Ashley Roberts

	The University of Pennsylvania (Penn) announced on June 15, 2015 that it had entered into a manufacturing collaboration with WuXi AppTec. The collaboration was developed to combine Penn’s viral vector production with the knowledge of manufacturing and infrastructure from WuXi. Penn will work with WuXi on manufacturing processes within cGMP guidelines for the production of viral vectors in WuXi’s 145,000-square-foot-facility at the Navy Yard in Philadelphia, PA.

	The Gene Therapy Program at Penn researches gene therapies to develop gene vectors derived from recombinant viruses, with a focus on developing new adeno-associated virus (AAV) vectors, as well as adenovirus and lentivirus research. According to a press release, the “current clinical focus is in the area of orphan and infectious diseases,” and collaboration with academic and biopharmaceutical partners helps with clinical translation of the research.

	“Advances in the technology of gene transfer developed at the University of Pennsylvania have ushered in an era of exciting translational research in gene therapy. A critical step toward successful commercialization of these products is the development of processes and analytics for scalable production of vectors. The opportunity for Penn to partner with WuXi AppTec, Inc in the commercial production of gene-therapy vectors will greatly accelerate their development as products and access to patients,” said James M. Wilson MD, PhD, professor and director of the Gene Therapy Program and the Orphan Disease Center at the Perelman School of Medicine, in a press release.

	Earlier in the month, REGENXBIO announced that it would partner with WuXi to manufacture AAV gene therapy treatments. The 

 mentions the Penn labratory run by Wilson helping to facilitate a successful collaboration in the development of viral vectors.

Articles

The University of Pennsylvania announces that it will collaborate with WuXi AppTech to research and develop gene vectors derived from recombinant viruses.

Penn Announces Gene Therapy Collaboration with WuXi

	Pharmacy benefit manager Prime Therapeutics released 

 outlining how proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, meant to lower low density lipoprotein (LDL), could cost the US health system up to $23.3 billion per year. Two PCSK9 inhibitors in particular-Regeneron and Sanofi’s Praluent (alirocumab), and Amgen’s Repatha (evolocumab)-are of interest because an FDA advisory committee will meet to discuss them in June 2015. FDA will review PCSK9 inhibitor Praulent first, on June 9, 2015, and Repatha will be reviewed one day later, on June 10, 2015. The FDA advisory committees will review each drug’s nonclinical background, efficacy and safety, clinical efficacy, and clinical pharmacology profiles.

	In the research released by Prime, the addition of these drugs to the marketplace could increase per member per month (PMPM) costs by $0.93 to $6.71 in commercially insured coverage costs, and up to $15.66 PMPM in Medicare coverage costs. The drugs, if approved, would primarily be used to treat familial hypercholesterolemia, but could also be approved to lower cholesterol in for a larger population of patients who are statin intolerant. Estimates of the potential drug prices are between $7000 and $12,000 per year. In a model to estimate the number of members who may use these products, Prime used an estimated cost of $10,000 per year and reviewed pharmacy and medical claims of commercially insured and Medicare Part D members in 2014 and 2015.

	Prime developed three scenarios for approval of PCSK9s and “forecasted potential use and associated costs among Prime’s commercial population at one year after launch.” The first scenario includes an increase of  $0.93 PMPM if approved to treat patients with familial hypercholesterolemia with an intolerance or resistance to traditional statins. If approved for this indication, an estimated 112 per 100,000 commercially insured patients could receive the drugs at this cost. The second scenario includes approval for the treatment of familial hypercholesterolemia with an intolerance or resistance to traditional statins and approval for secondary prevention in patients with cardiovascular disease “who are at high risk and are statin intolerant or resistant.” This scenario would affect an estimated 395 per 100,000 commercially insured members who could receive the drugs, costing them $3.29 PMPM. The third scenario would be if the drug became available to all statin intolerant or resistant people, regardless of risks involved. This would affect approximately 806 per 100,000 commercially insured members who could receive the drug at $6.71 PMPM.  Costs for Medicare Part D members with a high risk of cardiovascular disease were estimated to be much higher, ranging from 1500 per 100,000 members treated at $12.56 PMPM to 1880 per 100,000 members treated at $15.66 PMPM, due to the need for this patient group to use medicines to control cholesterol. 

