Biopharmaceutical News Week 40

Acquisitions /mergers/joint-ventures

Teva acquires Mexico-based generic company Representaciones e Investiagaciones Medicas known as Rimsa for $2.3 billion and beefs up in emerging markets. The buyout is expected to close early next year.

Business

MedImmune licenses 3M Drug Delivery Systems’ MEDI9197, a next generation “toll-like” receptor agonist as a head and neck cancer immunotherapy treatment. Under the terms of the deal MedImmune will be responsible of the development and gain exclusive rights to new molecules arising from the collaboration. Financial terms were not disclosed.

Merck Serono sells rare disease metabolic disorder phenylketonuria (PKU) Kuvan and Peg-Pal (pegvaliase) rights back to BioMarin (San Rafael, CA, USA) in a deal worth $588 million. Merck Serono acquired the rights to the two drugs back in 2005. Kuvan (sapropterin) is the first treatment approved for hyperphenylalaninemia due to PKU and has orphan drug status. Peg-Pal (pegvaliase) is an investigational drug targeting the same indication. BioMarin will pay Merck Serono €340 million up front for worldwide rights to Kuvan (excluding Japan), plus €60 million in sales-related milestone payments. The deal also includes €125 million in potential milestone payments on pegvaliase.

Sanofi Genzyme opts for Alnylam’s (Cambridge, MA, USA) ALN-AT3 hemophilia programme in territories outside of Western Europe and the US. This will be the first product from the Alnylam pipeline that Genzyme has selected since the establishment of their alliance in January 2014. ALN-AT3 is a subcutaneous RNAi investigational drug for the treatment of hemophilia which acts through the knockdown of antithrombin.

Astellas Pharma (Tokyo, Japan) collaborates with Chromocell (New Brunswick, NJ, USA) to develop and market CC8464 and back-up candidates which are indicated for the treatment of neuropathic and other pain conditions. CC8464 is an oral, peripherally acting inhibitor of NaV1.7, an ion channel which is involved in the transmission of pain. Under the terms of the agreement Astellas gains worldwide rights to the candidates and will pay an upfront fee of $15 million and more than $500 million in development and regulatory contingent fees and well as sales milestones.

Xoma (Berkeley, CA, USA) enters into a TGFb (anti–transforming growth factor-beta) antibody programme with Novartis to discover and develop drugs against the progression of advanced cancer and fibrosis. Under the terms of the agreement, XOMA will receive an upfront payment of $37 million, up to $480 million in various milestones and mid-single-digit to low double-digit royalties on net sales. TGFb is a potent immune suppressive cytokine involved in many cellular processes, including inhibition of cell growth and immune suppression.

Intrexon (Germantown, MD, USA) and ZIOPHARM Oncology (Boston, MA, USA) partner to develop new immunotherapies to treat and prevent graft-versus-host diseases based on engineered T cells aimed at delivering interleukin-2 into the immune system. Under the terms of the deal both companies will share operating costs and Intrexon will receive a $10 million technology access fee in cash plus reimbursements of all R&D costs.

GlaxoSmithKline continues to advance inhaled therapeutics through a deal with Liquidia technologies, a spinout of University of North Carolina. GSK has exercised an option, under a pre-existing collaboration, to license Liquidia PRINT technology, a platform that enables precise tailoring of particle size, shape, charge, hydrophobicity and composition, which can optimise the safety and effectiveness of vaccines or therapeutics. Financial terms of the deal were undisclosed.

Teijin Pharma and PeptiDream, two Tokyo-based companies have entered a collaboration agreement on the discovery and development of macrocyclic peptides based on PeptiDream Discovery Platform, which target areas of interest selected by Teijin. PeptiDream will receive an upfront payment, research funding and development milestones as well as royalties on sales on products arising from the collaboration.

Approval of drugs, vaccines, diagnostics and devices

European Commission approves Regeneron and Sanofi’s Praluent (alirocumab) for the treatment of hypercholesterolemia. The drug will be available in a single-dose (75 mg or 150 mg) pre-filled pen that patients can self-administer.

US FDA approves

…two diabetes drugs from Novo Nordisk. Long awaited Tresyba which contains insulin degludec and Ryzodeg which contains insulin degludec in a soluble co-formulation with insulin aspar. Tresiba is a once-daily new-generation basal insulin analogue with a half-life of 25 hours and a duration of action of at least 42 hours and is already being sold in 30 countries. Ryzodeg can be administered once or twice daily with any main meal.

… and Bristol-Myer’s Squibb combination of Yervoy (ipilimumab) and Opdivo (nivilumab) for the treatment of patients with BRAF V600 wild-type unresectable or metastatic melanoma. The approval is based on data showing a statistically significant increase in response rate in patients treated with the Opdivo/Yervoy regimen compared to those given Yervoy alone (60% versus 11%). The combination also showed a 60% reduction in the risk of progression versus Yervoy monotherapy: median progression-free survival was 8.9 months versus 4.7 months. Opdivo and Yervoy are both US-approved monoclonal antibodies and immune checkpoint inhibitors targeting separate checkpoint pathways.

Drugs at clinical stage

US FDA

…accepts for review Sanofi’s NDA for lixisenatide, a once-daily prandial GLP-1 receptor agonist for the treatment of type 2 diabetes. Lixisenatide is already marketed in Europe under the brand name Lyxumia.

