Japan COVID Cases Hit 1 Million as Infections Spread

 Japan reached the milestone of one million coronavirus cases on Friday, domestic media reported, as infections surged in Olympic host Tokyo to other urban areas and the country grapples with an unprecedented speed of spread of the Delta variant.

With a record 15,645 new cases reported on Friday, the total since the pandemic began last year is now above one million, tarnishing Japan's early success in containing the disease.

It still has the lowest cumulative cases per population among the Group of Seven most industrialised countries, less than a tenth of U.S. and one-fifth of German cases.

The number increased by 144,000 since the Tokyo Olympics began on July 23. Prime Minister Yoshihide Suga reiterated that he did not think holding the Games contributed to rising infections.

New cases in Tokyo hit 4,515, the second highest after Thursday's record 5,042, while the neighbouring, populous prefecture of Kanagawa saw its cases soaring to 2,082, quadrupling in less than two weeks.

Infections in Osaka, the biggest city in the country's west, also rose to a record-breaking 1,310, in a sign the virus is quickly spreading outside Tokyo.

While infections appear to quickly spread from the capital to other regions, Suga struck a cautious tone on expanding a state of emergency to the entire country.

"We need to take into account local conditions. Each region can take their own step," Suga told reporters in Hiroshima, where he attended a ceremony to commemorate the 76th anniversary of the atomic bombing.

Still, the worsening health crisis - which led the government to tighten its guidelines on hospitalisations - is likely to put pressure on Suga ahead of an election that must be held by October.

Suga also said any decision on whether to allow spectators in the Paralympics, scheduled on Aug. 24-Sept. 5, will be made after the end of the Olympics on Aug. 8.

https://www.usnews.com/news/world/articles/2021-08-06/japan-covid-cases-hit-1-million-as-infections-spread-beyond-tokyo

Dicerna’s stock sinks as Alnylam rival shows mixed data, stymieing approval filing

 After finding success with one RNAi candidate for a rare metabolic disorder that impacts the kidneys called primary hyperoxaluria 1, Dicerna Pharmaceuticals was hopeful that a second RNAi candidate would be able to tackle other types of PH. However, the company released mixed results from what was meant to be a pivotal study for nedosiran, sending its shares down some 13% when the markets opened today.

The phase 2 trial showed efficacy in one PH type but not another, meaning Dicerna will not be able to seek approval in PH2 for now. There are three forms of the disease, all of which are closely related and characterized by high urinary oxalate levels that cause frequent kidney stones and progression to end-stage renal disease. Dicerna designed nedosiran to silence a gene involved in what it believes to be the ultimate step in the oxalate production pathway, thereby enabling it to treat PH1, PH2 and PH3 with the drug.

The pivotal data raise significant doubts about the use of nedosiran in PH2. Across the mix of 34 PH1 and PH2 patients with at least one efficacy assessment, nedosiran drove a statistically significant drop in urinary oxalate. However, the overall result masks variation between PH1 and PH2 patients. 

Urinary oxalate levels fell sharply in the cohort of 17 PH1 patients who received nedosiran, while the average rose in the 11 subjects on placebo. In the PH2 group, urinary oxalate levels rose slightly in the five patients who received nedosiran and fell in the one subject on placebo. Having seen strong effects in a PH2 mouse model, Dicerna was taken back by the results.  

“This was a surprise, and at this point we do not have a hypothesis that's not in the realm of rank speculation for what happened,” Dicerna CEO Douglas Fambrough, Ph.D., told investors on a conference call to go over the results. 

Dicerna has gone back and looked at data from another study, and “it does appear that those three patients are deriving benefit as shown by reductions in urinary oxalate levels sustained over time,” Fambrough said. Work is underway to assess whether something happening outside the liver is affecting the PH2 patients, but, for now, Dicerna is in the dark.

The impact on Dicerna’s go-to-market plans is clearer. Fambrough said the results don’t support including the PH2 indication in the NDA Dicerna plans to submit to the FDA in the fourth quarter. As it stands, Dicerna plans to focus on PH1 in the submission, although it may adjust its strategy based on the results of a PH3 trial that is due to read out early in the fourth quarter.