	 “If not managed appropriately, the costs of PCSK9s could have a dramatic impact on overall drug spending starting later this summer. In a couple years PCSK9s could cost America the equivalent of $73 per person per year,” said Pete Clagett, senior vice-president of integrated care and specialty at Prime, in a press release.

As FDA advisory committees meet on two potential PCSK9 inhibitors, Prime Therapeutics analyzes the impact that this class of drugs may have on overall drug spending.

Will New PCSK9 Drugs Affect Overall Drug Spending?

	On June 3, 2015, the first day of CPhI Istanbul (June 3–5, 2015), UBM EMEA announced its findings of the 

Pharma Insights Turkey Market Report 2015

. The report, which is part of a longer report available from CPhI Istanbul titled 

Turkish Pharmaceuticals 2015: Turkey, Research & Development and Regional Growth

, was compiled with the help of Global Business Reports. The report is an analysis of the pharma market across Turkey, including all major Turkish manufacturers, as well as an evaluation of conditions for both foreign and domestic companies. According to the report, the pharmaceutical industry in Turkey increased by 8.8% in 2014 from the previous year, with growth in the coming years expected to come mostly from generic drugs.

	The markets most traditionally targeted by Turkey, including the Middle East and across North Africa, have slowed because of “political instability and regional conflict,” causing an increase in exports to countries not typically targeted by Turkey. Currently, the country with the highest growth in 2014 exports from Turkey is South Korea, which experienced a 260% annual increase, while Russia saw an increase of 81%. Markets such as Switzerland, Germany, Iraq, Iran, the US, and Azerbaijan currently make up Turkey’s largest export market for pharmaceuticals. The report writes that Turkey will look to push exports into new countries including investments into facilities in Commonwealth of Independent States (CIS) nations to gain more access into the Russian market, as drugs imported from CIS nations will be considered domestic in Russia. Turkey will have an advantage over Western countries hesitant to enter CIS economies because of geopolitical concerns, according to the report.

	While the Turkish market is facing problems with government reimbursement models and fixed-rate price conversion, the government has agreed to support the industry to reduce the trade deficit. Because domestic production is low, however, Turkish manufacturers surveyed for the report agreed that the Turkish government “could, and should, do more to facilitate the expansion of the domestic market. For instance, the government could increase incentives for the development of research and development-centered products.”

	The report listed biosimilars and international partnerships as two of the driving forces in the Turkish market. Companies are looking into the development of biosimilars, “particularly as an export product into the EU.” The report also listed the involvement of universities as a growing stream of support, in that the academic community may eventually enable the country to adapt and meet the changing skills needed within the industry.

CPhI Pharma Insights’ Turkey Market Report reveals, the growth and strategic plans for the future of the pharmaceutical industry in Turkey.

Turkey Expands Reach in Pharma Market

	On May 21, 2015, eight groups of physicians sent a letter to FDA Commissioner Stephen Ostroff stressing the need for product labeling on biosimilars containing all data needed for physicians to make prescribing decisions for patients. The eight groups consisted of Alliance for Patient Access, American Association of Clinical Endocrinologists, American College of Rheumatology, Biologics Prescribers Collaborative, Clinical Immunology Society, Coalition of State Rheumatology Organizations, Endocrine Society, and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.

	Unlike generics, biosimilars are not interchangeable, necessitating more information to be available for prescribers, such as indications and immunogenicity. Increased data on biosimilar labels will increase patient safety, and physician confidence in prescription. According to a press release, the letter to FDA states, “As FDA is aware, the label is a critical tool for physicians to both make prescribing decisions and manage potential adverse events, including side effects and drug-to-drug interactions. As such, it is of the utmost importance that any drug label be complete and accurate."

	The press release continues by referencing FDA’s 2012 Draft Guidance on Biosimilars, which requested that proposed products should include all data on the label that would assist physicians to make the decision to prescribe to a patient. The 2012 Draft Guidance included a statement on determining interchangeability between a biosimilar and its reference product. It may be beneficial for biosimilars to list data from the biosimilar and its reference biologic. Peter Pitts, former FDA commissioner, writes in a 

 that on the label for the recently approved Zarxio (filgrastim-sndz), there are no references to “biosimilar” or the clinical data that led the biosimilar to be approved, leaving the label to look almost identical to the reference biologic, Neupogen (filgrastim). Pitts makes a particularly good point in that the transparency in listing data on labels would help biosimilar manufacturers gain trust and consideration from physicians and patients.

