Randi Hernandez was science editor at Pharmaceutical Technology from September 2014 to May 2017.

Randi Hernandez

	The National Institutes of Health (NIH) announced on Oct. 5, 2015 that it will fund four science-based programs that will “provide catalytic support to areas of research that no one institute or center at NIH would be able to address on its own,” according to a statement from James M. Anderson, MD, PhD, director of the Division of Program Coordination, Planning, and Strategic Initiatives. The monies will come from the NIH Common Fund and total more than $54 million.

	While the funds will be allotted to four programs focusing on a range of diverse biomedical topics (behavior change, nuclear organization, and a genetic sequencing database for pediatric cancer patients), the program that seems especially relevant to the bioprocessing community is the Glycoscience Program, which will address the study of proteins and lipids that have glycoproteins attached to them. The NIH will contribute $10 million to 23 research teams so that they can find solutions to easily analyze, synthesize, and characterize glycans. The variation in glycosylation profiles of therapeutic glycoproteins remains a major challenge to the industry, and the available technologies used to characterize glycoforms vary in accuracy, according to 

 by Jennifer Fournier of Waters Corporation. Concerns also exist with the analysis of glycans at various testing facilities, she says, as tests in different locations using disparate methods can produce variable results.

 to academic universities, with the exception of Batelle Pacific Northwest Laboratories, which received a grant to study “A hybrid IMS-MS platform for ultrasensitive and high-resolution glycan analysis,” and Beth Israel Deaconess Medical Center, which was awarded a grant to study the synthesis of glycosulfopeptides and related bioconjugates.

Articles

Through the Glycoscience Program, the National Institute of Health will contribute $10 million to advance the study of carbohydrates and the compounds that interact with them.

NIH Dedicates Funds to Carbohydrate Science

 comparing the efficacy of an immunotherapy with chemotherapy as a second-line treatment for nonsquamous non–small-cell lung cancer (NSCLC) signal a potential turning point in the therapeutic landscape of cancer. The study showed that the PD-1 immune checkpoint inhibitor-antibody nivolumab improved overall survival rate better than a chemotherapy regimen of docetaxel (51% vs. 39%, respectively). Docetaxel is one of the most commonly used second-line treatments for advanced NSCLC, according to a press release from the UT Southwestern Medical Center, which was involved in the study.

	Although the overall rate of survival was better with nivolumab, progression-free survival was actually better with docetaxel (median, 2.3 months and 4.2 months, respectively). The rate of progression-free survival after one year, however, was higher with the nivolumab group than with the chemo group (19% and 8%, respectively). The researchers attributed the cause of the lower progression-free survival in the nivolumab group to typical delays in benefit that are associated with treatment with immunomodulators. "This clinical trial shows that people with lung cancer not only live longer when treated with the immunotherapy drug nivolumab, but their quality of life is better and toxicities are fewer and less severe," said David Gerber, MD, associate professor of internal medicine at UT Southwestern- a contributing author to the study-in a university 

	Tumor-expressed ligands PD-L1 and PD-L2 down-regulate activation of T cells to evade attack by the immune system. The researchers concluded that patients whose tumors expressed higher levels of PD-L1 responded better to treatment with nivolumab; 24% of patients continued nivolumab treatment beyond the 12-week study period, and of these 71 patients, 16 (23%) had a “nonconventional pattern of benefit,” according to study researchers. Although the adverse events were generally similar in both groups, a small group of patients in the nivolumab group experienced autoimmune toxicities affecting various organs.

	Sources: NEJM, UT Southwestern Medical Center
	 

The results from an international study on nivolumumab, published in the New England Journal of Medicine, suggest a paradigm shift in the standard of care for previously treated lung cancer patients.

New Study Reveals Immunotherapy More Effective Than Chemotherapy

	Roche announced positive Phase III results for its drug ocrelizumab on Sept. 28, 2015, saying that, compared with placebo, the investigational drug reduced the progression of clinical disability in primary-progressive multiple sclerosis (PPMS) over the course of 12 weeks. Clinical disability was measured by the Expanded Disability Status Scale (EDSS).

