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

Mergers, Acquisitions and Joint Ventures

Takeda Pharmaceutical and PRA Health Sciences (Raleigh, NC, USA), a clinical CRO, establish a joint venture in Japan aimed at improving operating efficiencies and accelerate the “transformation” of its R&D organization. The change is a global effort that is looking to refocus R&D on targeted therapeutic areas and to concentrate R&D organization in Japan and the US.  As part of the new joint venture, Takeda will establish a new, wholly-owned subsidiary to be part of Takeda Development Center in Japan.

Business

AstraZeneca licenses US and Canadian commercial rights of Zoladex, or goserelin acetate implant, an injectable luteinising hormone-releasing hormone agonist, to TerSera Therapeutics (Celdar Rapids, IA, USA) as a treatment for prostate and breast cancer as well as certain gynecological disorders. Under the terms of the deal, TerSera will make a $250M payment at closing, milestones up to $70M and quarterly mid-teen royalties. AstraZeneca will manufacture and supply the product. In 2016, Zoladex generated $69M in sales in the US and Canada and $816M worldwide.

Valeant Pharmaceuticals has granted Swedish Orphan Biovitrum or SOBI (Stockholm, Sweden) exclusive rights and license for distribution and sales of Ammonul injection in the Middle East, North Africa and Europe. Ammonul, or sodium phenyl acetate and sodium benzoate, is indicated for the treatment of acute urea cycle disorders. Financial terms of the deal were not disclosed.

Clinerion (Basle, Switzerland) expands its Asian geographic activities through a partnership with ASUS Life (Taiwan) and will be able to recruit patients at eight hospitals in Taiwan in using Clinerion’s Patient Recruitment System.

Incyte (Wilmington, DL, USA) enters a collaboration with University of Pennsylvania’s Ambrason Cancer Center to study novel therapeutics being discovered at Incyte, with the goal of better understanding their mechanisms of action and developing clinical rationales for combination therapy and patient selection. Financial terms were not disclosed.

Boehringer Ingelheim partners with Weill Cornell Medicine’s Departement of Genetic Medicine (New York, USA) to identify new treatment approaches that could halt or reverse lung tissue damage in chronic obstructive pulmonary disease patients. This collaboration is the second collaboration between Boehringer Ingelheim and Weill Cornell Medicine, following prior work in inflammatory bowel disease.

Gilead Sciences acquires Sarepta Therapeutics’ (Cambridge, MA, USA) Rare Disease Priority Review Voucher (PRV) which it received from the US FDA for its Duchenne muscular dystrophy drug Exondys 51, or eteplirsen, last September for $125 million in an upfront payment. A PRV is designed to promote development of new drugs and biologics preventing and treating rare pediatric diseases. “The sale of the PRV provides an important source of nondilutive capital to support the rapid advancement of our follow-on exon-skipping candidates and next-generation RNA-targeted antisense platform,” Sarepta CEO Edward Kaye, M.D., said in a statement.

Merck is taking a $2.9 billion charge, or $1.9 billion after taxes, on uprifosbuvir or MK-3682, a hepatitis C drug which it accessed through its $3.9 billion acquisition of Idenix Pharmaceuticals in 2014. Merck indicated that it now values the drug at $240 million.

Approval of drugs and vaccines

The European Commission has approved Celltrion Healthcare’s Truxima (CT-P10) a rituximab biosimilar for the same autoimmune disease and cancer indication as the reference product. The approval makes Truximab the first biosimilar monclonal antibody toebe approved as a cancer treatment in the world, and Celtrion’s second biosimilar approved in Europe. Mundipharma is now gearing up to launch the drug in seven European markets. "Assuming the price of biosimilar rituximab is 70% compared to reference rituximab, and the market share of biosimilar rituximab is 30% (first year), 40% (second year) and 50% (third year), over this three-year time period the budget savings across the 28 countries of the EU would be around 570 million euros", said Professor László Gulácsi, head of Department of Health Economics, Corvinus University of Budapest.

The European Commission grants conditional approval to Roche and Chugai's Alecensa, or alectinib, as a monotherapy for ALK-positive advanced non-small-cell lung cancer (NSCLC) in adult patients who previously received crizotinib. Under terms of the conditional approval in Roche will have to provide additional data on first-line Alecensa therapy in ALK inhibitor naïve ALK-positive NSCLC patients from the ongoing Phase 3 study ALEX trial comparing Alecensa to crizotinib.

The European Medicine Committee for Medicinal Products for Human Use (CHMP) has recommended the approval of AstraZeneca’s ZS-9, as treatment of hyperkalemia.

US FDA approves Celgene’s Revlimid or lenalidomide as a maintenance drug for patients with multiple myeloma after autologous hematopoietic stem cell transplantation after two late-stage trials showed a significant increase in progression-free survival of patients compared with no maintenance treatment.