Alnylam won FDA approval for Oxlumo in PH1 late last year, but that RNAi drug has a mechanism of action that isn't expected to work in PH2 or PH3. Dicerna, by targeting a later step common to all PH types, sought to secure a broader label. The failure to generate the data to support such broad use leaves Dicerna facing the prospect of going head-to-head with Alnylam for PH1 patients. 

https://www.fiercebiotech.com/biotech/mixed-pivotal-data-dicerna-rival-to-alnylam-drug-sinks-stock

Moderna is ready to spend billions in COVID-19 cash on gene editing

 Moderna has found a direction to volley their mountain of COVID-19 vaccine cash: gene editing.

Executives revealed during a second-quarter earnings call Thursday that Moderna is ready to “expand our horizons” with external technologies or products. Read: They’re ready to start buying.

Plenty of speculation has built up around Moderna’s dealmaking strategy as the biotech pulled in billions with its COVID-19 vaccine. The shot, which the company now aims to market as Spikevax, is expected to bring in about $20 billion this year based on existing orders.

Moderna is interested in new opportunities in nucleic acid technologies, gene therapy, gene editing and mRNA, CEO Stéphane Bancel said during the conference call. The company—which literally trades under the symbol MRNA—is also interested in new delivery technologies that could expand its existing mRNA work.

“We would be interested in technology licenses and/or in development candidate licenses and/or, if it makes sense, M&A,” Bancel said. “You can count on us to be disciplined.”

One thing Moderna is not interested in is small or large molecule candidates, “even if they could complement our commercial portfolio,” the chief executive said, because “we love information molecules too much.”

Unsurprisingly, analysts wanted more on the gene editing news, although executives largely faced questions about COVID-19 vaccine boosters during the Q&A. Moderna President Stephen Hoge piped up to say the company has been watching the gene editing field closely and considering where its mRNA technology could help with “delivering gene-editing cargoes” to different tissues.

“We think it's the right time for us to start to expand in that direction,” Hoge said.  

Most likely, Moderna will start with hematopoietic stem cells, which is the company’s bread-and-butter delivery method.

Now, just who, or what, could Moderna buy?

The news that the famed biotech is on the hunt comes a few months after Intellia reported successful first-in-human results for a transthyretin (ATTR) amyloidosis therapy. RBC Capital Markets analyst Lucca Issi pointed out in a Thursday afternoon note to clients that Moderna’s chitchat about its business development plans sent a ripple through Intellia’s stock.

Intellia’s shares—already strapped to a rocket ship thanks to the trial results in June—were hovering around the $140 range Thursday morning. The shares opened Friday at $168.

Other companies working on gene editing include CRISPR Therapeutics, Precision Biosciences, Beam Therapeutics and Sangamo Therapeutics.

https://www.fiercebiotech.com/biotech/moderna-ready-to-spend-covid-19-cash-and-famed-biotech-looking-for-a-gene-editor

Sanofi, Regeneron stop Libtayo-chemo lung cancer trial early on strong survival data

It's often a bad sign when a clinical trial stops early. Not so for Sanofi and Regeneron Pharmaceuticals. On Thursday, the partners said they were pumping the brakes on a pivotal study of a Libtayo-chemotherapy combo in lung cancer because the initial results were just that good. 

Sanofi and Regeneron signaled the early end to their phase 3 Libtayo trial in advanced non-small cell lung cancer (NSCLC) based on the study's independent data monitoring committee's recommendation after a prespecified interim analysis. The companies now plan to use the data for approval filings in Europe and the U.S.

Back in February, Libtayo broke into the highly competitive lung cancer market when the FDA approved the PD-1 inhibitor as a monotherapy for patients with newly diagnosed, locally advanced or metastatic NSCLC whose tumors have high levels of PD-L1 expression. The results released today are from the Empower-Lung 3 study, which is also in first-line patients but those with any level of PD-L1 expression and combined Libtayo and chemotherapy. Libtayo on top of platinum-doublet chemotherapy significantly improved overall survival versus chemotherapy in these patients.

The February green light put Libtayo on a collision course with Merck & Co.’s immunology superstar Keytruda. At the time of Libtayo’s lung cancer nod, SVB Leerink analyst Geoffrey Porges forecasted less than $1 billion in Libtayo peak sales in the disease, though he hinted that a future combo regimen could improve the drug's prospects.

