Astellas New Data on XOSPATA in Acute Myeloid Leukemia at Hematology Meet

Emerging mutations in patients with treatment resistance, from Phase 3 ADMIRAL study, will be focus of oral presentation

Astellas Pharma Inc. (TSE: 4503, President and CEO: Kenji Yasukawa, Ph.D., “Astellas”) today announced the presentation of new data in acute myeloid leukemia (AML) at the 61^st American Society of Hematology (ASH) Annual Meeting, taking place Dec. 7-10 in Orlando, Fla.

Seven abstracts sponsored by Astellas focus on patients with relapsed (disease that has returned) or refractory (resistant to treatment) AML with a FLT3 mutation (FLT3mut+). The abstracts include new findings from the Phase 3 ADMIRAL trial – an oral presentation on emerging mutations in patients who develop resistance after an initial response to XOSPATA and two poster presentations focused on patient-reported outcomes – as well as data on cost-effectiveness, FLT3 testing and treatment patterns, and venetoclax combination therapy.

https://www.biospace.com/article/releases/astellas-presents-new-data-on-xospata-gilteritinib-in-flt3-mutation-positive-relapsed-refractory-acute-myeloid-leukemia-at-the-2019-american-society-of-hematology-annual-meeting/

Astellas to buy Audentes for $3 billion in high-priced gene therapy bet

Japan’s Astellas Pharma Inc is buying U.S. drugmaker Audentes Therapeutics Inc for about $3 billion in cash, in a high-priced push to make genetic medicines a key area of growth.

Gene therapies are one of the hottest areas of drug research and Astellas, Japan’s second-largest drugmaker by sales, is offering $60 per share for San Francisco-based Audentes, a 110% premium to its closing price on Monday.

Citi analyst Hidemaru Yamaguchi said that while the deal looked expensive, it was a positive move for Astellas as Audentes had “cutting-edge gene therapy modalities”.

“We thought it was only a matter of time before Astellas entered the gene therapy market,” he wrote in a note for clients, adding it had already licensed development rights for a domestic gene therapy in Amyotrophic lateral sclerosis (ALS).

Gene therapies aim to cure diseases by replacing the missing or mutated version of a gene found in a patient’s cells with healthy copies. With the potential to cure devastating illnesses in a single dose, drugmakers say they justify prices well above $1 million per patient.

“As a result of this acquisition, Astellas will obtain not only Audentes programs but also it’s proprietary manufacturing knowhow in gene therapy,” Astellas CFO Naoki Okamura told a briefing in Tokyo. “Internal manufacturing capability is a great strength for companies with multiple programs under development.”

Genetic drugs will become a fifth primary focus for Astellas, Okamura said, joining existing business lines in regenerative, immuno-oncology, immunotherapy, and neuro-muscular medicine.

The acquisition marks the second biggest on record for Astellas after its 2010 purchase of OSI Pharmaceuticals Inc for$3.8 billion, according to Refinitiv data. Astellas expects the deal, which is subject to regulatory approval including U.S. antitrust clearance, to close in the first quarter of 2020.

Audentes’ investigational drug, AT132, is being developed to treat a rare genetic neuromuscular disorder which results in extreme muscle weakness, respiratory failure and in some cases early death.

Astellas said the companies plan to seek FDA approval for AT312 in mid-2020. The drug has shown promising results in the treatment of X-linked myotubular myopathy (XLMTM) seen mainly in male infants, it said.

Only about 40 boys are born in the United States with the condition each year, so that would yield just $80 million in revenue, said Jefferies analyst Stephen Barker, assuming a maximum price tag for the treatment.

“The $3 billion acquisition price is therefore more likely to be mainly predicated on the firm’s technology platform and manufacturing capabilities,” Barker wrote in a note.

The deal also marks the latest consolidation in the industry which saw Japan’s Takeda Pharmaceutical Co Ltd acquire Britain’s Shire for $59 billion.

Shares in Astellas fell 1.1% on Tuesday in Tokyo, underperforming a 0.6% decline in the broader market <.N225>.

The stock’s decline was “the natural reaction”, said Credit Suisse analyst Fumiyoshi Sakai.

“This is a difficult deal to digest because it deals with gene therapy,” Sakai said. “They have to be very square with the investment community about what they’re buying.”

Morgan Stanley & Co LLC, is Astellas’ financial adviser while Covington & Burling LLP is the company’s legal counsel.

