uniQure's hemophilia B gene therapy candidates show long-term benefit

 

• uniQure (NASDAQ:QURE) announces updated clinical data on the three patients treated in its ongoing Phase 2b study evaluating its gene therapy candidate etranacogene dezaparvovec, for the treatment of hemophilia B. Data were presented at the American Society of Hematology.
• Two-year follow-up data show that all three patients have sustained FIX activity (a protein that helps blood form clots to stop bleeding) after the one-time administration of etranacogene dezaparvovec. Mean FIX activity was 44.2% of normal (compared to 41% of normal at 52 weeks).
• At two years after dosing, two of the three participants remain free from bleeds and use of FIX replacement therapy. A single bleed has been reported in one participant, who has used a total of two FIX infusions (excluding surgery). All patients have remained free of prophylaxis in the two years since receiving etranacogene dezaparvovec.
• Additionally, the company announced presentation of up to 5 years of follow-up data on the 10 patients in the Phase 1/2 trial of AMT-060, its gene therapy for the treatment of hemophilia B. All 10 patients continue to show long-term clinical benefit, including sustained increases in FIX activity, reduced usage of FIX replacement therapy, and decreased bleeding frequency. At up to 5 years of follow-up, AMT-060 continues to be well-tolerated, with no new treatment-related adverse events.
• https://seekingalpha.com/news/3642295-uniqures-hemophilia-b-gene-therapy-candidates-show-long-term-benefit

Editas up after unveiling novel gene editing to treat hemoglobinopathies

 

• Editas Medicine (NASDAQ:EDIT) joins the gene-editing bandwagon as the company showcases promising pre-clinical data and successful development of a large-scale manufacturing process for EDIT-301, the company’s gene-editing treatment for sickle cell disease and beta-thalassemia.
• The data announced over the weekend at the 62nd Annual Meeting and Exposition of the American Society of Hematology demonstrate high levels of editing in CD34+ cells from normal donors and sickle cell patients, leading to robust fetal hemoglobin induction. The company expects an IND filing for the treatment by the end of 2020, and shares surged +13.2%.
• Sickle cell disease, an inherited blood disorder impacting an estimated 100,000 people in the United States, leads to polymerization of the sickle hemoglobin protein, which is inhibited by fetal hemoglobin.
• "These findings are very encouraging and further support our novel approach to developing and manufacturing EDIT-301 as a best-in-class and durable medicine for the potential treatment of sickle cell disease and beta-thalassemia,” said Charles Albright, Ph.D., Executive Vice President, and Chief Scientific Officer, Editas Medicine.
• Additionally, the company announced that its large-scale manufacturing process for edited CD34+ cells from normal donors was consistent and robust.
• During the ASH meeting, CRISPR Therapeutics (NASDAQ:CRSP) and Vertex Pharmaceuticals (NASDAQ:VRTX) also demonstrated promising data from Phase 1/2 clinical studies for CTX001, an investigational therapy for patients suffering from TDT (transfusion-dependent beta-thalassemia) and severe SCD (sickle cell disease)currently undergoing Phase 1/2 clinical trials.
• https://seekingalpha.com/news/3642287-editas-medicine-surges-13-after-unveiling-novel-approach-to-gene-editing-therapies-to-treat

ASH: Regeneron bispecific banishes lymphoma—even in patients failed by CAR-T

 CAR-T therapies have been a game changer in certain blood cancers, but they aren't a complete solution. For starters, not all patients can get CAR-T treatment, while others see their cancer worsen despite receiving it.

But Regeneron’s bispecific antibody could be a new option for those patients. The drug beat cancer back in two kinds of lymphoma in a phase 1 study, eliminating tumors in 70% of patients with follicular lymphoma (FL) and in 21% of patients with diffuse large B-cell lymphoma (DLBCL) who had not tried a CAR-T therapy.

The study, presented virtually Sunday at the annual meeting of the American Society of Hematology, found the treatment, odronextamab, did even better in DLBCL patients who had never received CAR-T treatment, banishing tumors in 55% of those patients.