	Ocrelizumab is touted as the “first investigational medicine to slow a clinically meaningful and statistically significant effect on the progression of disease in primary-progressive MS,” according to by Roche’s Chief Medical Officer and Head of Global Product Development Sandra Horning, MD, who made this statement in a press release. Moreover, Roche says the clinical trial data substantiate the claims that B cells are influential in MS pathogenesis, giving B-cell-directed therapeutic approaches validity. Many existing therapies, such as glatiramer acetate, decrease inflammation through mechanisms related to regulatory T cells, rather than B cells.

	So far, no specific treatments have been shown to be effective for PPMS, which according to the 

, is more difficult to diagnose and treat than relapsing forms of the disease. The current medications approved by FDA for the treatment of PPMS do not attack the underlying mechanisms of the disease; instead, the approved disease-modifying therapies tackle the symptoms of the disease and work primarily by reducing inflammation in the central nervous system (CNS).

	Top-line data from the ORATORIO trial will be presented at the 31

 congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS), and Roche plans to submit these data to global regulatory authorities by early 2016.

Roche says its trial results validate the hypothesis that B lymphocytes are key targets in the mediation of the inflammatory damage characteristic of multiple sclerosis.

Roche's Ocrelizumab Reduces MS Progression in Phase III Trials

	Drug price hikes-like that of the one seen in the highly publicized case of Turing Pharmaceuticals' Daraprim-are prompting public outcry and are demonizing the industry for those who see people like Martin Shkreli as representative of all pharmaceutical executives. But capping drug price increases may affect actual patient costs less than imagined, and may have a bigger impact on pharmacy benefit managers and insurance companies.

	Although Hillary Clinton refers to capping “drug prices”, the monthly out-of-pocket cap she proposes in her new plan is actually a cap on patient co-pays, not drug prices. If drug prices go up, and a monthly co-pay cap were in place, where would insurance companies make up the lost revenue? A cap on co-pays could theoretically drive insurance premiums up and total healthcare expenditures for patients may not actually change, they would just simply shift. "The problem with potentially implementing a cap on co-pays (in addition to the one that already exists through the out-of-pocket max) is that the patient is only paying a small fraction of the total cost of these medications," David Whitrap, senior director of corporate communications at Express Scripts, told 

. "It's the employers and taxpayers who are funding the lion's share of prescription drug costs in the United States, and the co-pay cap does nothing to curb rising drug prices."

	Discounts from drug manufacturers to insurance companies or pharmacy benefit managers (PBMs) are rarely passed on to the consumer in the form of lower co-pays, notes Peter J. Pitts, who is president of the Center for Medicine in the Public Interest, chief regulatory officer at Adherent Health Strategies, and a former FDA associate commissioner. However, when drug prices increase, a patient may be expected to make up the cost difference, especially if a drug is moved to a 

 within an insurance plan. When expensive medications, such as biologics, are moved to a higher tier, more of the cost-sharing burden ends up on the patients. If a PBM decides a drug is too expensive, and says it will not cover a drug at all (as in the recent case of Express Scripts with Sovaldi), a patient may have to pay full price for the drug if they want the drug as prescribed by his or her physician. In this example, the co-pay cap suggested by Clinton would not put a dent in what a consumer actually pays for a drug, as the cap would only apply to the drugs that are “covered”, or included in a PBM or insurer formulary list.

	Out-of-pocket (OOP) caps, however, have the potential to reduce the effectiveness of drug benefits with higher OOP costs-particularly co-insurance, says Richard Evans, an analyst at Sovereign & Sector and a former Roche executive. “Without OOP caps, under co-insurance patients care a lot about absolute prices, and the rate at which prices grow-since this affects their OOP cost,” Evans says. “Under fixed co-payments, absolute drug prices and rate of price growth don’t have an immediate effect on patients. If you install OOP caps, then you ultimately force co-insurance to behave a lot like fixed co-pays, since OOP caps limit the extent to which OOP costs can rise under co-insurance.” Co-insurance models are typically more expensive for patients than co-pay models-even after a patient has met his or her deductible-so a patient may reach his or her OOP cap more quickly under co-insurance. “Ironically, this would give manufacturers more pricing power, not less,” Evans added.

	Insurers and PBMs may, therefore, be particularly interested in how policy surrounding the proposed pricing caps develops. PBM Express Scripts 

 it already closely tracks manufacturer price increases and will continue to work to ensure that its “clients are not paying more for prescription drugs that provide no additional health benefit."

