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

Mergers, Acquisitions and Joint Ventures

Allergan acquires Zeltiq Aesthetics for $2.475 billion and increases its aesthetics portfolio with the US FDA approved flagship CoolScuplting System, based on its proprietary-cooling technology platform. The system works by gently cooling targeted fat cells in the body to induce a natural, controlled elimination of fat cells without affecting surrounding tissue, a  growing market with a global value of more than $4 billion.

Business

Janssen Pharmaceutical has granted Akebia Therapeutics exclusive license rights to its portfolio of hypoxia-inducible factor (HIF) prolyl hydroxylase-targeted compounds including AKB-5169 (formerly JNJ5169), a preclinical non absorbed oral HIF stabilizer being developed as a treatment for inflammatory bowel disease (IBD), Under the terms of the deal Akebia will make a $1 million upfront payment, $16.5 million in various milestones and up to $215 million in royalties.

Ipsen acquires five consumer healthcare products from Sanofi in a deal worth $83 million including Prontalgine®, an analgesic agent with a strong growth potential. The deal comes as a mandatory divestment required by the European Commission in order to achieve the completion of the deal with Boehringer Ingelheim.

ApolloBio acquires exclusive Chinese rights to develop Inovio Pharmaceuticals’ VGX63100, a late-stage vaccine candidate designed to activate functional, antigen-specific CD8 T cells to clear persistent HPV 16/18 infection and to reverse the development of precancerous cervical dysplasia related to human papillomavirus. Under the terms of the deal ApolloBio will make a $3 million upfront payment, up to $12 million near-term payments, when Chinese FDA lifts the existing VGX-3100 Phase 3 preinitiation clinical hold, which has been in place since October 2016, and up to $20 million in regulatory milestones plus double-digit royalties on future sales. ApolloBio has separately agreed to invest up to $35 million in Inovio, after the Chinese clinical hold has been lifted.

Gilead Sciences has granted Amygdala NeuroSciences rights to GS-6637, an aldehyde dehydrogenase 2 family mitochondrial (ALDH-2) inhibitor, as a treatment for alcohol and cocaine dependence. Details of the deal were disclosed.

Ionis Pharmaceuticals and wholly owned subsidiary Akcea Therapeutics have terminated their ongoing collaboration with Novartis to develop antisense drugs to treat lipid disorders. The deal had been valued at $1.7 billion.

Approval of drugs and vaccines

The European Commiission has approved Eli-Lilly’s Olumiant or baricitinib, as the first Janus Kinase (JAK) inhibitor to treat moderate-to-severe active rheumatoid arthritis who have responded inadequately to, or who are intolerant to, one or more disease-modifying antirheumatic drugs (DMARDs). The approval triggers a $65-million milestone to Incyte, under their 2009 exclusive worldwide license and collaboration agreement to develop and commercialise baricitinib.

US FDA approves:

Valeant Pharmaceuticals’ Siliq, or bradalumab, an injectable biologic as a treatment for moderate to severe plaque psoriasis in patients who are eligible for phototherapy. The approval nevertheless comes with a black box safety warn­ing on sui­ci­dal ideation and a risk mit­i­ga­tion mar­ket­ing pro­gram. The drug had initially been developed by AstraZeneca and Amgen. This US approval triggers a $130M milestone payment to licensor AstraZeneca and both companies will share the profits in the US market. Kyowa Hakko Kirin Co. owns the rights in Japan and certain other Asian countries under an agreement with Amgen. LEO Pharma owns the European rights under an agreement with AstraZeneca.

…..and Boehringer Ingelheim’s Spiriva Respimat or tiotropium bromide, a steroid free long-term, once-a-day treatment for asthma in children at least 6 years old

The European Medicines Agency (EMA) drug safety panel recommended that Actelions’ Uptravi may continue to be used in line with its current intermediate stage pulmonary arterial hypertension prescription amid a probe of five death in France.

Drugs at clinical stage

US FDA grants fast-track status to Axsome Therapeutics’ AXS-05, as a treatment-resistant depression.  AXS-05, a novel, oral combination of bupropion and dextromethorphan, is also currently evaluated as a treatment for agitation associated with Alzheimer's disease.

ViiV Healthcare, which is majority-owned by GlaxoSmithKline, with Pfizer and Shionogi, has unveiled late-stage data with SWORD showing that an experimental two-drug regimen of its dolutegravir and Janssen Science's rilpivirine was comparable in efficacy to three-or four-drug antiretroviral regimens in virologically suppressed patients.  John C Pottage, chief scientific and medical officer of ViiV Healthcare, said the results "may change our understanding of how HIV can be managed". "For more than 20 years we thought that three or more drugs were required to maintain virologic suppression, but the SWORD studies provide compelling data that suppression may be maintained with a two drug regimen of dolutegravir and rilpivirine. These data mark an exciting first step towards making two drug regimens a reality in HIV treatment," he noted.

Pfizer’s Xeljanz or tofacitinib, a Janus kinase (JAK) inhibitor, combined with methotrexate (MTX) showed to be non-inferior to Humira plus MTX a in phase 3/4 clinical trial. But Xeljanz, as monotherapy, failed to demonstrate non-inferiority versus both combination therapies. The study was the first to compare a JAK inhibitor, with and without MTX, to Humira.