The study tested various dose levels of odronextamab, a bispecific antibody targeting CD3 and CD20, in 127 patients with various non-Hodgkin lymphomas. That included 71 patients with DLBCL and 37 patients with FL. The patients had tried a median of three other treatments, with some receiving as many as 11 prior treatments. Of the 71 patients with DLBCL, just over one-third had tried a CAR-T therapy, namely Novartis’ Kymriah or Gilead’s Yescarta. In addition to being approved for the treatment of DLBCL, Kymria and Yescarta are also in the hunt for nods in FL.

Odronextamab’s effects were long-lasting, too. Of the 70% of FL patients whose tumors were cleared, 81% were still responding to treatment up to 41 months later. The numbers were similar in the DLBCL patients who hadn’t tried CAR-T therapy—of the 55% of patients who saw their tumors banished, 83% were still responding up to 21 months later.

The most common side effects were fever, affecting about three-quarters of the patients, and cytokine release syndrome (CRS), affecting 62% of patients. CRS is an inflammatory response that can happen after treatment with certain types of immunotherapies and is a common side effect of CAR-T therapies. Most of the cases of CRS seen in the study were mild or moderate, though, and no patients quit the study because of CRS.

“It is important to note that CRS occurs almost universally in the first one to two weeks,” said Andres Sirulnik, M.D., Ph.D., senior vice president of translational and clinical sciences, hematology at Regeneron. The company thinks its approach of stepping up patients’ doses in the first two weeks before hitting the target dose in Week 3 has helped it reduce the risk of severe CRS, he added.

Although CAR-T therapies have transformed the treatment of patients with DLBCL and other blood cancers, there remains room for improvement. The available CAR-T therapies are made from a patient’s own cells in a process that can be complicated and time-consuming.

“CAR-Ts are excellent tools to combat this disease, but on the other hand, they’re not available to everybody and we even have patients now that are starting to show progression in spite of CAR-T therapies,” Sirulnik said. The need for new last-line treatments for these kinds of blood cancer remains, he added.

“The CAR-T therapies available to a subset of patients have already shown themselves to be long-lasting therapies,” Sirulnik said. With odronextamab, Regeneron hopes to deliver similarly long-lived responses that are easier to administer to patients and be available to more people.

One other advantage of an antibody over CAR-T is the ability to adjust treatment after it’s started. Doctors may tweak the dose of odronextamab, or stop giving the drug entirely, if the patient is suffering side effects—something that can’t be done with CAR-Ts.

Regeneron has already started a phase 2 study of odronextamab that it hopes to finish enrolling in the first half of 2021, Sirulnik said. If all goes well, the company plans to conduct phase 3 confirmatory studies in FL and DLBCL in earlier lines of treatment, including second-line DLBCL and first-line FL. Further down the line, Regeneron hopes to combine odronextamab with the next generation of bispecifics in its pipeline to see whether they can deliver better results together.

https://www.fiercebiotech.com/biotech/ash-regeneron-s-bispecific-banishes-lymphoma-even-patients-failed-by-car-t

AbCellera, tapped by Lilly for COVID-19 antibody therapy, sets IPO terms with $5B valuation

 Canada’s speedy R&D engine AbCellera, now world-renowned for its tech producing the Eli Lilly COVID-19 drug authorized by the FDA, has set terms for a monster IPO.

The Vancouver-based company, which is not a biotech but uses artificial intelligence to speed up drug research, plans to raise a massive $357 million on the Nasdaq by offering 23 million shares at a price range of $14 to $17, with the company valued at the midpoint range at around $5 billion. Its ticker will be "ABCL."

The 2020 Fierce 15 winner was tapped by Lilly to find the human anitbody bamlanivimab (LY-CoV555) earlier this year. The Big Pharma swiftly developed the drug and last month got off an emergency use agreement with the FDA to treat certain COVID-19 patients, putting AbCellera on the map.

In March, AbCellera got off a $105 million series B from the likes of Peter Thiel, PayPal founder and tech/occasional life science investor, and Eli Lilly. In May, Canada's government also gave it a financial boost, pledging up to $175.6 million in support under the Innovation, Science and Economic Development Canada's Strategic Innovation Fund.

