Author: Jean-Claude Muller, 穆卓Executive Editor at BtoBioInnovation,  jcm@btobioinnovation.com

Zika virus

The French Regional Health Agency (ARS) reports the death of the first Zika virus victim, a man 84 years old, in Martinique (France) where 19 patients with a Guillain-Barré syndrome have been identified.

The World Health Organization (WHO) is stating that the Zika virus is likely to spread to parts of Europe this summer although with a low to moderate likelihood of an outbreak. Areas most at risk include the Black Sea coast of Russia and Georgia and the island of Madeira.  Countries with a moderate risk include France, Spain, Italy and Greece, while the threat in Germany and the UK is low.

The US Senate approves President Obama’s emergency funding to combat the Zika virus in passing a first comprise measure of $1.1 billion.

Innovio Pharmaceuticals (Plymouth Meeting, PA, USA) announced that its candidate synthetic DNA vaccine against Zika virus elicited “robust” antibody and T cell responses in monkeys. “With positive large animal results in hand we are moving aggressively to initiate and conduct our first Zika vaccine human trial in 2016,” said Inovio CEO Joseph Kim.

Acquisitions /mergers/joint-ventures

Pfizer acquires Anacor Pharmaceuticals (Palo Alto, CA, USA) for 5.2 billion in an all cash deal. Anacor is the exclusive US distributor of Sandoz's PharmaDerm's Kerydin tavaborole) topical solution 5%, the first oxaborole antifungal indicated for the treatment of onychomycosis (toenail fungal infection). But Anacor’s lead product candidate is crisaborole topical ointment, a PDE4 inhibitor, for the treatment of atopic dermatitis, with a PDUFA date of January 7, 2017. According to Pfizer, the drug could achieve or exceed peak sales of more than $2 billion a year, given its performance in Phase 3.

Fosun Pharmaceuticlas (Shanghai, China) is in the race to acquire unlisted Gland Pharma (Hyderabad, India) joining Baxter International and Advent International at a value around $1.5 billion.

Mylan acquires Renaissance Acquistion Holdings’ (Longueil, Canada) dermatological product portfolio for $950 million. Under the terms of the deal Myan will add about 25 branded and generic non-sterile topical products. Renaissance, majority owned by private equity firm RoundTable Healthcare Partners, will retain its sterile-focused businesses and associated manufacturing facility.

Siemens Healthcare now rebranded Siemens Healthineers acquires Neo New Oncology (Erlangen, Germany) to expand its molecular diagnostics offering. Neo has a liquid biopsy test called NeoLiquid, which is "uniquely able to detect all therapeutically relevant point mutations, small insertions and deletions, translocations and copy number changes.Specifically, it identifies clinically relevant, cancer-specific point mutations, insertions, deletions and gene fusions in circulating cell-free DNA down to an allele frequency of 0.1%. It can also detect copy number alterations in circulating tumor DNA. Financial terms of the deal were not disclosed.

Business

Janssen Biotech, a division of Johnson & Johnson, enters into a collaboration and license agreement with MacroGenics (Rockville, MD, USA) to develop new immunotherapies for treatment of various cancers. Under the terms of the agreement Janssen Biotech will get a license agreement for MGD 015, a preclinical bispecific molecule which incorporates MacroGenic’s proprietary Dual-Affinity Re-Targeting, or DART® platform, to simultaneously target CD3 and an undisclosed tumor target for the potential treatment of various hematological malignancies and solid tumors. Janssen Biotech will pay a $75 million upfront fee and up to $665 million in clinical, regulatory and commercialization milestones payments as well as double-digit royalties. Both companies had inked a first partnership at the end of 2014 when J&J paid $125 million for rights to MGD011, a CD19/CD3 drug for B-cell malignancies.

Johnson & Johnson partners with HP to use 3-D printing to improve healthcare outcomes. Both companies will focus on personalization of instrumentation and software for patient-specific healthcare devices in areas such as orthopedics, eye health and consumer products.