US FDA approval of Momenta Pharmaceuticals’ (Cambridge, MA, USA) Glatopa, a larger (40 mg) dose of glatiramer acetate injection a generic form of Teva’s copaxone will not happen as originally expected after the agency issued a warning letter to Pfizer’s contract business Centre One (former Hospira site) fill and finish facility in McPhesron (Kansas, USA). According to Manoj Garg of HealthCo Research, the plant received Form 483s in quarter one 2012, quarter two 2012, quarter three 2013, quarter four 2014, quarter two 2015, and most recently in quarter two 2016 after the inspection in May and June. “The situation at McPherson is even more concerning in that a $120 million modernization initiative was announced in June 2014 for that facility,” his note says.

Drugs at clinical stage

US FDA grants breakthrough therapy status to Tocagen’s (San Diego, CA, USA) drug combination Toca 511 and Toca FC an investigational combination product consisting of a biologic and a small molecule as a treatment for patients with recurrent high-grade glioma, one of the most common and aggressive forms of primary brain cancers.

US FDA grants priority review to Pfizer’s inotuzumab ozogamicin as treatment for relapsed or refractory B-cell precursor acute lymphoblastic leukemia (ALL). The product is an antibody-drug conjugate (ADC) consisting of a humanized mAb against CD22 linked to the calicheamicin cytotoxin which already has breakthrough status and Orphan Drug designations in the U.S. to treat ALL and Orphan Drug designation in the EU to treat B cell ALL. UCB and Pfizer are partnered on the product.

US FDA grants Fast Track designation to Vericel’s (Cambridge, MA,USA) Ixmyelocel-T,, for the treatment of advanced heart failure due to ischemic dilated cardiomyopathy. Ixmyelocel-T is an investigational autologous expanded multicellular therapy administered via transendocardial catheter-based injections, developed through Vericel's proprietary cell-processing system to selectively expand the population of mesenchymal stromal cells and activated macrophages from the patient's own bone marrow.

US FDA accepts Novartis’s supplemental New Drug Application (sNDA) for Zykadia or ceritinib under Priority for the treatment of first-line patients with metastatic ALK-positive non-small cell lung cancer (NSCLC). The drug is already approved to treat ALK-positive NSCLC patients who have been previously treated with Pfizer's Xalkori or crizotinib.

Roche confirms one patient death in the pivotal phase 3 study with emicizumab or ACE910 as a treatment for hemophilia. The in­ves­ti­ga­tor con­cluded that the pa­tient died as a re­sult of a rec­tal he­m­or­rhage and that Roche’s drug was not re­spon­si­ble. The re­port, though, raises fresh ques­tions about the drug’s safety after in­ves­ti­ga­tors had to fend off per­sis­tent ques­tions about four spon­ta­neously re­ported serious adverse events after two pa­tients had throm­boem­bolic events and two pa­tients de­vel­oped throm­botic mi­croan­giopa­thy.

AstraZeneca’s Lynparza, a PARP inhibitor hits its primary endpoints in the treatment of HER2-negative metastatic breast cancer who also carry BRCA1 or BRCA2 mutations in boosting progression-free survival (PFS). Lynparza is currently approved by regulatory health authorities in the EU for use as monotherapy for the maintenance treatment of adult patients with platinum-sensitive relapsed BRCA-mutated (germline and/or somatic) high grade serous epithelial ovarian, fallopian tube or primary peritoneal cancer who are in response (complete or partial) to platinum-based chemotherapy. It is also approved in the US as monotherapy in patients with deleterious or suspected deleterious germline BRCA-mutated advanced ovarian cancer who have been treated with three or more prior lines of chemotherapy.

Bayer and development partner Janssen R&D announced the successful outcome of COMPASS, a large-scale Phase 3 study involving 27,402 patients, that assessed the effect of blood thinner Xarelto  or rivaroxaban in preventing major adverse cardiac events. The trial was scheduled to finish next year but was stopped early on the advice of an independent Data Monitoring Committee, after the primary endpoint of prevention which includes cardiovascular death, myocardial infarction and stroke reached its pre-specified criteria for superiority over aspirin.  The drug could potentially be used on 30 million patients with coronary artery disease (CAD) and peripheral artery disease (PAD), in addition to the roughly 25 million patients it sees in the atrial fibrillation market, says Bayer. Xarelto is currently the only non-vitamin K antagonist oral anticoagulant (NOAC) currently under assessment in this high-risk patient population. The drug is already on the market for reducing the risk of stroke and blood clots.

