Asklepios BioPharmaceutical launches new portfolio company Actus Therapeutics

Published 15 December 2017

Asklepios BioPharmaceutical has formed Actus Therapeutics, a new portfolio company based on AskBio’s industry-leading gene therapy platform.

Actus will benefit from AskBio’s ability to generate organ and tissue-specific single-stranded and self-complementary genome containing adeno-associated virus vectors (AAVs), the company’s manufacturing platform and managements’ experience progressing AAV gene therapy programs into the clinic. Actus will pursue therapies for multiple rare genetic diseases, and will initially focus on developing a gene therapy for Pompe Disease based on the research of Dwight Koeberl, M.D., Ph.D., professor of pediatrics and a medical genetics specialist at Duke University.

“AskBio is focused on expanding our current gene therapy portfolio to help patients and families with rare genetic diseases that might be treated through our proprietary gene-therapy platform,” said Sheila Mikhail, President and CEO of AskBio and Actus.

“We continue to advance the efficacy of our vectors as well as our manufacturing platform, and we are excited to be working with Dr. Dwight Koeberl and his team at Duke, with the aim of developing a new therapy for Pompe Disease.”

Actus will create targeted low-dose gene therapies for orphan diseases using AskBio’s AAV platform technologies and manufacturing process. AskBio’s AAVs are effective at lower doses, have increased cell-type specificity and have the potential for reduced systemic side-effects.

 AskBio’s proprietary manufacturing technology has been proven to be more efficient than other manufacturing technologies and has been used in clinical-grade GMP and preclinical-grade GLP manufacturing campaigns as well as several thousand research-grade lots.

“We have shown in mice that AAV gene therapies have the potential to overcome the limitations of enzyme replacement therapy by delivering low doses and restricting expression to the liver,” said Dr. Dwight Koeberl, “We look forward to working with Actus and bringing these therapies into human clinical trials. We are currently recruiting patients for an FDA-approved Phase I trial and hope to be underway early next year.”

Actus is currently recruiting 20 adult patients with late-onset Pompe Disease for the clinical trial.

Pompe Disease is a genetic disease caused by the deficiency of acid-alpha-glucosidase (GAA) in muscle, resulting in the accumulation of glycogen in organs and tissues, especially muscles, which can impair their ability to function normally. While enzyme replacement has shown promise in infantile-onset Pompe patients, no curative therapy is available.

Source: Company Press Release

FDA approves Pfizer’s Xeljanz and Xeljanz XR to treat active psoriatic arthritis

Published 15 December 2017

The US Food and Drug Administration (FDA) has approved Pfizer’s Xeljanz 5 mg twice daily (BID) and Xeljanz XR (tofacitinib) extended release 11 mg once daily (QD) for the treatment of adult patients with active psoriatic arthritis (PsA) who have had an inadequate response or intolerance to methotrexate or other disease-modifying antirheumatic drugs (DMARDs).

XELJANZ/XELJANZ XR is the first and only Janus kinase (JAK) inhibitor approved by the FDA for both moderate to severe rheumatoid arthritis (RA) and active PsA.

“Psoriatic arthritis is a complex and progressive disease with an unpredictable course,” said Angela Hwang, Global President, Inflammation and Immunology, Pfizer. “The approval of XELJANZ is an important step forward for patients seeking new treatments and is a testament to Pfizer’s unwavering commitment to advancing patient care.”

The recommended dose of XELJANZ/XELJANZ XR is in combination with nonbiologic DMARDs, and use in combination with biologic DMARDs or with potent immunosuppressants such as azathioprine and cyclosporine is not recommended.

The FDA approval of XELJANZ for the treatment of adult patients with active PsA was based on data from the Phase 3 Oral Psoriatic Arthritis Trial (OPAL) clinical development program, which consisted of two pivotal studies, OPAL Broaden and OPAL Beyond, as well as available data from an ongoing long-term extension trial, OPAL Balance. The findings from OPAL Broaden and OPAL Beyond were published in October 2017 in the New England Journal of Medicine.

Both pivotal studies met their two primary efficacy endpoints, demonstrating statistically significant improvements in American College of Rheumatology 20 (ACR20) response and change from baseline in the Health Assessment Questionnaire–Disability Index (HAQ-DI) score at three months in patients receiving XELJANZ 5 mg BID treatment in combination with a nonbiologic DMARD, compared to those treated with placebo.