Celgene collaborates with Agios Pharmaceuticals (Cambridge, MA, USA) on the discovery and the development of metabolic immune-oncology treatments, based on Agios cellular metabolism technology, in a deal worth up to $1 billion. Under the terms of the agreement Celgene gets the right to designate collaboration programs with an option fee of $30 million eligible and up to $169 million in clinical and regulatory milestones. In case the collaboration generates any inflammation or autoimmune programs, Celgene has the option to enter into an exclusive worldwide license agreement and pay up to $386 million in clinical, regulatory and commercial milestone payments, as well as double-digit tiered royalties on any net sales. Both companies also agreed to amend a collaboration first signed in 2010, with Agios regaining full rights to AG-120, an oral inhibitor of mutant isocitrate dehydrogenase 1.

Horizon Pharma (Dublin, Ireland) has licensed rights to interferon gamme-1b from Boehringer Ingelheim in around 30 countries in Europe and the Middle East for $25 million. In a separate agreement, Horizon negotiated US, European and Canadian rights for interferon gamma-1b for the treatment of Friedreich's ataxia from an undisclosed third party.

Biogen (Cambridge, MA, USA) partners with University of Pennsylvania on a gene therapy development targeting the eye, skeletal muscle and central nervous system. Both partners will seek to validate next-generation gene transfer technology using adeno-associated virus (AAV) gene delivery vectors, as well as explore expanded use of genome editing technology as a potential therapeutic platform. Under the terms of the agreement Biogen will pay $20 million upfront, and an additional $62.5 million to fund R&D costs over the next 3–5 years in seven distinct preclinical R&D programs. Each program may trigger milestones that range from $77.5 million to $137.5 million per product as well as royalties payable on net sales of products.

BGI (Shenzhen, China), the world largest omics organization, collaborates with Clearbridge Biomedics, a National University of Singapore spinoff, to bring the ClearCell^® FX1 solution, a liquid biopsy testing, into the market in China. The ClearCell^® technology is a label-free, automated system that is able to isolate and enrich intact, viable rare cells from a patient’s blood sample.

Approval of drugs and vaccines

The European Commission approves:

Biogen and Swedish Orphan Biovitrium’s (Stockholm, Sweden) Alprolix, a recombinant coagulation factor IX fusion protein; for patients with hemophilia B. The drug which is already approved in several countries including the US, is indicated for both on-demand and prophylactic treatment of people with the condition.

….and Actelion’s (Allschwil, Switzerland) Uptravi (selexipag), a selective prostacyclin receptor agonist, as a new treatment option to patients with pulmonary arterial hypertension. The drug was approved by the US FDA in December 2015.

US FDA approves:

Eisai’s (Tokyo, Japan) Lenvima, or lenvitanib, a tyrosine mTOR inhibitor, in combination with Novartis’ Erolimus for the treatment of renal cell carcinoma, the most common form of kidney cancer. Lenvima was already approved in the US for patients with locally recurrent or metastatic, progressive, radioactive iodine-refractory differentiated thyroid cancer.

Bristol-Myers Squibb’s Opdivo, for the treatment of classical Hodgkin lymphoma. This is the eighth approval for Opdivo in less than two years in four distinct cancer types, encompassing three solid tumours and now expanding to a haematologic malignancy.

US FDA grants an accelerated approval to Genentech’s Tecentriq, or atezolizumab, the first PD-L1 checkpoint inhibitor for the treatment of advanced or metastatic urothelial carcinoma, a specific bladder cancer for which no new drug has been approved in more than 30 years. Tecentriq had received “breakthrough” status from the US FDA for lung cancer last month.

….as well as a PD-L1 biomarker developed by Roche Diagnostics

Drugs at clinical stage

US FDA grants breakthrough status to Celator Pharmaceuticals’ (Ewing, NJ, USA) Vyxeos, or cytarabine/daunorubicin as a treatment for acute myeloid leukemia with myelodysplasia-related changes.

US FDA grants fast-track status to KemPharm’s (Coralville, Iowa, USA) investigational hydromorphone candidate, KP511, which is being developed as an extended-release prodrug to manage severe pain.