…grants Fast Track status to Biotime’s (Alameda, CA, USA) OpRegen, a cell-based therapeutic consisting of retinal pigment endothelial cells for the treatment of severe forms of age-related macular degeneration.

…and grants Orphan Drug status to Regenxbio’s (Rockville, MD, USA) RGX-111, a gene therapy product, for the treatment of mucopolysaccaridosis type 1, an inherited disorder caused by the lack of an enzyme called alpha-L-iruduronidase.

In a recent meeting European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has endorsed approval of nineteen new drugs for the months to come.

Novartis reported positive phase 3 results with Afinitor (everolimus) in patients with advanced, progressive neuroendocrine GI or lung tumors. Everolimus, an mTOR inhibitor, reduced the risk of cancer progression of 52% versus placebo.

Roche reported positive phase 3 results with ocrelizumab for the treatment of primary progressive multiple sclerosis.

Science and Technology

Surgeons at Moorfields Eye Hospital in London, have carried out the first stem cell therapy designed to treat wet age-related macular degeneration. The cells were used to replace those at the back of the eye affected by the disease, through a specially engineered patch inserted behind the retina.

Skarp Technolgies (Irvine, CA, USA) have developed the world’s first laser razor which offers shaving free of irritation, razor burns and ingrown hairs. The technology is based on the discovery of the existence of a chromophore, in any color hair but not in the skin, which will be cut when hit by a particular wavelength.

Medical Devices and Diagnosis News

A new study reveals how a genetic test called Oncotype DX was successful in predicting which patients with early-stage breast cancer are unlikely to benefit from chemotherapy. The test works by searching for the presence of 21 breast cancer-related genes in breast tissue, producing a score range from 0-100, with a higher score indicating a greater risk for recurrence. The team used the test on 10,273 women ages 18-75 who had early-stage, hormone receptor-positive breast cancer. According to Dr. Sparano of Montefiore Medical Center in New York (NY, USA) his studies suggest that the Oncotype DX test may be an effective way to predict which women with hormone receptor-positive breast cancer could avoid chemotherapy without raising their risk for recurrence. The team found that around 99% of low-risk women treated with hormone therapy alone did not experience breast cancer recurrence within 5 years and the rate of invasive disease-free survival at 5 years was almost 94%, while the risk of cancer returning at a distant site was less than 1%.

Cost and Pricing

Novo Nordisk intends to launch its long-acting basal insulin Tresiba as well as the combo drug Ryzodeg (see above) at "a moderate premium" to Novo's older basal insulin Levemir and to Sanofi’s Lantus. Sanofi priced Toujeo on par with Lantus. Analysts had predicted lower pricing as a move to gain market share quickly from the older medications.

After the refusal, earlier this month, from the NHS England to reimburse Kadcyla (trastuzumab emtansine), the first and only targeted treatment for secondary breast cancer priced at an estimated cost of £90,000 per course, the UK Charity Breast Cancer Now is petitioning Roche to cut the price of the drug.

NICE (The National Institute for Health Care and Excellence) has now issued a Final Appraisal Determination rejecting Celgen’s Otezla (apremilast) because, despite recognising the drug as an innovative step forward in psoriasis treatment, it failed to fall within bounds of what is normally considered value-for-money for the NHS.

Miscellaneous

Sanofi and Eli Lilly settle their patent dispute regarding Lilly’s insulin glarginine product, Basalgar, a Lantus biosimilar, tentatively approved by the US FDA in August 2014. Under the terms of the settlement Sanofi grants Lilly a royalty-bearing license which will enable Lilly to launch Besalgar in the U.S. on December 15, 2016 with alliance partner Boehringer Ingelheim. This royalty-deal agreement represents a 6-month reprieve for Solostar (the injectable pen version of Sanofi's Lantus). Lilly intends to request final clearance from the FDA as soon as feasible. Specific financial details of the settlement were not disclosed.

GlaxoSmithKline announces the selling of its French R&D site in Les Ullis (Paris region) as part of a global restructuring move but also indicates that it will increase its manufacturing presence in the country.

Genowate Biotechnology (Taiwan) has started construction of an insulin manufacturing facility in Changzhou National Hi-tech District (China) by investing up to $1 billion and intends to compete with multinationals such as Eli Lilly, Novo Nordisk and Sanofi as well as with domestic companies. The unit will house a one metric ton fermentation production line and is forecast to be online in 2018, "Once construction is completed and the facility is put into full production, annual production is expected to reach 10 tons of insulin series products and APIs plus 1 billion bottles of preparations." the company said in the release.

Bioevents

Innovation Days on October 5-6 in Paris (France)
FierceBiotech Executive Summitt on October 12 in London (UK)
BIO Japan on October 13-16 in Yokohama (Japan)
BIO Latin America on October 14-16 in Rio de Janeiro (Brazil)
2015 Pharmaceutical/Medtech Dealmaking Symposium on October 15-16 in Chicago (USA)
BIO Investor Forum on October 20-21 in San Francisco (USA)
BIO Europe 2015 on November 2-4 in Munich (Germany)
Biofit 2015 on December 1-2 in Strasbourg (France)