Solo immuno-oncology drugs are currently only given to patients who can't tolerate chemo, and standard of care has pivoted to Keytruda plus chemotherapy. In the Keynote-407 study, which looked at a Keytruda-chemo combo regimen in squamous NSCLC, Keytruda cut death risk by 36% over chemo alone at an interim analysis. That reduction fell to 29% at final analysis. For its part, Libtayo’s Empower Lung-3 study is assessing the drug in patients with both squamous and non-squamous disease.

In nonsquamous NSLC, Keytruda plus chemo has demonstrated an impressive 51% reduction in death over chemo alone at interim analysis.

The interim analysis of the 466-patient Empower-Lung 3 trial showed the Libtayo-chemo combo slashed the risk of death by 29% versus chemotherapy alone. Median overall survival for patients on the Libtayo regimen was 22 months, compared to 13 months in the chemotherapy-alone cohort.

Notably, the phase 3 assessed the drug in patients with myriad tough-to-treat disease characteristics, Miranda Gogishvili, M.D., an oncologist and trial investigator, said in a statement.

Over the course of the 108-week study, patients received an infusion of either placebo or Libtayo 350mg every three weeks, plus platinum-doublet chemotherapy administered every three weeks for four cycles. On top of the overall survival endpoint, the study looked at progression-free survival as a coprimary endpoint and assessed secondary endpoints like objective response rate and best overall response.

Prior to the drug's lung cancer nod in February, Libtayo was confined to the realm of skin cancer. Its NSCLC monotherapy nod marked an important step on the drug's potential path toward blockbuster sales, but an approval for a combo regimen could be the real clincher. 

Aside from its lung cancer nod, Libtayo also won the FDA's blessing to treat basal cell carcinoma in February. Sanofi and Regeneron are also angling for a win in cervical cancer, where Libtayo solo was recently shown to slash the risk of death by 31% over chemotherapy in recurrent or metastatic cervical cancer that had progressed on platinum-based chemo.

https://www.fiercepharma.com/pharma/sanofi-regeneron-stop-libtayo-chemo-lung-cancer-trial-early-strong-survival-data

FDA approves Sanofi's Pompe disease treatment

 The U.S. Food and Drug Administration on Friday approved French drugmaker Sanofi's drug, Nexviazyme, for the treatment of patients with Pompe disease, a rare genetic disorder.

The health regulator allowed for the enzyme replacement therapy to be used in patients one year and older, and with late onset of the disease.

Pompe disease, which affects 1 in 40,000 people in the United States, is characterized by the build up of a complex sugar called glycogen in skeletal and heart muscles, which could lead to premature death.

Nexviazyme, developed by unit Sanofi Genzyme, intends to reduce the accumulation of glycogen.

https://finance.yahoo.com/news/u-fda-approves-sanofis-pompe-145134099.html

Nautilus Biotechology Up on CNBC Report About Amazon Investment

 Nautilus Biotechnology Inc. shares were recently up 13% to $8.46 after CNBC reported that Amazon.com Inc. had invested in the company.

Amazon had previously disclosed the investment in a Form 13F filing.

Nautilus was briefly paused due to volatility several times Thursday. The life sciences company is focused on technology "for quantifying and unlocking the complexity of the proteome."

https://www.marketscreener.com/quote/stock/NAUTILUS-BIOTECHNOLOGY-I-123640055/news/Nautilus-Biotechology-Up-13-on-CNBC-Report-About-Amazon-Investment-36084596/

Takeda Revises Lower First-Quarter Net Profit on Tax Provision

 Takeda Pharmaceutical Co. said Friday that it has revised lower its first-quarter net profit to Y137.68 billion ($1.25 billion) from Y200.38 billion previously, as it booked a provision for a potential tax payment.

The Japanese drug maker said earlier this week that it would book a Y63 billion provision related to potential taxes on a fee received by Shire PLC., which Takeda acquired in January 2019, following a decision by Irish Tax Appeals Commission.

In November 2018, Shire received a EUR398 million ($471 million) tax assessment from Irish Revenue Commissioners on a $1.635 billion fee that AbbVie Inc. paid to terminate an offer to buy Shire.

Takeda said earlier this week that the appeals commission upheld the revenue commissioners' position and that the Japanese drug maker intended to challenge the outcome through legal means.

https://www.marketscreener.com/quote/stock/TAKEDA-PHARMACEUTICAL-COM-6491073/news/Takeda-Pharmaceutical-Revises-Lower-First-Quarter-Net-Profit-on-Tax-Provision-36089233/