AstraZeneca’s benralizumab, an interleukin5 (IL-5) inhibitor, successfully achieved its primary endpoint in two Phase 3 trails demonstrating reductions in the annual asthma exacerbation rate versus placebo.

…..But AstraZeneca’s Lymparza, in combination with paclitaxel, failed to achieve its primary endpoint in overall survival when compared to paclitaxel alone, in Asian patients with advanced gastric cancer. The GOLD study, was conducted in China, Japan, South Korea and Taiwan, in 525 Asian patients with advanced HER2-negative gastric. The incidence of gastric cancer in East Asia is 9 time higher than in western countries. Lymparza is approved in over 40 including the US where it is approved for patients with BRCA-mutated advanced ovarian cancer.

Medical Devices and Diagnosis News

US FDA grants Siemens Healthineers the first approval for a 3-D only digital breast tomosynthesis system. The use of 3-D is expected to decrease patient recall rates and result in a lower radiation dose. The Mammomat Inspiration with Tomosynthesis Option digital mammography system also increases cancer detection compared to 2-D alone.  "Although this is the first breast tomosynthesis solution on the market to demonstrate statistically superior results to 2-D as a stand-alone breast exam, we know many providers will continue using 3-D tomosynthesis as an adjunct to 2-D screenings” said Martin Silverman, VP of X-ray Products at Siemens Healthineers.

US FDA approves Biofrontera’s (Leverkusen, Germany) Ameluz and RhodoLED medical device to treat mild to moderate actinic keratosis of the face and the scalp which is caused by ultraviolet radiation. Ameluz gel contains a photo-activated compound called 5-aminolaevulinic acid applied to the keratosis lesions, then exposed after 3 hours to the red light from the BF-RhodoLED lamp, which causes the 5-aminolaevulinic acid to react with oxygen to create a toxic type of oxygen that kills the cancer cells. Biofrontera won CE Mark approval in the European Union for Ameluz in 2011 and followed up with BF-RhodoLED CE Marking in 2012.

Novartis’ inhaler Ultibro Breezhaler is superior to GlaxoSmithKline’s Seretide on reducing COPD flare-ups. The FLAME study, which involved 3,362 COPD patients, showed that once-daily treatment with Ultibro Breezhaler (indacaterol/glycopyrronium bromide) was non-inferior to twice daily Seretide (salmeterol/fluticasone) in reducing exacerbations.  The findings also showed Novartis’ drug to be superior to the widely used inhaled corticosteroid (ICS)/LABA combination, considered the standard of care.

Science and Technology

Combining metformin with insulin in the treatment of Type 2 diabetes has been found to reduce the risk of mortality, according to a new study by a team from Cardiff University. The population of people receiving insulin in combination with metformin may be healthier than the monotherapy group. And for patients getting insulin alone, the researchers found that those prescribed high-dose insulin were at a 28% increased risk for all-cause mortality versus those getting low-dose insulin.

A recent study from Washington University has shown that stem cells programmed to act as insulin-secreting beta cells could become a treatment of Type 1 diabetes.

Islexa, a joint venture between The Cell and Gene Therapy Catapult and the University of Aberdeen (Scotland) are developing a technology of growing and converting pancreatic tissue into fully functional pancreatic islets to enable more Type 1 diabetes to receive transplants. Current techniques are limited due to rejection, cell dying during transplantation and shortage of donors islets.

Cost, Pricing and Market Access

National Institute for Healthcare and Care Excellence (NICE) rejects Roche’s Perjeta, pertuzumab, to treat certain forms of breast cancer. “Taking all the uncertainties around the clinical effectiveness of pertuzumab into account, as well as uncertainties with the economic data presented by the company, the committee concluded that it could not recommend the drug for the treatment of HER2-positive breast cancer before surgery as a good use of NHS resources,” said Sir Andrew Dillon, NICE chief executive. The UK cancer charities have written an open letter to the Premier Minister David Cameron – published in The Daily Telegraph – warning that plans to leave the appraisal methodology employed by the NICE unchanged will soon lead to effective new cancer medicines struggling to gain approval. Breast Cancer Now chief executive, Baroness Delyth Morgan, said: “Not a single breast cancer drug has been considered cost-effective by NICE in the last seven years and this simply cannot continue. The voices of patients are, at best, not being heard, and, at worst, being ignored. With an anachronistic NICE system still unable to engage in price negotiation, it’s inevitable that patients will not be able to access the clinically-proven medicines that could mean so much to them,” she warned, and said it is “high time” for a review of the system.