Merck stops EPOCH, a phase 3 trial, with verubecestat, an investigational small molecule inhibitor of the beta-site amyloid precursor protein cleaving enzyme 1 (BACE1), as a treatment of mild-to-moderate Alzheimer’s disease, after the external data monitoring committee concluded that the drug had “virtually no chance of finding a positive clinical effect". No sig­nif­i­cant new drug for Alzheimer’s disease has been ap­proved in the past 14 years, de­spite mas­sively ex­pen­sive tri­als which all failed.

Medical Devices and Diagnosis News.

Integra LifeSciences has made a binding offer to acquire Johnson & Johnson’s Codman Neurosurgery for about $1.05 billion in cash.  Integra’s neurosurgery portfolio includes flow-regulating valves to control the flow of cerebrospinal fluid and a dural sealant system as well as devices for tissue ablation, dural repair and cranial stabilization.

US FDA approves Medtronic’s OsteoCool RF Ablation System as a palliative treatment for metastatic bone tumors. “Patients with metastatic bone cancer may be treated with conventional therapies such as opioids, chemotherapy or radiation therapy for pain palliation," the Vascular Institute of Virginia’s Sandeep Bagla said in a statement. "With the expanded indication for the OsteoCool System, I now have the option to ablate these patients' painful bone tumors when conventional therapies are considered ineffective, too slow-acting or cause unacceptable side effects."

Two research groups, (one led by C. Soto at the University of Texas Health Science Center at Houston, the other led by D. Bougard, from the Institut Français du Sang in Montpellier, France) have developed a sensitive blood test which accurately detects prions in the Creutfeld-Jacob disease, an fatal neurodegenerative disorder. Prions are scarce in the bloodstream and difficult to measure. Both teams developed methods to amplify the prions in blood samples using a technique called protein misfolding cyclic amplification (PMCA). PMCA relies on the characteristic nature of prions to cause certain healthy proteins to clump abnormally and convert into prions.

Cost, Pricing and Market Access

The UK National Institute for Health and Care Excellence (NICE) supports the use of HearthFlow FFRct Analysis to assess patients with stable recent onset chest pain. HeartFlow FFRct is a software for extracting more information from cardiac CT scans. Users send CT scan data to a HeartFlow processing center, where analysts turn the information into 3D models of coronary arteries. Details of coronary flow are featured in the models created by HeartFlow. This process, which costs the U.K. $875 per test, takes 48 hours. “The HeartFlow FFRct Analysis provides a definitive understanding of both the anatomical and functional findings, without any additional testing or risk for patients,” Liverpool Heart and Chest Hospital’s Dr. Joseph Mills said in a statement. “Application of the Heartflow FFRct Analysis is likely to transform the quality of care we can provide for patients, ensuring the most accurate diagnosis and the best treatment plan, as well reducing the need for invasive coronary angiography—a procedure not without its risks.”

…and rejects Alexion’s Kanuma, or sebelipase alpha, to treat children and adults with the rare inherited genetic disorder lysosomal acid lipase deficiency (LAL-D). Defending the decision, Professor Carole Longson, NICE health technology evaluation centre director, said: "Throughout this extremely complicated evaluation we have given the company many opportunities to improve the terms under which sebelipase alfa could be offered to patients. However, even their best offer to date falls far short given the considerably uncertainties about its longer term benefits and its very high cost." At £491,992 ($704,630), the therapy does not represent good value for all patients, NICE said in draft guidance.

A few days after receiving US FDA approval for Emflaza, as a treatment for the rare disease Duchenne muscular disorder, Marathon Pharmaceuticals runs into severe critics for an $89,000 price tag on the decades-old corticosteroid drug. US critics came from Senator Bernie Sanders, I-Vt., and Representative Elijah Cummings, D-Md. Who pointed out in their letter to Marathon’s CEO Jeffrey Aronin, that Deflazacort has been available in Canada and the European Union “for many years,” where it’s priced at about $1,000 per year. As the lawmakers point out, Marathon did not develop the drug. Instead, it acquired rights to trial data from the 1990s and “completed some additional analyses to gain approval … to sell the drug in the United States.” Marathon is now “pausing” the Emflaza commercial rollout. Another congressman watchdog, Sen. Chuck Grassley says he aims to find out if drugmakers misused a decades-old law designed to spur research into rare, neglected diseases. The frequent pharma critic says he is investigating whether “unanticipated uses” of the Orphan Drug Act have helped boost U.S. drug prices.

In a series of Tweets and Facebook posts, the global charity Médecins Sans Frontières (MSF) and its employees called on Pfizer ad GlaxoSmithKline to lower the price of their pneumonia vaccine concessions pricing to $5 for all three doses in developing countries so children may have lifesaving access where they currently do not.

Miscellaneous

According to the Agence Nationale de Sécurité du Médicament et des Produits de Santé, (ANSM), the French Health Agency, five patients recently treated for their breast cancer with a generic version of Taxotere, died in France

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)

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

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

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)

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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