Argos Therapeutics’ (Durham, NC, USA) rocapuldencel-T, a personalized cancer vaccine did not meet its primary endpoint according to the conclusion of an independent monitoring committee analysis. A similar technology, with activated “trained T cells” had previously been used by Argos to attack HIV and failed to reduce viral load in afflicted subjects.

Agenus (Lexington, MA, USA) says an in­de­pen­dent data mon­i­tor­ing com­mit­tee over­see­ing the Phase II com­bi­na­tion study of its can­cer vac­cine Prophage with Avastin (be­va­cizumab) found no en­cour­age­ment that the vac­cine — made of heat shock pro­tein-pep­tide com­plexes taken from a pa­tient’s tumor tis­sue — was any bet­ter than be­va­cizumab alone in pro­long­ing sur­vival among brain can­cer pa­tients.

Medical Devices and Diagnosis News.

General Electric (GE) Ventures enters a strategic alliance with the Feinstein Institute, the research arm of Northwell Health (New York, USA), to advance new bioelectronic therapies and diagnostics for a range of diseases. The alliance will support Feinstein’s Center for Bioelectronic Medicine (CBEM), which is targeting neurodegenerative disease, cancer, rheumatoid arthritis and diabetes, The pair’s new investment will drive basic and applied R&D, clinical development and the “advancement of systems and materials to support the application of new technologies. As bioelectronic treatments are identified and developed, the CBEM will promote the creation of new companies to commercialize them.

Immunexpress (Seattle, WA, USA) gets a US FDA 510 (k) clearance clearance for its RNA-based clinical diagnostic that detects sepsis in critically ill patients. The test, which uses whole blood, returns results in a few hours. Sepsis which is the result of an “overwhelming” immune response to infection and can lead to extensive inflammation, organ failure and death is one of the leading causes of death in the intensive care unit. Immunexpress’ SeptiCyte LAB differentiates between infection-positive systemic inflammation (sepsis) from infection-negative systemic inflammation, according to a statement. It is the first RNA-based clinical diagnostic tool that helps caregivers identify sepsis early, the company said. Current sepsis diagnosis is based on the detection of pathogens and can take multiple days. SeptiCyte measures molecular markers from the patient’s immune system rather than relying on the presence of a pathogen, the company said. This allows it to identify infection earlier, more quickly and more accurately than existing tests.

Cost, Pricing and Market Access

The UK National Institute for Health and Care Excellence:

Has endorsed Amicus Therapeutics’ (Cranbury, NJ, USA) Galafold, or migalastat, as an alternative treatment to injectable enzyme replacement therapies for Fabry disease, a rare genetic disorder, an inherited lysosomal storage disease caused by deficiency in the enzyme alpha-galactosidase A (alpha-gal A). Galafold is the first orally administered alternative to the Sanofi's Fabrazyme (agalsidase beta) and Shire's Replagal (agalsidase alfa), and works by stabilizing the body's own dysfunctional enzyme. The drug will be approved on the condition that Amicus provides an undisclosed discount to the drug's list price of £210,000 per patient per year.

Has issued final guidelines backing routine use of Novartis’s Afinitor, or everolimus, an active inhibitor of the mammalian target of rapamycin (mTOR) protein, a central regulator of tumour cell division and blood vessel growth in cancer cells, in certain patients with advanced kidney cancer. Novartis offered a discount on the drug's cost of £32,076 per patient, which helped secure its routine use. and the committee concluded that the most plausible Incremental cost-effectiveness ratio (ICER) for Afinitor compared with best supportive care would be less than £30,000 per quality-adjusted life year (QALY) gained

….and rejects Ipsen’s (Boulogne-Billancourt, France) Cabometyx in concluding that the additional benefits of the drug, when compared with current care, "were highly uncertain as the meta-analysis evidence presented by the company was unreliable”. The ICERs for cabozantinib compared with any comparator were calculated to overshoot the £30,000 per QALY gained, and thus outside the bounds of what is normally considered a cost effective use.

Miscellaneous

Denmark officially bids for the relocation of the European Medicines Agency (EMA). At least twenty other countries may wish to host the Agency. The intervention of the Japanese government in early September 2016 brought the EMA issue further into the open when a 15-page letter came up where Japanese officials told their counterparts in the UK that if “the EMA were to transfer to other EU Member States, the appeal of London as an environment for the development of pharmaceuticals would be lost, which could possibly lead to a shift in the flow of R&D funds and personnel to Continental Europe.”

Bioevents

European Life Sciences CEO Forum & Exhibition on March 6-7, Zurich (Switzerland)

BIO Asia on March 14-15, in Tokyo (Japan)

BIO-Europe Spring on March 20-22, in Barcelona (Spain)

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)

9^th Annual China BIO Partnering Forum on May 10-11 in Shunde (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)

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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