Biopharmaceutical News Week 42

Acquisitions /mergers/joint-ventures

Roche acquires Adheron Therapeutics (San Francisco, CA, USA) for up to $580 million. Adheron has developed a technology which disrupts immune cell adhesion through a protein called Cadherin-11 with a current lead SDP051 which has completed Phase 1 studies. Under the terms of the agreement Roche will pay an upfront of $105 million and milestone fees of up to $475 million.

Business

Bristol-Myers Squibb and Five Prime Therapeutics (San Francisco, CA, USA) have entered into a $1.74 billion worldwide license and collaboration agreement to commercialise FPA008, a colony stimulating factor 1 receptor drug. Under the terms of the deal Five Prime will conduct the ongoing clinical trial evaluating the combination of BMS' Opdivo (nivolumab) and FPA008 in six different tumour settings and B-MS will make an upfront payment of $350 million and take on the development and manufacture of FPA008. In addition to the upfront payment, Five Prime will receive up to $1.05 billion in development and regulatory milestone payments for oncology indications and up to $340 million for non-oncology indications, as well as double digit royalties.

Pfizer acquires the commercialization rights of Elelyso (taliglucerase alfa) for the treatment of type 1 Gaucher’s disease from Protalix Bio Therapeutics (Carmiel, Israel) for a deal valued at $46 million.

Novartis increases its stake in Gamida Cell (Jerusalem, Israel) in acquiring an additional 2.5% of the share for $15 million. The investment will support the development of NiCord, an ex vivo expanded cell graft from umbilical cord blood, which is in development as an alternative to bone marrow transplant for patients who cannot find a fully matched donor. In June Novartis said it had decided not to acquire the company despite the fact that all predetermined milestones had been met and that it would “explore suitable alternatives” to stay close to Gamida.

OBI Pharma (Taiwan) has signed an agreement with Merck & Co regarding the transfer of exclusive rights to develop and commercialize Dificid, an antibiotic drug, in Taiwan. Under the terms of the agreement OBI Pharma will receive an upfront payment of $3 million, milestone payments and royalties on sales.

Eli Lilly and Innovent Biologics (Shanghai-Pudong, China) have agreed to deepen their ongoing collaboration by including immune-oncology anti PD-1 bispecific antibodies and specifying the commercialisation rights of three cancer drugs arising from the collaboration. Under the terms of the new deal, Innovent will commercialise the drugs in China, while marketing of the drugs outside of China will be performed by Eli Lilly. Innovent is entitled to receive milestone fees of more than $1 billion.

AstraZeneca expands its current immunotherapy collaboration with Peregrine Pharmaceuticals (Tusting, CA, USA) and will test a combination of AstraZeneca’s anti-PD-L1 immune checkpoint inhibitor durvalumab (MEDI4736) and Peregrine’s phosphatidylserine-targeted immune-activator bavituximab, in patients with previously treated squamous or non-squamous non-small cell lung cancer. Durvalumab and bavituximab are both still investigational immunotherapy drugs. This new study builds on the non-exclusive collaboration both companies concluded in August evaluating the durvalumab/bavituximab combination with chemotherapy in multiple solid tumours.

Boehringer Ingelheim partners with Philogen (Siena, Italy), a Swiss Italian biotechnology company to discover novel immunotherapy concepts for the treatment of acute myeloid leukemia. Terms of the deal were not disclosed.

Asterias Biotherapeutics (Menlo Park, CA, USA) enters a collaboration with Cell Therapeutic Catapult (London, UK) to speed up manufacturing processes for AST-VAC2, an allogeneic cancer vaccine designed to stimulate patient immune responses to telomerase. Under the terms of the agreement, Cell Therapy Catapult will scale up manufacturing processes for the vaccine and supply batches for clinical trials and commercialisation of the product.

Takeda and University College of London are entering a new three-year collaboration to identify and validate new target genes for the treatment of neurodegenerative disorders such as Hutington’s diseases and Parkinson’s disease.

Approval of drugs, vaccines, diagnostics and devices

US FDA approves

Opdivo from Bristol-Myers Squibb for an expanded lung cancer treatment. Earlier this month, Keytruda from Merck got an NSCLL indication which is limited to second-line patients testing positive for PD-L1, whereas current Opdivo's indication is free of PD-L1 limits. This FDA approval means a larger patient populations and potential larger sales for Opdivo and should place BMS as number one in the fast growing immunotherapy field.

Praxbind (idarucizumab) from Boehringer Ingelheim for use as an emergency reversing agent (antidote) in patients treated with the anticoagulant Pradaxa (dabigatran).

…and rejects

AstraZeneca’s fixed-dose combination drug (saxagliptin and dapagliflozin) for the treatment of diabetes stating that more clinical data is required which may trigger potential years-long delay.

Pfizer supplemental New Drug Application for Xeljanz (tofacitinib citrate) a Janus Kinase (JAK) inhibitor for the treatment of moderate-to severe plaque psoriasis although the drug is already approved in the US since 2012 for the treatment of rheumatoid arthritis. The details of the complete response letter have not been disclosed, but Pfizer said it would now work with the Agency to determine an appropriate path forward to address its comments, “including providing additional safety analyses of Xeljanz for the proposed indication”.

Drugs at clinical stage

US FDA:

grants breakthrough status to RBX2660 from Rebiotix (Roseville, MN, USA) for its microbiota restoration therapy as a treatment for the treatment of patients with recurrent Clostridium difficile.
grants fast-track status to Shire’s Cinryze, a C1 esterase inhibitor, for the treatment of antibody mediated rejection in kidney transplanted patient and to Portola Pharmaceutical’s betrixaban, an anticoagulant as a long term preventive treatment against venous thromboembolism.
confirms the new drug application submission by Luye Pharma (China) for LY03004 (risperidone), an extended release injection for the treatment of schizophrenia and various psychotic disorders.