In OPAL Broaden, 50% of patients taking XELJANZ 5 mg BID achieved an ACR20 response, compared to 33% of patients taking placebo (p≤0.05), at three months. In OPAL Beyond, 50% of patients achieved an ACR20 response with XELJANZ 5 mg BID, compared to 24% of patients taking placebo (p≤0.05), at three months.

In both studies, statistically significant improvements in ACR20 response was also seen with XELJANZ 5 mg BID compared to placebo at week 2, a secondary endpoint and the first post-baseline assessment (OPAL Broaden: 22% and 6% [p=0.0003], respectively; OPAL Beyond: 27% and 13% [p=0.0046], respectively).

“As a practicing rheumatologist, I’ve seen the significant physical impact psoriatic arthritis has on people living with the disease, and many patients are looking for additional therapeutic options,” said Philip Mease, M.D., Swedish Medical Center, University of Washington and study investigator. “I’m pleased that XELJANZ is now available for use in the treatment of this chronic condition.”

The safety profile observed in patients with active psoriatic arthritis treated with XELJANZ was consistent with the safety profile observed in rheumatoid arthritis patients. The most common adverse events observed occurring in greater than 3% of patients on XELJANZ 5 mg BID were nasopharyngitis, upper respiratory tract infection, headache and diarrhea. Please see Important Safety Information below.

“Psoriatic arthritis is a serious and debilitating chronic illness that should be diagnosed and treated early,” said Randy Beranek, president and CEO, National Psoriasis Foundation. “As an organization that advocates for people living with psoriatic arthritis, we welcome the availability of new therapies for treating this disease.”

Source: Company Press Release

Drugmaker Teva to cut 14,000 jobs globally

PBR Staff Writer Published 15 December 2017

Teva Pharmaceutical Industries said it will lay off 14,000 jobs globally as part of a two-year restructuring plan, aimed at boosting its business and financial performance.

The reductions in jobs, which will be carried out over the next two years, represent over 25% of the company’s total workforce.

Teva’s restructuring plan aims to cut down its total cost base by $3bn by the end of 2019, out of an estimated cost base of $16.1bn for the current year.

The company is looking to lay off over 7,000 employees by the end of next year.

Teva anticipates at least $700m of restructuring charge which will be mainly linked to severance costs.

The company is also expecting additional charges relating to closures or sale of manufacturing plants, research and development facilities, headquarters and others.

Teva president and CEO Kåre Schultz said: “We will execute this plan in a timely and prudent manner, remaining focused on revenue and cash flow generation, in order to make sure Teva is ready to meet all of its financial commitments.

“Teva will optimize its cost base while ensuring that we protect our revenues and preserve our core capabilities in generics and in select specialty assets, in order to secure long-term growth. In 2018, we expect to secure the successful launches of Austedo and fremanezumab.”

The pharmaceutical company also plans to optimize its global generics portfolio substantially, particularly in the US by making price adjustments and possibly discontinue certain products.

Teva believes that the steps would allow it to speed up the restructuring of its manufacturing and supply network which includes closures or sales of several manufacturing plants in the US, Israel, Europe and others.

Teva is looking to make 1,700 employees redundant by the end of 2019 along with the closure of a manufacturing plant in Jerusalem, reported The Times Of Israel.

Image: Teva Canada Centre of Excellence for Penicillin Products – Address: 575 Hood Road, markham, Ontario. Photo: courtesy of Raysonho @ Open Grid Scheduler / Grid Engine.

Flexion Therapeutics to acquire novel and non-opioid asset for osteoarthritis of knee

Published 14 December 2017

Flexion Therapeutics has entered into a definitive agreement with GeneQuine Biotherapeutics GmbH to acquire the global rights to GQ-203.

As part of the agreement, Flexion obtained an exclusive license to the underlying intellectual property rights for human use of GQ-203 from Baylor College of Medicine. GQ-203, now known as FX201, is a preclinical, non-opioid, intra-articular therapeutic being developed for symptomatic pain relief and disease modification in patients with osteoarthritis (OA) of the knee.

As part of the deal, Flexion will make an upfront payment of $2 million to GeneQuine and may incur milestone payments of up to $8.7 million through Phase 2 proof of concept (PoC). Following successful PoC, Flexion may incur up to $54 million in future development and global regulatory approval milestone payments, with Baylor also receiving a low single-digit royalty on net sales of FX201.

