Allison Gilchrist, Associate Editor

A recent analysis from Johns Hopkins University Bloomberg School of Public Health researchers found that generic forms of the biologic drug infliximab (remicade) appear to be just as safe and effective as the brand name version. The researchers analyzed 19 studies conducted through April 2016 and determined that, although the sample size was small, biosimilar drugs had safety and effectiveness profiles that were very similar to their branded counterparts. “Preliminary evidence supports the biosimilarity and interchangeability of biosimilar and reference TNF-α inhibitors,” they concluded in their study.

Infliximab is a biologic drug indicated to treat rheumatoid arthritis, inflammatory bowel disease, and psoriasis. It is in a class of drugs known as tumor necrosis factor-alpha (TNF-α) inhibitors, which suppress the body’s inflammatory response. Infliximab is one of several TNF-α inhibitor biologics that have received approval in recent years for autoimmune diseases—a lineup that includes adalimumab (Humira) and etanercept (Enbrel).

The Biologics Price Competition and Innovation Act (BPCIA) was passed in 2009, enabling biosimilars to compete with branded biologics. This law was considered to have potential to enhance patient access to advanced therapies through lower drug costs resulting from greater competition among drug manufacturers. In many ways, it was, and still is, viewed as the Hatch-Waxman Act for biologics.

Despite the BPCIA, the FDA has approved just 2 biosimilars: Zarxio, a biosimilar of filgrastim (Neupogen), and Inflectra, a biosimilar of infliximab (Remicade). Because biologic drugs are large, complex molecules manufactured from living organisms, such as bacteria and yeast, opponents of generic biologics argue that it is impossible to replicate copies that are completely identical. This, they say, could mean that certain patients could have variances in clinical response or even adverse reactions to the subtle differences of biosimilars.

“The billion-dollar question has been whether these ‘generic biologics’ are the same as the brand name versions,” says study leader G. Caleb Alexander, MD, an associate professor in the Department of Epidemiology at the Bloomberg School and co-director of the Johns Hopkins Center for Drug Safety and Effectiveness, in a press release. “The same debate occurred with the advent of less complicated generic drugs, and now it’s being hashed out all over again with much more at stake—more room for error and more potential for cost savings to the health system. But based on the available evidence, we conclude that the products we studied appear comparable, and they will definitely be cheaper.”

Biologics are used to treat cancer, HIV/AIDS, Alzheimer’s disease, and other life-threatening diseases. Developing lower-cost versions of these crucial drugs has the potential to assist a wide swath of the US population who might otherwise be unable to afford their medications. In fact, a recent analysis from the IMS Institute for Healthcare Informatics found that biosimilars have the potential to save the global health system $110 billion by 2020.

To receive FDA approval, manufacturers must show that the biosimilar is “highly similar” to the reference product, omitting minor differences in clinically inactive components. They must also demonstrate that, compared with the reference biologic, there are no clinically meaningful differences in terms of safety, purity, and potency.

In addition to approval, a biosimilar may receive an added interchangeability designation from the FDA, allowing it to be substituted for the reference biologic at the point of dispensing without the prescriber’s involvement. Because of this, biosimilars with this designation are ideal candidates for pharmacist substitution akin to generics, the authors explained.

When approaching such interchangeable biosimilar substitution, pharmacists should consider the following questions, which the researchers based on the current process for generic substitution:

		Does state law give pharmacists the authority to autonomously substitute interchangeable biosimilars or will the prescriber need to be contacted?

		What criteria define which products may be substituted?

		Is the biosimilar considered interchangeable with the prescribed product for all indications? If not, what indications can be substituted?

		Does the state require prescriber and/or patient notification or counseling?

		Does the state require recordkeeping of drugs dispensed and any related notifications of dispensing or substitutions?

		Is the patient being switched from one product to another? If so, are there any differences in packaging, excipients, devices, or other issues that require counseling?

		What is the scope of state legislation on substitution of interchangeable biosimilars by pharmacy practice setting?

“Our study should reassure clinicians and patients and, importantly, the folks who pay the bills—insurance companies and government programs, like Medicare&mdash;that biosimilar TNF-α inhibitors appear comparable to their branded counterparts based on the evidence we have thus far,” noted Dr. Alexander in the press release. “Hopefully, this will encourage the brisk adoption of these products. There is no question that greater competition in this market will benefit patients, prescribers, and society in the long run.”

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A recent analysis from Johns Hopkins University Bloomberg School of Public Health researchers found that generic forms of the biologic drug infliximab (remicade) appear to be just as safe and effective as the brand name version.

Generic Biologic Drugs Appear Equivalent to Brand Name Counterpart

Generic drug manufacturers have long accused their brand name counterparts of exploiting a federal program intended to promote medication safety as a means of blocking generic competition in the pharmaceutical marketplace.