Now, it’s going public in the hope of getting more of its antibody work, which includes areas outside of COVID-19, out to partners.

https://www.fiercebiotech.com/biotech/abcellera-tapped-by-lilly-for-its-covid-antibody-therapy-sets-ipo-terms-5b-valuation

ASH: AstraZeneca's Calquence, BeiGene's Brukinsa turn heads with new data

 Johnson & Johnson and AbbVie’s Imbruvica currently reigns supreme in the previously untreated chronic lymphocytic leukemia (CLL) market. But newer members of its class are threatening, and both put up data over the weekend in other cancer types that might catch the attention of CLL prescribers down the line.

Sunday at the American Society of Hematology virtual annual meeting, AstraZeneca touted long-term phase 2 Calquence results showing previously treated mantle cell lymphoma (MCL) went a median 22 months without seeing their cancer worsen. And at three years of follow-up, more than half of patients taking Calquence were still alive.

The way AZ sees it, “the fact that we’re seeing a number of patients with deep, durable responses over time is helpful for reinforcing the efficacy of the medicine”­—even outside of MCL, Dave Fredrickson, EVP and global head of AstraZeneca’s oncology business unit.

And the numbers are particularly noteworthy considering that MCL “is an aggressive and difficult-to-treat blood cancer. It’s diagnosed at an advanced stage, and patients become resistant to treatment,” he added.

Specifically, AstraZeneca is hoping the data reinforce the case for Calquence in CLL—a much larger market. The BTK inhibitor won a first-line nod in the disease last November, setting up an in-class showdown with Imbruvica.

Since then, AZ’s drug has gone on to capture 35% of new CLL patients, and Fredrickson predicts that number could rise to 50% by the launch’s 18-month mark. One reason? Calquence’s safety and tolerability profile. “The medicine itself is resulting in really good experiences for physicians and their patients,” he said.

But Calquence isn’t the only BTK inhibitor looking to give Imbruvica a run for its money in CLL. BeiGene’s Brukinsa, which scored its first FDA go-ahead last year with a green light in MCL, is on a collision course with both Imbruvica and Calquence in that arena.

Sunday at ASH, industry watchers got a look at the drug in marginal zone lymphoma (MZL), another B-cell malignancy, where Brukinsa showed it could provoke a response in 74% of patients and obliterate cancer completely in 24% of them after just 10.7 months of follow-up.

Imbruvica, in its own phase 2 MZL trial, spurred a benefit in 48% of patients and eliminated cancer in 5% of them after one year of follow-up.

“What it tells me really is that consistently, across every tumor type, we are seeing numerically better overall response rates, as well as higher complete response rates, than may have been historically seen with other BTK inhibitors,” said Jane Huang, M.D., BeiGene’s chief medical officer in hematology.

While “it can be challenging” to compare numbers across trials, in part because of differences in patient populations, “I think you can look at general trends,” she added.

BeiGene is also looking to Brukinsa’s safety profile for an advantage over its older rival—and in that department, it has head-to-head data it can point to.

Last December, the company trumpeted phase 3 results in Waldenstrom macroglobulinemia showing that just 2% of patients experienced atrial fibrillation, compared with 15% of those taking Imbruvica.

“In general, investigators feel that for the most part safety is extrapolatable to other diseases,” Huang noted.

BeiGene will no doubt be referencing that head-to-head safety win as it moves into first-line CLL, where it could have phase 3 data as soon as next year, Huang said.

https://www.fiercepharma.com/pharma/ash-astrazeneca-s-calquence-beigene-s-brukinsa-turn-heads-new-data-putting-imbruvica-notice

Trump to sign order giving priority access for COVID vaccines to Americans

President Donald Trump will sign an executive order on Tuesday to ensure that priority access for COVID-19 vaccines procured by the U.S. government is given to Americans, a senior administration official said on Monday.

https://www.marketscreener.com/quote/stock/MODERNA-INC-47437573/news/Trump-to-sign-order-giving-priority-access-for-COVID-vaccines-to-Americans-31956904/

For Airlines, Dry Ice in Vaccine Transport Demands Special Attention

 The large amounts of dry ice needed to speed Covid-19 vaccine candidates to pandemic-weary populations will call for special attention from airlines and safety regulators.