Ark Biosciences (China) a biotech developing proprietary therapeutics for respiratory viral diseases and viral hepatitis, has successfully completed a phase I clinical trial of its anti-respiratory syncytial virus (RSV) drug AK0529.

AstraZeneca temporarily pauses the development of two cancer trials assessing the safety and efficacy of the combination of AZD9291, an irreversible EGFR tyrosine kinase inhibitor, and durvalumab, an anti PD-L1 immunotherapy drug following an increase in incidents of interstitial lung disease.

Eli Lilly stops the development of evacetrapib, a CETP inhibitor, for high-risk atherosclerotic cardiovascular disease, due to insufficient efficacy and a recommendation from an independent data monitoring committee indicating that "there was a low probability the study would achieve its primary endpoint" of delaying serious cardiac events. Over recent years CETP inhibitors from Pfizer and Roche had shown efficacy but ran into safety issues in late stage clinical trials and were never registered. Evacetrapib, did not have the same safety concerns but was stopped because of lack of efficacy.

Medical Devices and Diagnosis News

In our previous news week we had indicated that US FDA had approved Boston Scientific‘s Synergy as its first third-generation bioabsorbable stent and that Abbott Xience was supposed to be the first real bioresorbable drug-eluting stent to be approved. Abbott has conducted several trials, all of which have found noninferiority to the standard of care and has published them in the New England Journal of Medicine. The same journal also published a critical editorial that pointed that the Xience results are in fact worse than standard of care. "Although the trial was designed in consultation with regulatory authorities, the absolute risk difference between the devices that is considered to be clinically unimportant–the noninferiority margin–is large at 4.5% points against a background rate of the primary outcome of 6.0% with the metallic stent. Most clinicians in everyday practice would not accept this degree of difference between two stents in their catheterization laboratories. This means that the clinical relevance of the finding of statistical noninferiority is open to question," the editorial says.

3M collaborates with Imple Neuropharma (Seattle, WA, USA) to develop its Precision Olfactory Delivery (POD) for delivery of neurological drugs into the brain. Impel says its POD device is using a nose-to-brain pathway that lacks a significant membrane barrier. Apparently, the device can deliver more than 50% of a drug in the nose's olfactory region, compared to less than 5% from standard droppers, nasal sprays or pumps. "We've successfully shown that the POD technology is highly effective in the clinic in our ongoing development programs and across diverse therapeutic areas including Alzheimer's disease, migraine, and pain management” said Imple CEO Michael Hite

Cost, Pricing and Market Access

The National Institute for Health and Care Excellence (NICE) has launched a new service that seeks to accelerate the adoption of innovative health technologies. The Office for Market Access “will speed up the adoption of innovative and cost-effective health technologies by helping companies to get the right evidence, develop a better business case and engage with the right people,” said the Institute’s health technology evaluation centre director, Carole Longson.

Valeant again under drug-pricing controversy after it revealed earlier this week that it has received two subpoena, one from the US Attorney’s Office for the District of Massachusetts and one from US Attorney’s Office for the Southern District of New York requesting materials related to the company’s pricing decisions, as well as its patient assistance and financial support programs. Valeant is in the spotlight since it became known that it had increased the price of 56 of its drugs this year by an average of 65.6%. In late September, 18 Democratic members sent a letter requesting Jason Chaffez, Chairman of the Oversight and Government Reform Committee, to send Valeant a subpoena over the Isuprel and Nitropress price increases, which increased by 525% and 212%, respectively.

US District Judge Rudolph Contreras in Washington D.C. decided earlier this week that drugmakers do not have to sell orphan drugs to rural and cancer hospitals at a discount under the federal program known as 340B. The 340B program, under the Affordable Care Act (Obamacare), requires drug companies participating in Medicaid to discount outpatient medications for hospitals and clinics to help low-income patients. Hospital groups say the decision could not only lead to higher prices for patients but also limit access to some medications and harm struggling rural hospitals which strongly rely on the 340B money to provide uncompensated care.

Miscellaneous

Results from a Phase 4 study showed that Amgen’s Prolia (denosumab) achieved greater gains in bone mineral density than the intravenous bisphosphonate zoledronic acid. The 12-month study enrolled 643 postmenopausal women with osteoporosis who had been taking oral biphosphonates for at least two years. The data were presented at the American Society for Bone and Mineral Research Annual Meeting in Seattle.

Sanofi Pasteur announces the establishment of the Global Health Vaccine Center of Innovation (GHVCI) to be headquartered at the Infectious Disease Research Institute (IDRI) in Seattle. The project, aimed at accelerating timeline and decrease development costs of life-saving vaccines, is also funded in part by a grant from the Bill & Melinda Gates Foundation.

Merck KGaA rebrands its logo "to be perceived as a vibrant technology company in the market," said Walter Huber, head of group communications. Merck Serono and Merck Millipore, will be integrated into the company, except in the US and Canada, where the American Merck & Co. owns rights to the Merck name.

Bioevents

BIO Investor Forum on October 20-21 in San Francisco (USA)
Pharma Licensing Negotiation Course on October 20-21 in Brussels (Belgium)
Pharma-Biotech Product and Company Valuation Course on October 22 in Brussels (Belgium)
BIO Europe 2015 on November 2-4 in Munich (Germany)
BIOPharma India Convention 2015 on November 3-4 in Mumbai (India)
Biofit 2015 on December 1-2 in Strasbourg (France)