After taking into account Flexion’s payment obligations in connection with the acquisition and the anticipated preclinical and clinical development costs for FX201, the company still expects current cash to bring Flexion to profitability.

FX201 is a locally administered gene therapy designed to stimulate the production of an anti-inflammatory protein, interleukin-1 receptor antagonist (IL-1Ra), whenever inflammation is present within the joint.

Inflammation is a known cause of pain, and chronic inflammation is thought to play a major role in the progression of OA. By persistently suppressing inflammation, FX201 may both reduce pain and modify the disease.

“We believe FX201 could represent a next-generation therapeutic approach for OA, and it supports our long-term objective of having a pipeline of high-quality drug candidates that are positioned to enter the market as ZILRETTATM matures,” said Michael Clayman, M.D., President and Chief Executive Officer of Flexion.

 “With its potential to deliver an unprecedented duration of pain relief and possibly arrest the progression of disease, FX201 could transform the treatment of OA, while fitting nicely within our commercial infrastructure.”

Based on strong preclinical data, a single injection of FX201 could potentially enable expression of IL-1Ra in an osteoarthritic joint for a least a year. Initially, FX201 will be targeted towards a subpopulation of patients who confront aggressive OA of the knee and would be expected to differentially benefit from this therapy.

Flexion expects to hold a pre-Investigational New Drug meeting with the U.S. Food and Drug Administration in the first half of 2018, and pending successful results from preclinical studies, the company aims to initiate a Phase 1 clinical trial in 2019.

OA is the most common joint disease, affecting more than 30 million Americans and accounting for more than $185 billion in annual expenditures. In 2016, more than 15 million Americans were diagnosed with OA of the knee and the average age of physician-diagnosed knee OA has fallen by 16 years, from 72 in the 1990s to 56 in the 2010s.

The prevalence of OA is expected to continue to increase as a result of aging, obesity and sports injuries. Each year, more than 15 million Americans are treated for OA-related knee pain, and approximately five million OA patients receive either an immediate-release corticosteroid or hyaluronic acid intra-articular injection to manage their knee pain.

Source: Company Press Release

GW Pharmaceuticals reacquires full rights of develop Sativex in US

Published 14 December 2017

GW Pharmaceuticals has terminated its previous license agreement with Otsuka Pharmaceutical in relation to Sativex (nabiximols) in the US.

As a result, GW has now reacquired full ownership of the development and commercialization rights to the product in the U.S. market without making any upfront payment to Otsuka.

GW has agreed to make contingent milestone payments to Otsuka, the first of which would become due upon FDA approval of Sativex and thereafter additional payments would become due upon the achievement of certain annual sales thresholds of Sativex in the United States.

“We are pleased to have amicably reached this agreement with Otsuka, which enables GW to develop, seek approval for, and commercialize Sativex in the United States,” stated Justin Gover, GW’s CEO.

“We have previously conducted several positive Phase 2 and 3 trials for Sativex and believe that this product represents an important new late-stage pipeline opportunity for GW in the U.S. market.”

Sativex is an oromucosal spray of a formulated extract that contains the principal cannabinoids cannabidiol (CBD) and delta-9-tetrahydrocannabinol (THC) in a 1:1 ratio. Sativex is currently approved in 29 countries outside the U.S. for the treatment of spasticity in patients with multiple sclerosis.

GW and Otsuka originally signed a licensing agreement in 2007 under which GW granted Otsuka an exclusive license to develop and market Sativex in the U.S. The two companies conducted a clinical trials program in the treatment of cancer pain, in which the trials did not meet the primary endpoint.

Source: Company Press Release

Pfizer's biosimilar of J&J's Remicade secures FDA approval

PBR Staff Writer Published 14 December 2017

Pfizer’s IXIFI (PF-06438179, infliximab-qbtx), a biosimilar to Johnson & Johnson’s rheumatoid arthritis drug Remicade (infliximab), has been approved by the US Food and Drug Administration (FDA) for all indications of the reference product.

IXIFI is a chimeric human-murine monoclonal antibody (mAb) against tumor necrosis factor.

The drug has now been indicated in the US for the treatment of patients having rheumatoid arthritis (RA), Crohn’s disease, pediatric Crohn’s disease, ankylosing spondylitis, psoriatic arthritis, ulcerative colitis and plaque psoriasis.

