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

Editor’s Note

There has been an unusual high number of approvals and recommendations of drugs, vaccines, devices and diagnostics during this week, indicating that the innovation process is not slowing down in the first part of 2017.

Business

Merck KGaA enters an alliance with Avillion (London, UK), a drug development company, to develop its anti IL-17 A/F nanobody, which it acquired from Ablynx (Ghent/Zwijnaarde, Belgium) back in 2017 as a treatment for plaque psoriasis. Under this innovative business model, Avillion will be responsible for developing the product from phase 2 through phase 3 and Merck will take over the commercialisation of the approved therapy. Financial terms of the deal were not disclosed.

Merck & Co and Incyte (Wilmington, DL, USA) extend their collaboration to tackle a vast range of cancers in taking the combination of Keytruda, a check point inhibitor, and epacadostat, an indoleamine 2,3-dioxygenase (IDO1) inhibitor, through seven phase 3 pivotal trials. The combination, already successful in a melanoma trial, will be tested against non-small cell lung can­cer, blad­der can­cer, renal can­cer and squa­mous cell car­ci­noma of the head and neck (SCCHN).

Ono Pharmaceutical (Osaka, Japan) enters a collaboration with Numab Therapeutics (Pfäffikon, Switzerland), a company specialising in multispecific antibodies, to discover and develop new immuno-oncology products that could be combined with Opdivo. Under the terms of the deal Ono will pay up to ~$260 million plus royalties on sales.

Bristol-Myers Squibb enters a collaboration with Parker Institute for Cancer Immunotherapy, a non-profit organization set by Facebook’s Sean Parker, and the Cancer Research Institute (CRI) to expand its immuno-oncology footprint. Parker In­sti­tute indicated that these arrange­ments are in­tended to ac­cel­er­ate early re­search work and iden­tify promis­ing new ap­proaches and will remain out of commercialization.  Specific terms of the deal were not disclosed.

Novartis enters a multiyear partnership with Cota Healthcare to improve clinical outcomes for breast cancer patients. Novartis will tap Cota Healthcare’s web-based analysis and visualization tools, to accelerate the development of new breast cancer treatments and to identify the patients who would benefit most. Cota’s platform is based on its Cota Nodal Address technology, which uses personal and clinical information to classify patients into different groups. Patients in the same group may be considered medically identical, and so, should have similar treatments and similar outcomes.  The new deal builds is an extension of on a previous collaboration with a similar objective.

…and licenses two Phase 2 aging-related drugs to ResTORbio, a subsidiary of PureTech Health (Boston, MA, USA)   The two drugs are targeting rapamycyn complex 1 (mTORC-1) mechanisms as potential treatments for age-related deterioration in immune functioning. PureTech Health will make several milestones payments and pay royalties on sales and Novartis will gain an equity stake in ResTORbio.

Sanofi returns the rights it had acquired to erectile dysfunction drug STENDRA of avanifil to Vivus (Campbell, CA, USA) in African the Middle East, Turkey and the Commonwealth of Independent States (CIS or Russian Commonwealth) including Russia.

MedyMatch (Tel Aviv, Israel) has entered a deal to integrate its artificial intelligence-based decision-support technology with Samsung’s medical imaging machines in prehospital settings. Both companies will first focus on improving early stroke assessment in emergency vehicles by equipping them with Samsung NeuroLogica CereTom diagnostic CT imaging. Earlier this month, MedyMatch has entered a partnership with IBM Watson to integrate its IA applications into IBM Watson Health Imaging’s offerings. In 2016, MedyMatch, partnered with Capital Health to apply artificial intelligence to the analysis of stroke patients' medical images.

Novo A/S, a fully owned subsidiary of the Novo Nordisk Foundation, announces plans to acquire a 19.95% stake in ConvaTec (Reading, UK), once a division of Bristol-Myers Squibb for around for £1.01 billion. ConvaTec, a medical and technology company is specializing in areas of advanced wound care, ostomy care, continence and critical care and infusion devices used in the treatment of diabetes and other chronic conditions. Under the deal, Novo will also obtain the right to appoint one director to the ConvaTec Board.

Approval of drugs and vaccines

The European Commission has approved Pfizer’s Xeljanz, or tofacitinib citrate, an oral Janus kinase (JAK) inhibitor, in combination with methotrexate (MTX), as a treatment of moderate-to-severe active rheumatoid arthritis of patients who are intolerant to other disease modifying antirheumatic drugs (DMARDs). Xeljang can also be given as a monotherapy to patients who are intolerant to MTX or when MTX is inappropriate. Back in 2013, the European Medicine Agency's Committee for Medicinal Products for Human Use (CHMP)  did not recommend the drug's approval for RA, on grounds that it "did not believe that a consistent reduction in disease activity and structural damage to joints had been sufficiently demonstrated". Rheumatoid arthritis affects around 18 million people worldwide and around 3 million in Europe.