China’s National Health and Family Planning Commission today reported it had reduced the price of AstraZeneca's lung cancer drug Iressa by more than half to 7,000 yuan ($1,069) from 15,000 ($2,292). It also reduced the price of Gliead’s Viread hepatitis B drug that GSK sells in China by about two-thirds, to 490 yuan a month from 1,500 as well as China's Betta Pharmaceuticals’ lung cancer drug Icotinib which price was reduced to 5,500 from 12,000 yuan a month. According to a recent Bloomberg report, Chinese citizens pay up to 77% of all private healthcare costs compared to the U.S., where consumers pay 22%.

According to a note from Deutsche Bank, drug prices in the US increased by 5% through April 2016, compared to 7.8% for the same period in 2015 with Valeant having the most significant change in pricing behavior. The company list price increased by 1.2% in January to April 2016 versus 25.8% change during the same period last year. List price growth for other large US drugmakers also decreased in early 2016 with an average list price increase through April 2016 of 3.5%, compared with 4.0% for the same period last year. The analysis was only based on list prices and does not factor in rebates or discounts that go into final pricing.

Miscellaneous

Novartis has announced plans to divide its current pharmaceutical division into two business units named Novartis Pharmaceuticals and Novartis Oncology forming the Innovative Medicine Division and sees the departure of current division head and CEO David Epstein to “explore new challenges from the US”. Paul Hudson, currently executive vice president, North America, at AstraZeneca, will lead Novartis Pharmaceuticals; and Bruno Strigini, currently head of Novartis’ oncology segment, will lead the new Novartis Oncology business unit.

Fermion, a subsidiary of Orion Corporation (Espoo, Finland), will invest €30 million to expand its API (active pharmaceutical ingredient) facility in Hanko (Finland) to build its classified high potency or Occupational Exposure Banding 5 (OEB5) products which requires containment level of 0.1µg/m3

The former chairman of Goldman Sachs Asset management, Lord Jim O’Neil has put forward a proposal to the UK Government to offer a price of $1 billion to drug makers that come up with new antibiotics once they have been approved for use. O’Neill suggests allocating a small percentage of G-20 existing health care spending to tackling that, along with reallocating a fraction of global funding from international institutions to antimicrobial resistance (AMR). Other proposals were to impose a charge on pharmaceutical companies that don’t invest in research in AMR and to put a tax on antibiotics. At the World Economic Forum in Davos earlier this year, a coalition of 85 companies in the pharmaceutical, diagnostic, biotech and generic sectors signed the Declaration on Combating Antimicrobial Resistance (see Biopharmaceutical Newsweek #2016.3)

Bioevents

4^th Annual IBA World Life Sciences Conference on June 3-4 in San Francisco (USA)

ASCO Annual Meeting on June 3-6 in Chicago (USA)

BIO International Convention on June 6-9 in San Francisco (USA)

APinnov on June 14 in Paris (France)

BIO Pharm America on September 13-15 in Boston (USA)

7^th Innovation Days on October 3-4 in Paris (France)

BIO Europe on November 7-9 in Cologne (Germany)

BIO Latam on November 29-30 in San Juan (Puerto Rico)

Biofit 2016 on November 30-December 1 in Lille (France)

IMPORTANT NOTICE

This document has been prepared by btobioinnovation and is provided to you for information purposes only.  The information contained in this document has been obtained from sources that btobioinnovation believes are reliable but btobioinnovation does not warrant that it is accurate or complete. The views presented in this document are those of btobioinnovation’s editor at the time of writing and are subject to change.  btobioinnovation has no obligation to update its opinions or the information in this document.