Dry ice, the solid form of carbon dioxide, is a critical part of plans to transport the vaccine developed by Pfizer Inc. and BioNTech SE, which must be kept at ultracold temperatures. Pfizer expects to ship 50 million doses world-wide by the end of the year. The vaccine was the first to be approved in the West, receiving clearance for emergency use in the U.K. last week. It is under review by the Food and Drug Administration in the U.S.

Widely used as a refrigerant, dry ice is classified as a dangerous good by the International Civil Aviation Organization and the U.S. Department of Transportation because it changes to gas form as it breaks down, a process called sublimation. Shippers must use ventilated containers that allow the gas to release, to prevent pressure from building up and rupturing the packaging.

The gas can also displace oxygen in confined spaces with poor ventilation, creating a suffocation hazard, though the risk is minimal under normal cabin ventilation, according to the Federal Aviation Administration.

"If oxygen levels get down below 19%, that could cause a hazard to people and animals," said Delmer Billings, technical director for the Dangerous Goods Advisory Council, a nonprofit trade group that promotes safe transportation of hazardous materials. "If you deplete oxygen sufficiently, it could cause unconsciousness, even death," he added.

Air carriers involved in vaccine transport efforts are asking aviation regulators to increase the amount of dry ice they are allowed to carry on flights hauling vaccines as they work with drugmakers and governments to set up distribution channels. Restrictions on the amount of the material on planes are typically based on aircraft ventilation rates and factors such as the size of the plane and whether it is used for passenger or cargo flights, said Robert Coyle, senior vice president of pharma and healthcare strategy at freight forwarder Kuehne + Nagel International AG.

On Thursday, Delta Air Lines Inc. said it had received FAA approval to double the allowed load of dry ice on its Airbus A330 and A350 wide-body jets, and six times the prior allowed load for shipments using a special suitcase-sized storage container that Pfizer designed.

Delta has done trial runs with vaccine cargoes from Europe and to Latin America, and within the U.S., all on cargo-only flights.

United Airlines Holdings Inc. secured FAA approval last month to boost its dry-ice allowance to 15,000 pounds from 3,000 pounds, for chartered cargo flights between Brussels International Airport and Chicago O'Hare International Airport to support distribution of the Pfizer and BioNTech vaccine. A United spokeswoman said the airline "has effective procedures in place to ensure we safely handle all the hazardous materials we are permitted to carry on board our aircraft."

Extremely cold with a surface temperature of about minus-78 degrees Celsius, dry ice has long been used to ship medicine, pharmaceutical products and perishable food such as meat or ice cream.

"When packaged and stored properly, it poses no risk," said Rafael Teixeira, president of World Courier and ICS, a specialty logistics provider owned by drug distributor AmerisourceBergen Corp.

The scale of the Covid-19 vaccine distribution effort is unprecedented, involving billions of doses with strict temperature-control requirements that are expected to strain cold-chain shipping networks.

The Pfizer and BioNTech shots must be kept at minus-70 degrees Celsius -- colder than the average annual temperature at the South Pole and lower than some other vaccine candidates require. Moderna Inc.'s shot, the other leading front-runner, must be shipped and stored at a below-freezing temperature that most home or medical freezers can accommodate.

Makers of dry ice are bracing for an expected demand surge. Logistics providers have been building "freezer farms" with hundreds of portable units that store pharmaceuticals at ultralow temperatures.

Plymouth, Minn.-based Pelican BioThermal LLC, which makes packaging that typically uses engineered materials to maintain temperatures, has tested and approved the use of dry ice in its systems to provide the sub-frozen temperatures needed to maintain the efficacy of Covid-19 vaccines. The company is also ramping up global production of its large shipping containers that can hold full pallets of goods on rising demand from pharmaceutical companies looking to ship vaccines.

"There are a lot of investments being made right now to get this done," said Ira Smith, director of Pelican's rental program in the Americas.

https://www.marketscreener.com/quote/stock/PFIZER-INC-23365019/news/For-Airlines-Dry-Ice-in-Vaccine-Transport-Demands-Special-Attention-31957019/