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended the approval of six new medicines:

Aperion Biologics’ (San Antonio, TX, USA) Dinutuximab beta Apeiron or dinutuximab beta, for the treatment of high risk forms of neuroblastoma, a rare cancer arising from neural crest cells, which are involved in the foetal development of the nervous system and other tissue. The drug is already used in Europe under a managed access programme as part of treatment regimens for high-risk forms of the disease.

Novo Nordisk’s Refixia or nonacog beta pegol, for the treatment and prevention of bleeding in patients with haemophilia B, a congenital factor IX deficiency

Bene–Arzeimittel’s (Munich, Germany) Elmiron, or pentosane polysulfate sodium, for the treatment of bladder pain syndrome characterized by either glomerulations or Hunner’s lesion.

Pfizer’s Trumenba, a meningococcal group B vaccine to prevent invasive meningococcal disease.

Blue Earth Diagnostics’ (Oxford, UK) Axumin, or fluciclovine [18F], for the detection of recurrence of prostate cancer with positron emission tomography (PET) imaging. The diagnostic is able to assess “with high sensitivity” the sites where prostate cancer has reappeared in patients after primary curative treatment of the prostate gland.

Accord Healthcare’s (Durham, NC, USA) Ivabradine, a procoralan generic version, first approved in the EU in 2005, for the treatment of angina pectoris and chronic heart failure.

The US FDA approves:

Roche’s Ocrevus or ocrelizumab, a first-in-class B cell targeted therapy, as a treatment for aggressive forms of multiple sclerosis (MS) and will be competing with Rebif, the standard of care for various forms of MS. In a rather unsual move, Roche priced this drug for mar­ket pen­e­tra­tion at $65,000 a year, a 25% dis­count to Rebif. (see below under Cost, Pricing and Market Access).

Sanofi and Regeneron Pharmaceutical’s Dupixent or dupilumab as a treatment of moderate-to-severe- atopic dermatitis (AD).  Dupilumab is a human monoclonal antibody which inhibits both interleukin- 4 (IL-4) and interleukin-13 (IL-13) two proteins underlying inflammation in AD.  The drug had received a priority review status back in September 2016 and is the first new treatment in years for AD.

Tesaro’s (Waltham, MA, USA) Zejula, or niraparib, a PARP inhibitor, as a maintenance treatment of epithelial ovarian, fallopian tube or primary peritoneal cancer after platinum chemotherapy. The drug will be competing with recently approved drugs with a similar mode of action such as AstraZeneca’s Lynparza and Clovis Oncology’s Rubraca. “Zejula is the first PARP inhibitor to be approved by the FDA that does not require BRCA mutation or other biomarker testing,” Tesaro said, adding that it’s also “the only PARP inhibitor that has demonstrated a clinically meaningful increase in progression-free survival (PFS) in women with recurrent ovarian cancer, regardless of BRCA mutation or biomarker status.”

….and Shionogi (Osaka, Japan) with partner Purdue Pharmaceuticals’ (Florham Park, NJ, USA and Stamford, Conn, USA) Symproic, or naldemedine, a peripherally–selective μ-opioid receptor antagonist,  closely related to naltrexone, as a treatment of patients with opioid-induced constipation who have chronic noncancer pain.

The China FDA (CFDA) approves AstraZeneca’s Tagrisso or osimertinib, as a treatment of patients with advances/metastatic epidermal growth factor receptor (EGFR) T790 M mutation positive non-small cell lung cancer whose disease has progressed on or after EGFR tyrosine kinase inhibitor therapy. The drug had been approved by the US FDA for this indication in November 2015 under an accelerated process and in Europe and Japan in Q1 2016.

Drugs at clinical stage

The European Medicine Agency grants orphan status:

To GW Pharmaceuticals’ (London, UK) Epidiolex’s, a cannabinoid drug, as a treatment of Lennox-Gastaut Syndrome (LGS), a rare an severe form of childhood-onset epilepsy.

…and to AstraZeneca’s ineblizumab, or MEDI6551 for the treatment of neuromyelitis optica spectrum disorder (NMOSD) a rare, life-threatening autoimmune disease of the central nervous system in which the body’s immune system attacks healthy cells, most commonly in the optic nerves and spinal cord, resulting in severe damage.

The US FDA grants:

Breakthrough status to Genentech’s Rituxan, or rituximab, as a treatment of phemphigus vulgaris, the rare and life-threatening autoimmune disorder causing progressive painful blistering of the skin and mucous membranes.