Although the presidential candidate seeks to cap monthly drug costs to $250 for covered drugs, what will happen to drug costs that are associated with co-insurance?

How Clinton's Drug Plan Could Give Manufacturers Even More Pricing Power

	Innate Pharma announced on Sept. 17, 2015 that it expects data on its first-in-class investigational monoclonal antibody (mAb) lirilumab-now in Phase I clinical trials-by 2016.

	According to Innate's website, lirilumab works by blocking interaction between killer-cell immunoglobulin-like receptors (KIR) on natural killer (NK) cells with their ligands. Blocking the binding of KIR on NK cells facilitates a boost in immune response characterized by enhanced activation of NK cells and is thought to improve the tumor cell destruction capabilities of these cells.

	Lirilumab and all related compounds blocking KIR receptors are licensed to Bristol-Myers Squibb through an agreement from July 2011. The efficacy of the monoclonal antibody (mAb) is being tested in a total of 

-as a monotherapy in one trial and in combination with other products in the remaining six trials. The therapy is being investigated as a treatment option for select solid tumors, select hematological tumors, multiple myeloma, acute myeloid leukemia, and chronic lymphocytic leukemia.

	Innate is also developing another immune-oncology target-IPH2201-

. This deal, which was announced in April 2015, allows Innate to co-develop, co-promote, and co-commercialize IPH2201, a strategy which Innate's CEO Hervé Brailly said in a 

 will allow Innate to further mature the company's "capabilities in late-stage development". Additional Phase II clinical trials for IPH2201 will be opened in the second half of 2015, 

	IPH2201 is a first-in-class humanized mAb targeting NKG2A receptors expressed on tumor infiltrating cytotoxic NK and CD8 T lymphocytes. By expressing HLA-E, Cancer cells can protect themselves from killing by NKG2A+ immune cells by expressing HLA-E on their surfaces. The overexpression of HLA-E in several cancer types is thought to protect abnormal cancer cells from attack by the immune system, allowing the cancer cells to evade destruction via a "cloaking" mechanism. IPH2201 works by blocking the binding of NKG2A receptors on immune cells to HLA-E, freeing up the NKG2A receptors, thereby allowing activation of NK and cytotoxic T-cell responses.

 IPH2201 is the “only checkpoint inhibitor developed to date that is capable of acting simultaneously on T and NK cells, which could provide a more effective immune response.”

The fully humanized monoclonal antibody is licensed to Bristol-Myers Squibb.

Innate Pharma Expects Data on Lirilumab by 2016

	In preparation for a burgeoning biologics pipeline, AstraZeneca announced on Sept. 11, 2015 that it will purchase Amgen’s Boulder, CO manufacturing facility. According to Pam Cheng, executive vice-president, operations and information technology at AstraZeneca, the “facility will support the progression of biotech drug candidates” and will give AstraZeneca and its biologics research arm MedImmune “the flexibility and capacity” to meet the needs of its expanding biologics portfolio.

	The Colorado plant is the latest development in AstraZeneca’s long-term plan to secure manufacturing capacity among various different locations. Biologics currently make up half of AstraZeneca’s current pipeline, according to the company, and many of its recent expansion efforts have been focused on supporting this pipeline. In May 2015, AstraZeneca expanded its overall biologics capacity through the $285-million purchase of a facility in Södertälje, Sweden. Prior to that, in November 2014, the company 

 to invest approximately $200 million in its Frederick, MD plant for the production of investigational biologic medications, with a special focus on that plant’s cell culture operations.

	The drugs that may be manufactured within the new plants could include brodalumab, AstraZeneca and Valeant’s investigational product for the treatment of psoriasis, and many of AstraZeneca’s investigational immune-oncology agents that it has in development, such as durvalumab (MEDI4736), an anti-PD-L1 monoclonal antibody for the treatment of patients with non-small cell lung cancer. AstraZeneca is partnering with Inovio Pharmaceuticals-a biotechnology company developing DNA-based immunotherapies-for the treatment of human papillomavirus (HPV) types 16 and 18. It also has a partnership with Kyowa Hakko Kirin to commercialize benralizumab for asthma and chronic obstructive pulmonary disease.

According to AstraZeneca, the purchase of the biologics bulk plant will double the company's biologics manufacturing capacity in the US.