Centerview Partners LLC is acting as financial adviser to Audentes and Fenwick & West LLP is its legal counsel.

https://www.marketscreener.com/ASTELLAS-PHARMA-INC-6491262/news/Japan-s-Astellas-to-buy-Audentes-for-3-billion-in-high-priced-gene-therapy-bet-29671205/

AstraZeneca Sells Seroquel Rights to Cheplapharm

AstraZeneca PLC (AZN.LN) said Tuesday that it has agreed to sell the commercial rights to the drugs Seroquel and Seroquel XR in the U.S. and Canada to Cheplapharm Arzneimittel GmbH for an upfront payment of $35 million.

The U.K. pharmaceutical company said that as well as the upfront payment, there may also be future sales-contingent payments of up to $6 million.

The company said the agreement doesn’t impact the company’s financial guidance for 2019 and that the agreement became effective upon signing.

“This divestment supports our strategy of reducing the number of mature medicines to enable reinvestment in our main therapy areas,” said Ruud Dobber, executive vice president of the biopharmaceuticals business unit.

https://www.marketscreener.com/ASTRAZENECA-4000930/news/AstraZeneca-Sells-Seroquel-Rights-to-Cheplapharm-29672338/

New treatment for brain tumors uses electrospun fiber

A novel engineering process can deliver a safe and effective dose of medicine for brain tumors without exposing patients to toxic side effects from traditional chemotherapy.

University of Cincinnati professor Andrew Steckl, working with researchers from Johns Hopkins University, developed a new treatment for glioblastoma multiforme, or GBM, an aggressive form of brain cancer. Steckl’s Nanoelectronics Laboratory applied an industrial fabrication process called coaxial electrospinning to form drug-containing membranes.

The treatment is implanted directly into the part of the brain where the tumor is surgically removed.

The study was published in Nature Scientific Reports.

“Chemotherapy essentially is whole-body treatment. The treatment has to get through the blood-brain barrier, which means the whole-body dose you get must be much higher,” Steckl said. “This can be dangerous and have toxic side-effects.”

Steckl is an Ohio Eminent Scholar and professor of electrical engineering in UC’s College of Engineering and Applied Science.

Coaxial electrospinning combines two or more materials into a fine fiber composed of a core of one material surrounded by a sheath of another. This fabrication process allows researchers to take advantage of the unique properties of each material to deliver a potent dose of medicine immediately or over time.

“By selecting the base materials of the fiber and the thickness of the sheath, we can control the rate at which these drugs are released,” Steckl said.

The electrospun fibers can rapidly release one drug for short-term treatment such as pain relief or antibiotics while an additional drug or drugs such as chemotherapy is released over a longer period, he said.

“We can produce a very sophisticated drug-release profile,” Steckl said.

The breakthrough is a continuation of work conducted by research partners and co-authors Dr. Henry Brem and Betty Tyler at Johns Hopkins University, who in 2003 developed a locally administered wafer treatment for brain tumors called Gliadel.

Unlike previous treatments, electrospun fibers provide a more uniform dose over time, said UC research associate Daewoo Han, the study’s lead author.

“For the current treatment, most drugs release within a week, but our discs presented the release for up to 150 days,” he said.

Glioblastoma multiforme is a common and extremely aggressive brain cancer and is responsible for more than half of all primary brain tumors, according to the American Cancer Society. Each year more than 240,000 people around the world die from brain cancer.

The electrospun fiber created for the study provided a tablet-like disk that increased the amount of medicine that could be applied, lowered the initial burst release and enhanced the sustainability of the drug release over time, the study found.

Chemotherapy using electrospun fiber improved survival rates in three separate animal trials that examined safety, toxicity, membrane degradation and efficacy.

“This represents a promising evolution for the current treatment of GBM,” the study concluded.

While this study used a single drug, researchers noted that one advantage of electrospinning is the ability to dispense multiple drugs sequentially over a long-term release. The latest cancer treatments rely on a multiple-drug approach to prevent drug resistance and improve efficacy.

Steckl said the study holds promise for treatments of other types of cancer.

“Looking ahead, we are planning to investigate ‘cocktail’ therapy where multiple drugs for the combined treatment of difficult cancers are incorporated and released either simultaneously or sequentially from our fiber membranes,” Steckl said.

https://www.eurekalert.org/pub_releases/2019-12/uoc-ntf120219.php

Aslan’s Rally Grows After Positive Readout From Eczema Drug Study

After soaring 81.25% Wednesday and augmenting the gains by an incremental 65% Friday, ASLAN PHARMACEU/ADR ASLN 36.13% shares were  accelerating further Monday morning.