Risk Evaluation and Mitigation Strategies (REMS) is a relatively new FDA program intended to provide additional safety information to patients and providers. The FDA may require REMS as part of the approval process for a new product, or an approved product with new safety information, to ensure the benefits outweigh the risks.

Many of the products deemed REMS-worthy cannot be purchased or distributed in the normal way. Instead, they must often be distributed by specially certified prescribers and pharmacists. There may be limits on the amount of drug that can be dispensed at said certified locations, and obtaining the product may be contingent on mandatory enrollment and monitoring of patients within registries. Brand name manufacturers have argued that they cannot give generic drugmakers enough samples of these REMS-covered products necessary to conduct the FDA-required bioequivalency testing because doing so would be outside the restricted distribution pathway. Still others claim that brand name manufacturers use REMS in order to artificially extend the market exclusivity for their drugs.

“Misuse of FDA REMS patient safety programs is one way that certain brand-drug companies delay generic competition,” said Chip Davis, president and CEO of the Generic Pharmaceutical Association (GPhA), in a press release earlier this year.3 “Failure to address the loophole that makes these abuses possible is a missed opportunity to encourage more competition in generic drugs and to generate billions of dollars in additional savings for patients and the health system.”

The Senate Judiciary Committee and the Subcommittee on Antitrust introduced a bill, the Creating and Restoring Equal Access to Equivalent Samples (CREATES) Act, that seeks to block pharmaceutical companies from circumventing or otherwise abusing the system to prevent generic competition.

The Congressional Budget Office has estimated that legislation similar to the CREATES Act would save the government over $2 billion in 10 years due to the new generics that would gain entry to the market.

The CREATES Act focuses on undermining 2 strategies sometimes employed by brand name drug manufacturers to block generic competition:

		Sample-sharing, which is when brand name manufacturers prevent potential generic competitors from obtaining samples of the branded drug. This limits the generic company’s ability to perform the testing necessary to show that its generic product is therapeutically equivalent to the branded drug, which is a prerequisite for FDA approval.

		Participation in a shared safety protocol, which occurs when brand manufacturers claim to require a REMS and then refuse to allow generic competitors to participate in that safety protocol, which further blunts generic drugmakers’ abilities to gain FDA approval. If the act were enacted, a generic drugmaker being subjected to either delay tactic would be able to seek injunctive relief in court under the CREATES Act. It would also authorize judges to award damages to claimants in an effort to deter future delay tactics. 

“Unfortunately, we’re seeing some brand name drug companies engage in anti-competitive tactics that delay entry of lower cost generic drugs into the market,” co-sponsor Senator Charles Grassley said in a statement. “This bill takes important steps to ensure that our laws are not frustrated.”

Perhaps the most egregious example of this type of behavior is Turing Pharmaceuticals’ infamous overnight 5000% price hike for the 62-year-old drug Daraprim last September—a move that Turing CEO, Martin Shkreli, told 

 was “not excessive at all.” Daraprim is a standard- of-care drug for life-threatening toxoplasmosis that is also a co-treatment for HIV and malaria. Following the drug acquisition, the price per tablet of Daraprim promptly leaped from $13.50 one day to $750 the next. Then, Turing limited distribution even though the FDA had not required an REMS plan. This hindered manufacturers’ ability to create generic versions of the drug.

Congress has taken previous action against pharmaceutical companies attempting to game the system. The FAST Generics Act, which was introduced in 2014 and then again in 2015, would have closed the aforementioned REMS “loophole”—which refers to a company’s ability to employ restricted distribution networks to block manufacturers’ market entry&mdash;a tactic that initially grew from the REMS Elements to Assure Safe Use (ETASU). If enacted, the legislation would have positioned the Department of Health and Human Services (HHS) to serve as the go-between for the generics industry and brand manufacturers. Generics companies would have sought HHS authorization before submitting a request and authorization to a brand manufacturer.

The CREATES Act takes the effort a step further and was applauded by the GPhA, which, in 2014, produced a study that estimated drugmakers used REMS to thwart competition for $5.4 billion in sales on 40 small-molecule drugs. About 40% of FDA-approved drugs are now subject to REMS. The report cautioned that, if left unchallenged, the impact on the development of lower-cost biosimilars would be substantial.

On the opposite side of the debate, strong REMS advocates allege that the oversight is necessary for drugs known to carry very high risks, and that changes to the system would dilute important safety mechanisms. A blog post on the Health Affairs website, written in support of strong REMS, notes that of the 70-plus drugs now authorized to have unique REMS programs in place, only around 30 are subject to the more restrictive Elements to Assure Safe Use (ETASU) requirements. The post also noted that more than a dozen drugs subject to REMS requirements have gone generic—including 9 with ETASU provisions. This, the blog’s authors allege, serves as evidence that REMS do not impede the development of generics.

