the update based on “ongoing conversations with prescribing physicians, FDA and patient advocates,” research head Alfred Sandrock, Jr., M.D., Ph.D., said in a statement. The goal is to “further clarify the patient population that was studied across the three Aduhelm clinical trials that supported approval,” Sandrock added.

The slimmed approval follows the FDA’s decision to award Aduhelm an “almost shockingly broad” label, as some analysts put it, in early June, essentially giving Biogen free reign to the estimated 6 million Alzheimer’s patients living in the U.S. 

Intense pushback followed as market watchers pointed out that the drug could overwhelm payer budgets, particularly Medicare, which covers most Alzheimer's patients in the U.S.

Although Biogen’s label update comes just over a month since Aduhelm’s initial approval, it follows a string of stinging rebukes, including from high-ranking lawmakers, against the Cambridge-based drugmaker. 

On Capitol Hill, Biogen has faced criticism over its $56,000 per year list price for Aduhelm, the only approved drug intended to slow the progression of the disease. In some estimations, given the FDA’s expansive go-ahead, Aduhelm could eventually balloon Medicare’s spending above the cost of all current Part B drugs. 

That’s all for a drug that has shown murky clinical benefits, at best, critics argue. Both Biogen and the FDA are now the subjects of a Congressional probe, spearheaded by the House Committee on Oversight and Reform, over the company’s pricing tactics, as well as the FDA’s approval process. 

As more details surrounding Aduhelm’s approval come to light, prominent Democratic lawmakers have targeted the FDA’s dealings with the drugmaker initiated well before the treatment was cleared in June. In a letter to the HHS on Tuesday, Rep. Katie Porter, D-California, charged Biogen with “undue influence” over the FDA’s review process.

https://www.fiercepharma.com/pharma/facing-pushback-biogen-and-fda-agree-to-narrow-aduhelm-s-broad-label

Vor Biopharma to Collaborate with Janssen onc Stem Cell Transplant- Antibody Combo for Acute Myeloid Leukemia

 Vor Biopharma (Nasdaq: VOR or the Company), a cell therapy company pioneering engineered hematopoietic stem cell (eHSC) therapies combined with targeted therapies for the treatment of cancer, today announced the formation of a collaboration with Janssen Biotech, Inc. (“Janssen”), one of the Janssen Pharmaceutical Companies of Johnson & Johnson. The agreement was facilitated by Johnson & Johnson Innovation.

Under the terms of the collaboration, Vor Biopharma will investigate the combination of these two technologies into a treatment solution, pairing Vor’s “invisible” eHSC transplant platform with one of Janssen’s bi-specific antibodies in development for acute myeloid leukemia (AML).

“We are thrilled to enter into this collaboration with Janssen as we continue to explore our platform’s potential to pair with a broad spectrum of targeted therapy modalities for the treatment of patients with blood cancer,” said Tirtha Chakraborty, PhD, Vor’s Chief Scientific Officer. “We believe this unique combination will leverage each technology’s strengths, while protecting patients against off-target effects of these powerful immunotherapies.”

The collaboration agreement provides that each company retains all rights and ownership to their respective programs and platforms.

https://finance.yahoo.com/news/vor-biopharma-announces-collaboration-janssen-120000238.html

Can-Fite to Initiate Pivotal Phase III Liver Cancer Study

 Can-Fite BioPharma Ltd. (NYSE American: CANF) (TASE: CFBI), a biotechnology company advancing a pipeline of proprietary small molecule drugs that address inflammatory, cancer and liver diseases, today announced it has completed preparatory work ahead of the anticipated initiation of patient enrollment for its pivotal Phase III registration trial of Namodenoson in the treatment of hepatocellular carcinoma (HCC), the most common form of liver cancer.

Can-Fite has received agreement from both the U.S. Food and Drug Administration (FDA) and European Medicines Agency (EMA) on the protocol and plans to submit it for Institutional Review Board (IRB) approvals in the coming weeks. Namodenoson has Orphan Drug status with both the FDA and EMA, as well as Fast Track Status with the FDA for the treatment of HCC. A compassionate use program has been ongoing in Israel.

The double blind, placebo-controlled trial will enroll 450 patients diagnosed with HCC and underlying Child Pugh B7 (CPB7) through clinical sites worldwide. Patients will be randomized to oral treatment with either 25 mg Namodenoson or matching placebo given twice daily. The primary efficacy endpoint of the trial is overall survival. Other oncology trial efficacy outcomes such as tumor radiographic response rates and median progression-free survival, as well as standard safety parameters, will be assessed.

The Company plans to conduct an interim analysis by an Independent Data Monitoring Committee (IDMC) after 50% of enrolled patients are treated. Namodenoson will be evaluated as a 2nd or 3rd line treatment for CPB7 patients in whom other approved therapies have not been or are no longer effective.

https://www.businesswire.com/news/home/20210708005319/en/Can-Fite-Gears-Up-to-Initiate-Pivotal-Phase-III-Liver-Cancer-Study