Fast-track status to ReveraGen BioPharma’s (Rockville, Maryland, USA) vamorolone or VBP15 as a treatment for Duchenne’s muscular dystrophy.

Orphan status to Opko Pharmaceuticals (Miami, FL, USA) CUR-1916, an oligonucleotide-based anti-natural antisense transcript to treat Dravet syndrome, a severe myoclonic epilepsy of infancy caused by defects in the SCN1A genes required for the proper function of brain cells. Children with Dravet Syndrome begin to decline in their development at age two, resulting in weakened mental and motor skills.

Priority review to Novartis’ CTL019 or tisagenlecleucel-T, as the first chimeric antigen receptor T cell (CAR-T) therapy for relapsed and refractory paediatric and young adult patients with B (cell acute lymphoblastic leukemia (ALL)

…and to Eagle Pharmaceuticals’ (Woodcliff, NJ, USA) Ryanodex, or dantrolene sodium, a muscle relaxant, as a treatment for patients with external heatstroke.

The China FDA approves FibroGen’s (San Francisco, CA, USA) CTA for a phase 2/3 study assessing roxadustat, an orally active small molecule inhibitor of hypoxia-inducible factor (HIF) prolyl hydroxylase, in non-transfusion dependent lower risk myeolodysplastic syndrome (MDS) patients with anemia. FibroGen collaborates with AstraZeneca in China, in the US and other major markets.

Janssen Biotech, a fully owned subsidiary of Johnson & Johnson and partner Genmab (Copenhagen, Denmark) will not proceed to stage two with daratumab monotherapy. The data review showed that two cohorts of the study, investigating the use of the drug in relapsed or refractory patients with follicular lymphoma (FL), and with diffuse large B-cell lymphoma (DLBCL) did not reach the predefined futility thresholds of overall response rates (ORR) of 50%, and 30%, respectively. Other on­go­ing and planned stud­ies with dara­tu­mumab in lym­phomas and other can­cers out­side mul­ti­ple myeloma will con­tinue as planned.

Medical Devices and Diagnosis News.

The US FDA approves

Qiagen’s (Hilden, Germany) Ipsogen JAK2 RGQ real-time PCR kit for the diagnosis of the blood cancer polycythemia vera, as the only FDA cleared assay for this mutation found in almost all patients with this disease. The Ipsogen JAK2 RGQ test is already approved in Europe.

Myriad Genetic’s (Salt Lake City, UT, USA) BRAC analysis complementary diagnostic test to identify ovarian cancer patients with germline BRCA mutations who are likely to benefit from Tesaro’s Zejula or niraparib, just approved PARP inhibitor. A companion diagnostic, according to the FDA, is necessary for the safe and effective use of a drug, and when a drug is approved with such a test, the label generally mentions its availability.

iCAD’s (Nashua, NH, USA) artificial intelligence-based solution that facilitates the interpretation of breast tomosynthesis, or 3D mammograms, and decreases the amount of time it takes a radiologist to read the images. Unlike two-dimensional mammography, which generates four images of the breasts, tomosynthesis can produce hundreds of images and provides a more complete picture. iCAD’s PowerLook Tomo Detection is a computer-aided detection solution for tomosynthesis. It uses a detection algorithm to pinpoint areas of interest on tomosynthesis images and combines them in a single image.

…and 510 (K) clearance to Bovie Medical’s (Puchase, NY, USA) J-Plasma generator and handpiece, as a more precise way to perform procedures with the more powerful monopolar coagulation approach. Monopolar coagulation, like J-Plasma, is a radiofrequency-based approach to surgery. By pairing a generator to an active electrode built into a handheld instrument, monopolar electrosurgical devices deliver electric current to coagulate blood.

Cost, Pricing and Market Access

The UK National Institute for Health and Care Excellence (NICE) has published a final guidance rejecting Shire’s Onivyde, a pegylated liposomal irinotecan, cleared by European Authorities in October 2016, as a routine treatment of pancreatic cancer. The Committee concluded that the overall pricing for pegylated liposomal irinotecan plus 5-fluorouracil (5-FU) and Leucoverin (LV) compared with 5-FU plus LV was over £100,000 per quality-adjusted life year (QALY) gained, and thus well outside the realm of what is considered value for money for the NHS.