IXIFI’s approval is based on the totality of evidence showing a high degree of similarity to the reference product which includes the findings of the REFLECTIONS B537-02 study in patients with moderate to severe active RA.

The phase 3 REFLECTIONS B537-02 trial saw IXIFI evaluated in comparison to Remicade administered intravenously in combination with methotrexate to treat patients with moderate to severely active RA who did not show inadequate response to methotrexate therapy.

The late-stage study met its primary endpoint, defined to be ACR20 response (≥20% improvement by American College of Rheumatology criteria) at Week 14.

In February 2016, Sandoz, the generic pharmaceuticals arm of Novartis, acquired rights for the development, commercialization and manufacturing of IXIFI in the European Union along with Iceland, Liechtenstein and Norway.

As per the terms of the deal with Sandoz, Pfizer retains commercialization and manufacturing rights of its Remicade biosimilar in countries outside the European Economic Area (EEA).

Outside the US, Pfizer has a portfolio of three marketed biosimilar medicines which are Inflectra (infliximab), Retacrit (epoetin zeta), and Nivestim (filgrastim). Its biosimilars pipeline features 13 distinct biosimilar molecules in different stages of development. 

Pfizer, as part of its global biosimilars strategy, supplies Celltrion’s Inflectra (infliximab-dyyb) in the US and certain other markets across the world.

Image: Pfizer World Headquarters in Manhattan, New York pictured in 2016. Photo: courtesy of Coolcaesar/

Allergan acquires Repros Therapeutics

Published 13 December 2017

Repros Therapeutics has entered into a definitive agreement under which Allergan, through a subsidiary, will acquire Repros for a cash payment of $0.67 per share.

The Company’s Board of Directors has unanimously approved the transaction.  

Under the terms of the merger agreement, a subsidiary of Allergan will commence a cash tender offer to purchase all of the outstanding shares of Repros common stock for $0.67 per share.  The closing of the tender offer is subject to customary closing conditions, including the tender of a majority of the outstanding shares of Repros common stock. 

The merger agreement contemplates that Allergan, through its subsidiary, will acquire any shares of Repros that are not tendered into the offer through a second-step merger, which will be completed as soon as practicable following the closing of the tender offer.  Pending approvals, Repros anticipates the transaction will close during the first quarter of 2018.

Stifel, Nicolaus & Company, Incorporated is serving as exclusive financial advisor to Repros, and Morgan, Lewis & Bockius LLP is serving as Repros’ legal counsel. Covington & Burling LLP is serving as Allergan’s legal counsel.

Repros Therapeutics focuses on the development of small molecule drugs for major unmet medical needs that treat male and female reproductive disorders.

Source: Company Press Release

Shire gets EC nod for lyophilized Oncaspar to treat acute lymphoblastic leukemia

PBR Staff Writer Published 13 December 2017

Shire has secured marketing approval from the European Commission (EC) for new formulation of Oncaspar to treat patients with acute lymphoblastic leukemia (ALL).

The approval has been granted for lyophilized Oncaspar as a component of antineoplastic combination therapy to treat ALL in pediatric patients from birth to 18 years and adult patients.

The EC approval allows the company to market new treatment in 28 member states of the European Union (EU), in addition to Iceland, Liechtenstein and Norway.

In October this year, the European Medicines Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP) recommended lyophilized Oncaspar to treat ALL.

Through depleting serum L-asparagine levels and later interfering with protein synthesis, Oncaspar will divest lymphoblasts of L-asparagine to kill cells.

According to the company, Asparaginase is a crucial component of the treatment regimen for ALL patients, as it will induce leukemic cell death.

The company is planning to start the marketing of lyophilized Oncaspar from the first half of 2018.

Shire global research and development ad-interim head and SVP Dr Howard Mayer said: “This approval underscores Shire’s commitment to patients with acute lymphoblastic leukemia through continued research and evolution of asparaginase therapy.

“With this lyophilized formulation, we aim to make pegylated asparaginase, part of the pediatric standard therapy in acute lymphoblastic leukemia, available to patients in countries where liquid Oncaspar is not currently offered.

“Additionally, with extended shelf life up to 24 months, treatment centers will have flexibility in inventory management to help ensure continuous treatment supply for patients.”