Eight physician groups wrote to the commissioner of FDA to stress the importance of transparency in biosimilar labeling to decrease prescribing risks.

Physician Groups Band Together on Labeling of Biosimilars

 of prescription drugs, announced on May 21, 2015 that it entered into a definitive agreement to acquire Omnicare for $98 per share, or a total enterprise value of approximately $12.7 billion, including $2.3 billion in debt. Omnicare specializes in long-term and specialty care, which will allow CVS to move further into these areas of focus.

	"The acquisition of Omnicare significantly expands our business, providing CVS Health access into a new pharmacy dispensing channel. It also creates new opportunities for us to extend our high-quality, innovative pharmacy programs to a broader population of seniors and chronic care patients as they transition across the care continuum. We have been impressed by the Omnicare team and what they have created for the patients they serve,” said Larry Merlo, CVS Health president and CEO, in a press release.

	According to a press release from the company, the aging US population will spur a movement toward more long-term facility use in the future. This rise in elderly patrons will increase the need for health care providers in the senior sector. Rising prices of specialty drugs are causing companies to search for ways to manage drug prices to prevent pushing patients away. 

 writes that as more Americans require expensive biologics, they will also need specialty pharmacies to dispense them. In light of this trend, large pharmacies have been scooping up benefit managers to help them manage rising costs related to specialty pharmaceuticals. 

reports that pharmacy service M&A has been on the rise. In March 2015, UnitedHealth Group 

 it would buy Catamaran for $12.8 billion and, earlier in the year, Rite Aid agreed to buy EnvisionRx for $2 billion.

 that it had inked a deal with AbbVie to offer its hepatitis C treatment, Viekira Pak, exclusively to its members. The deal came after Express Scripts made it known that it believed competing hepatitis C treatments from Gilead carried prices too high for members to pay. Shortly after Express Scripts vowed loyalty to Abbvie, CVS Health announced that it would exclusively offer Gilead’s Harvoni (ledipasvir and sofosbuvir) and Sovaldi (sofosbuvir) hepatitis C treatments to members of CVS/Caremark, exchange, Medicare Part D, and Medicaid formularies.

CVS Health signed a definitive agreement to acquire Omnicare for $12.7 billion to expand its reach to assisted living and long-term care facilities.

CVS Inks Deal to Acquire Omnicare for $12.7 Billion

, FDA approved Novartis Sandoz’s biosimilar, Zarxio (filgrastim-sndz), a biologically similar drug to Amgen’s Neupogen (filgrastim). This approval marked the first of its kind within the United States. Zarxio was approved for all five indications for which Amgen’s original drug was approved. However, now Sandoz will need to take the drug off the US market until patent dispute issues are resolved with Amgen. On May 5, 2015, the US Court of Appeals granted Amgen’s request to block the biosimilar from being sold in the US, at least until June 3 when, according to the 

, oral arguments are scheduled. Amgen has appealed the lower-court ruling that allowed Zarxio to enter the US market.

	Sandoz agreed to delay sales of Zarxio in the US after it was approved due to the ongoing legal battle with Amgen. Amgen alleged that Sandoz failed to supply Amgen with manufacturing information and a biologics license application (BLA) within 20 days of FDA acceptance, something that it says is US regulatory policy. A US District Judge in San Francisco 

 Amgen’s request to block the launch of Zarxio on March 19, 2015, stating that neither the failure to provide manufacturing information or the BLA to Amgen, nor Sandoz’s plans to go to market with the drug “constitutes wrongful or unlawful behavior.” Until the end of the injunction, the 

 that Amgen is required to pay Sandoz bond to cover damages resulting from the biosimilar being taken off the market. 

The US Court of Appeals granted Amgen’s request to block Novartis’ Neupogen biosimilar, Zarxio, from the US market until the court resolves litigation between the two companies.