The stock has seen  strong upward momentum since late November.

Atopic Dermatitis Drug Data

Singapore-based Aslan, which has its ADSs listed on the Nasdaq, announced positive data Monday from the lowest-dose cohort of its ongoing multiple dose study of ASLAN004, which is being evaluated for moderate-to-severe atopic dermatitis.

ASLAN004 is a fully human monoclonal antibody that binds to the IL-13 receptor α1 subunit, which in turn blocks signalling of two pro-inflammatory cytokines, IL-4 and IL-14. These two cytokines are responsible for the triggering of symptoms of atopic dermatitis such as redness and itching of skin, according to the company.

The Eczema Area and Severity Index scores of of three patients who completed one month of dosing were reduced by 85%, 70% and 59% from the baseline, with the EASI score continuing to drop, Aslan said.

The company said it expects maximum efficacy at six to eight weeks.

The investigational compound was well-tolerated, with no serious adverse events or treatment discontinuations observed, according to the company.

Aslan’s Target Market

Atopic dermatitis, a severe form of eczema, affects more than 200 million people worldwide, severely impairing their quality of life.

About one-third of adult atopic dermatitis are characterized as moderate to severe, and there are only limited treatment options, according to Aslan.

“We are pleased to report encouraging preliminary data from this study of ASLAN004. Whilst the data remains early, we had not anticipated to observe such pronounced improvements in patients enrolled into the lowest dose cohort,” said Dr. Mark McHale, the biotech’s head of R&D.

The data monitoring committee will meet in late December, after which Aslan said it plans to open the second dose cohort. The company expects to release interim results in early 2020, with the completion of the study expected in the second half of 2020.

https://www.benzinga.com/general/biotech/19/12/14911534/aslans-rally-grows-after-positive-readout-from-eczema-drug-study

Galera Has Novel Radiation Oncology Pipeline; Commercialization Looms

Galera Therapeutics Inc (NASDAQ: GRTX), a biopharma company that is working on novel therapeutics for transforming radiotherapy treatment in cancer, recently IPO’d, offering 5 million shares at $12 apiece.

Following the expiry of the IPO quiet period, Citigroup analyst Yigal Nochomovitz initiated coverage of Galera with a Buy rating and $20 price target.

Credit Suisse analyst Evan Seigerman initiated coverage of the shares with a Neutral rating and $14 price target.

New Player with a Novel Approach In Radiation Oncology Market

Galera has demonstrated very good proof-of-concept Phase 2b data for lead drug GC4419 in the prevention of severe oral mucositis – a radiation side effect common in head and neck cancer, Nochomovitz said in a note.

The analyst assigned a 80% probability of the FDA approving GC4419 for he indication, with the pipeline asset most likely to become standard-of-care.

Nochomovitz also expects positive readthrough for GC4419 in a second indication – esophagitis in lung cancer.

“We see potential upside for second asset GC4711 if initial proof-of-concept data in locally-advanced pancreatic cancer (LAPC) are positive,” Citi said in the note.

The firm estimates peak risk-adjusted revenues of $370 million for oral mucositis, $200 million for esophagitis and $9 million for LAPC.

Commercialization Faces Significant Challenges

Galera’s lead asset GC4419, an intravenous administered, small molecule dismutase mimetic currently in Phase 3 development for oral mucositis, addresses an unmet need with differentiated efficacy, but there are likely to be headwinds to broad commercialization due to pipeline competition and logistical challenges, Seigerman said.

The analyst expects the pivotal Phase 3 data from the ROMAN study to be positive, supporting approval by 2023. Commercial launch is likely by 2023, with the asset estimated to rake in unadjusted peak sales of over $200 million by 2025.

With GC4419 required to be administered as a 60-minute infusion immediately prior to radiation, the analyst sees only a limited number of facilities as capable of offering the IV infusion as well as radiation.

“We see a favorable risk/reward for the early pipeline for esophagitis and anti-cancer efficacy improvement, but the path to commercialization remains unclear, Credit Suisse wrote in the note.

Therefore, the firm said it is assigning no value to indications outside of oral mucositis, although it sees upside to its forecast stemming from pipeline progress.

https://www.benzinga.com/analyst-ratings/analyst-color/19/12/14913617/analysts-galera-has-novel-pipeline-for-radiation-oncology-market-commercialization-

Olaparib first gene-targeted medicine to show benefits in prostate cancer

A pioneering precision medicine already licensed for breast and ovarian cancer can also slow or stop tumour growth in some men with advanced prostate cancer, a new clinical trial shows.