CMC Biologics signs development and manufacturing deal with Harpoon Therapeutics

Published 13 December 2017

CMC ICOS Biologics and Harpoon Therapeutics have signed an agreement to develop and manufacture HPN424, HPN536, and HPN217, representing three TriTAC molecules for the treatment of several human cancers.

Harpoon Therapeutics’ TriTAC molecules are half-life extended and designed to simultaneously bind to cancer cells and T-cells, triggering those T-cells to attack the targeted cancer cells.

These molecules contain three binding domains: one domain binds a specific tumor target, the second domain binds to human serum albumin, and the third domain binds to T-cells.

Harpoon’s first clinical candidate, HPN424, a prostate-specific membrane antigen (PSMA)-targeting TriTAC, is in development for the treatment of metastatic prostate cancer and expected to enter Phase 1 clinical trials in 2018.

“We value our partnership with CMC Biologics as our CDMO for the development and manufacturing of our first wave of molecules entering the clinic,” said Gerald McMahon, Ph.D., President and CEO of Harpoon Therapeutics.

“CMC Biologics’ exceptional track record, expertise and guidance, and unique capability to ensure accuracy and quality will play a significant role in the successful production of our TriTAC molecules.”

“With great strides being taken daily in the discovery and development of new oncology treatments, we’re delighted to be working with Harpoon Therapeutics on these exciting new TriTAC molecules, enabling CMC Biologics to participate in the roll-out of transformative new treatments with the potential to significantly impact patient lives,” said Gustavo Mahler, PhD, Chief Executive Officer & President of CMC Biologics.

“Our advanced CHEF1 Expression Technology will facilitate production of high levels of recombinant protein in rapid time-frames, with a focus on an accelerated process, precise outputs, and excellence in service. We’re looking forward to working closely with Harpoon Therapeutics on this important endeavor.”

Source: Company Press Release

Combination of AbbVie's venetoclax and Rituxan succeeds in phase 3 R/R CLL trial

PBR Staff Writer Published 13 December 2017

AbbVie and Roche’s Venclexta/Venclyxto (venetoclax) in combination with MabThera/Rituxan (rituximab) succeeded in a phase 3 trial in patients with relapsed or refractory (R/R) chronic lymphocytic leukemia (CLL) by meeting the primary endpoint.

The late-stage study, dubbed MURANO, demonstrated that Venclexta/Venclyxto, an oral B-cell lymphoma-2 (BCL-2) inhibitor in combination with MabThera/Rituxan cut down the risk of disease progression or death by 83% in comparison to a standard of care regimen in previously treated CLL.

MURANO evaluated the AbbVie and Roche drug combination therapy against bendamustine in combination with MabThera/Rituxan in 389 patients who had one to three prior therapies.

Venclexta/Venclyxto in combination with MabThera/Rituxan was shown to have achieved significant median progression-free survival (PFS) compared with bendamustine in combination with MabThera/Rituxan.

The primary endpoint of the trial was investigator-assessed PFS while secondary endpoints were Independent Review Committee (IRC)-assessed PFS, PFS in patients with 17p deletion, best overall response, and nodular partial response [nPR] among others.

Roche chief medical officer and global product development head Sandra Horning said: “The MURANO study results indicate that Venclexta/Venclyxto plus MabThera/Rituxan has the potential to provide an important new chemotherapy-free option for people with previously treated chronic lymphocytic leukaemia.

“We are particularly encouraged by the magnitude of benefit observed across key efficacy measures compared to a current standard of care, and we look forward to discussing these results with health authorities.”

Venclexta/Venclyxto is jointly commercialized by AbbVie and Genentech, a subsidiary of Roche in the US. Outside of the US, the drug is commercialized by AbbVie.

AbbVie research and development executive vice president, and chief scientific officer Michael Severino said: “The data from the MURANO trial represents the next evolution in a potential treatment option for patients with relapsed/refractory CLL, an indication for which we received Breakthrough Therapy Designation.”

According to AbbVie, the findings from the MURANO trial also serve as the phase 3 confirmatory study asked by the US Food and Drug Administration (FDA) when Venclexta was given an accelerated approval in April 2016.

The company says that regulatory submissions of venclexta/venclyxto in combination with Rituxan to health authority are in progress.

Image: AbbVie Corporate Headquarters. Photo: courtesy of AbbVie Inc.