Roche prices its newly approved OCREVUS as a treatment for various forms of multiple sclerosis at $65,000 a year, a 25% dis­count to Merck KGaA’s Rebif. “Ac­cord­ing to the NMSS, MS med­i­cines on av­er­age cost al­most 4 times more today than they did 12 years ago,” notes a spokesper­son for Roche. “In fact, Rebif – the 14 year-old stan­dard of care that OCRE­VUS was shown to be clin­i­cally su­pe­rior in two RMS tri­als – now costs about $86,000. We feel that the in­dus­try needs to start to re­verse this trend, and be­lieve that pric­ing Ocre­vus 25% less than the com­para­tor in our tri­als is an im­por­tant first step.” Merck rapidly replied to Roche’s Ocrevus' 25% discount on Rebif, calling a “direct comparison” between pricing for the drugs  “misleading and oversimplified. Ocrevus and Rebif have different modes of administration, they will typically be managed separately by payers and, therefore, the access and pricing approaches are different," a spokeswoman said in a statement. For its part, Roche said Ocrevus was “shown to be clinically superior” to the “14-year-old standard of care” Rebif in two relapsing multiple sclerosis trials

Miscellaneous

IQWIG, Germany’s healthcare cost watchdog, is continuing to push back against the European Medicines Agency’s (EMA) plans to accelerate the approval of new medicines. The German institute worries fast-track drug approvals based on limited clinical trial data or real-world evidence will become the norm—and that this will undermine attempts to fully evaluate the true safety and efficacy of medicines.

The US FBI has warned healthcare organizations of cybercriminals targeting unsecured servers to launch coordinated cyberattacks and use stolen patient information to blackmail providers  Allowing anonymous access to File Transfer Protocol (FTP) servers commonly used to transfer data has left healthcare institutions vulnerable to criminals that access protected health information (PHI) and personally identifiable information (PII) “for the purposes of intimidating, harassing, and blackmailing business owners,” according to a private industry notification (PDF) issued by the FBI.

US President Donald Trump wants to generate over $2bn from pharmaceutical company user fees to help fund the US FDA, according to his 2018 budget blueprint released by the Washington Post. He will also request $69 billion for the department of Health and Human Services, a 17.1% decrease on 2017 funding. As for the US National Health Institutes for Health (NIH) the Trump administration made three proposal consisting in a cut of $5.8 billion (20%) in fiscal year 2018 and $1.2 billion during the remainder of fiscal 2017 which end in October.

The US FDA nominee Scott Gottlieb is lined up at a Senate confirmation hearing on April 5. Democratic attacks are expected on the process Gottlieb has started to unwind its numerous business relationships and investments in as many as twenty different drug companies over the last ten years.

GlaxoSmithKline invests $175 million in its Marburg (Germany) facility, acquired from Novartis, to increase the production of Bexsero, its meningococcal B vaccine, currently produced at tea Sandoz site in Kundl (Austria).

People on the move

Alexion (New Haven, Conn, USA) appoints former Baxalta chief Ludwig Hantson as the new CEO and take the reins from David Brennan who acted as interim CEO after David Hallal left the company in December 2016.

In spite of receiving a US FDA priority review for CTL019 or tisagenlecleucel-T, as the first chimeric antigen receptor T cell (CAR-T) therapy, Karen Walker, the current VP Global Head Cell and Gene Ther­a­pies Tech­ni­cal De­vel­op­ment and Man­u­fac­tur­ing at No­var­tis, one of three se­nior executive put in charge of the cell and gene ther­apy ini­tia­tive, is leaving the company to join Seattle Genetics (Seattle, WA, USA) as Vice President of Global Quality.

Bioevents

BIOVISION on April 4-6, in Lyon (France)

Strategic Alliance Management Congress on May 1-3, in Philadelphia (USA)

BIOTrinity on May 8-10, in London (UK)

China BIO Partnering Forum on May 10-11 in Suzhou (China)

9^th Annual China BIO International Partnering Forum on May 31-June 1 in Zhuhai (China)

The Health Industry Sumitt (tHIS) 2017 on May 15-18 in Shanghai (China)

2017 BIO-IT World Conference & Expo on May 23-25 in Boston (USA)

BIO International Convention on June 19-22 in San Diego (USA)

MedFIT on June 28-29 in Grenoble (France)

Nordic Life Science Days (NLS) 2017 on September 12-14 in Malmö-Copenhagen (Sweden and Denmark)

BIOPharm America on September 26-27 in Boston (USA)

BIO Latin America on October 26-28 in Sao Paulo (Brazil)

BIO Europe on November 6-8 in Berlin (Germany)

World Congress on Biomedical Engineering 2017 on November 9-11 in Xian (China)

BIOFIT on November 28-29 in Strasbourg (France)

http://btobioinnovation.com/events/pharma-biotech-events/

http://btobioinnovation.com/events/in-vitro-diagnostic-events/

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