The phase II trial found that over 80 per cent of men with prostate cancer whose tumours had mutations in the BRCA genes responded well to treatment with the targeted drug olaparib.

Men in the study had already received chemotherapy and their disease was advanced. Patients treated with olaparib whose prostate cancers had DNA repair defects lived for more than 13 months on average – and nearly 18 months among those with BRCA mutations – raising the prospect that it could become the first ever gene-targeted drug to be approved for prostate cancer.

The TOPARP-B trial was led by a team at The Institute of Cancer Research, London, and The Royal Marsden NHS Foundation Trust. It is published in The Lancet Oncology today (Friday) and was funded in part by olaparib’s manufacturer, AstraZeneca, plus by Cancer Research UK, Prostate Cancer UK, the Prostate Cancer Foundation, Movember and the Experimental Cancer Medicine Centre (ECMC) Network.

An initial trial, TOPARP-A, tested use of olaparib in a group of men with advanced prostate cancer who weren’t selected for treatment based on gene mutations, and suggested that those whose tumours had mutations in a range of genes involved in repairing damage to DNA could benefit most.

That led to TOPARP-B, which was the first study to direct olaparib specifically at men whose prostate cancers had mutations in their DNA repair systems. The researchers used olaparib to treat 98 men, at 17 UK hospitals, with mutations in DNA repair genes, and who all had advanced cancer which had been heavily pre-treated. Overall, they found that 47 per cent of men with these DNA repair defects responded to olaparib, halting disease progression for an average of 5.5 months.

The most common DNA repair defects were mutations in the BRCA1 and BRCA2 genes, but various other mutations were also detected including those in the PALB2, ATM and CDK12 genes.

Men with BRCA mutations responded best to olaparib, with more than 80 per cent responding and 40 per cent remaining free of disease progression for more than a year. Additionally, over half of patients carrying PALB2 mutations responded to olaparib, as well as 37 per cent of those with ATM mutations. Some 20 per cent of patients with other DNA repair gene alterations also responded to olaparib.

The median overall survival with olaparib was 17.7 months for patients with BRCA mutations, compared with 16.6 for men with ATM mutations, and 13.9 months for those with PALB2 mutations.

Olaparib is one of a class of drugs called PARP inhibitors which are licensed for women with ovarian and breast cancer who have mutations in the BRCA genes. Scientists at The Institute of Cancer Research (ICR) were the first to discover how to genetically target olaparib, and they went on to develop the drug in clinical trials with colleagues at The Royal Marsden.

The researchers believe men with advanced prostate cancer should now routinely have their tumours tested for DNA repair defects such as BRCA mutations, so that where appropriate they can benefit from PARP inhibitors.

The ICR is seeking to discover novel gene-targeted medicines and innovative ways of combining them within its pioneering new Centre for Cancer Drug Discovery – a £75 million investment focused on finding new ‘anti-evolution’ treatments that can overcome drug resistance.

Study leader Professor Johann de Bono, Regius Professor of Cancer Research at The Institute of Cancer Research, London, and Consultant Medical Oncologist at The Royal Marsden NHS Foundation Trust, said:

“Our trial has shown that men with prostate cancer who were selected for faults in DNA repair genes responded very well to the targeted drug olaparib, especially where they had BRCA mutations in their tumours.

“This study and another phase III trial place olaparib on the verge of becoming the first genetically targeted treatment in prostate cancer. I’m excited by these findings, and keen to see further research assessing how we can combine olaparib with other treatments to extend patients’ lives even more dramatically.”

Professor Paul Workman, Chief Executive at The Institute of Cancer Research, London, said:

“Precision medicines targeted to specific genetic faults are transforming treatment for many different cancers, and with this new research it looks like we will soon be able to add prostate cancer to that list. It’s exciting to see a drug which the ICR helped pioneer having such widespread benefits for both women and men with cancer.

“The next step is to work out how to combine olaparib with other drugs to keep cancer at bay for much longer. That’s the kind of research we will be carrying out in our new Centre for Cancer Drug Discovery, which aims to create innovative new treatments designed to overcome cancer evolution and drug resistance.”

https://www.eurekalert.org/pub_releases/2019-12/iocr-obf112919.php