Similarly, Holly Campbell, a spokeswoman for the Pharmaceutical Research and Manufacturers of America (PhRMA), told 

, “[REMS] are a critical regulatory tool for protecting patient safety. While we are currently reviewing [the CREATES Act], we would be concerned if patient safety could be jeopardized in any way.”

For patients, quicker access to lower-cost generics could be the difference between adhering to a crucial treatment regimen and forgoing their medications. Steady medication adherence is the key to improving health outcomes, especially for patients with chronic conditions.

Nearly 10% of generic drugs more than doubled in price between July 2013 and July 2014 alone, according to data from the CMS. In the same time period, the price of more than 1200 generic drugs increased by an average of 448%.

 investigated prescribing trends for brand name atorvastatin (Lipitor), generic atorvastatin, and authorized generic atorvastatin. The researchers found that a 6-month delay in the availability of generic versions of Lipitor prevented patients from benefiting from lower out-of-pocket costs.

An accompanying commentary, however, alleged that the 

 findings paint an incomplete picture of patient access to generics. The investigation fails to account for the fact that other generic drugs in the same therapeutic class were available during the study period.

“Although the focus on out-of-pocket costs in the study is important, 1 piece—simvastatin&mdash;is missing,” wrote Walid F. Gellad, MD, MPH, and Chester B. Good, MD, MPH, in the commentary. “In 2006, simvastatin (Zocor, marketed by Merck) lost its patent, and a generic version became available. For many individuals&mdash;and most of the individuals in the cohort studied by Luo et al, of whom only 12.9% had documented coronary artery disease&mdash;simvastatin is appropriate for the treatment of hyperlipidemia.”

The soaring prices for generic drugs are of particular concern for many patients, employers, insurers, and lawmakers, and the CREATES Act may be the most aggressive legislation yet in the pursuit to thwart anticompetitive behavior in the generics industry.

A Brief Overview of Risk Evaluation & Mitigation Strategies (REMS)

. FDA website. www.fda.gov/downloads/AboutFDA/Transparency/Basics/UCM328784.pdf. Accessed July 6, 2016.

		Sarpatwari A, Aaron Kesselheim A. Ensuring timely approval of generic drugs. HealthAffairs website. m.healthaffairs.org/blog/2015/03/24/ensuring-timely-approval-of-generic-drugs. Accessed July 6, 2016.

		Healthcare stakeholders urge senate to end REMS abuse increase generic drug competition [press release]. 

 website. pharmacytimes.com/association-news/healthcare-stakeholders-urge-senate-to-end-rems-abuse-increase-generic-drug-competition. Accessed July 6, 2016.

		Gray N. Lawmakers introduce bill to end REMS abuse, boost generic competition. BioPharmaDive website. biopharmadive.com/news/lawmakers-introduce-bill-to-end-rems-abuse-boost-generic-competition/421043/. Accessed July 6, 2016.

		Brennan Z. New senate bill aims to close regulatory loopholes blocking generic drug competition. Regulatory Affairs Professionals Society website. raps.org/Regulatory-Focus/News/2016/06/15/25135/New-Senate-Bill-Aims-to-Close-Regulatory-Loopholes-Blocking-Generic-Drug-Competition. Published June 15, 2016. Accessed July 6, 2016.

		Grassley works to combat rising drug prices for Iowans. Chuck Grassley website. grassley.senate.gov/news/news-releases/grassley-works-combat-rising-drug-prices-iowans. Accessed July 6, 2016.

		Gilchrist A. Turing Daraprim price hike follows a precedent. 

 website.  pharmacytimes.com/news/turing-daraprim-price-hike-follows-a-precedent. Accessed July 6, 2016.

		Gilchrist A. FAST Generics Act Reintroduced in Congress. 

 website. pharmacytimes.com/publications/issue/2015/september2015/fast-generics-act-reintroduced-in-congress. Accessed July 6, 2016.

 Lost Prescription Drug Savings from Use of REMS Programs to Delay Generic Market Entry

. Generic Pharmaceutical Association website. gphaonline.org/media/cms/REMS_Studyfinal_July2014.pdf. Accessed July 6, 2016.

		Worthy S, Curtis S. In ‘ensuring timely approval of generic drugs,’ safety must come first. Health Affairs Blog. healthaffairs.org/blog/2015/05/14/in-ensuring-timely-approval-of-generic-drugs-safety-must-come-first. Accessed July 6, 2016.

		Gilchrist A. Effort to curb rising generic drug costs reaches Congress.

 website. pharmacytimes.com/publications/issue/2015/july2015/effort-to-curb-rising-generic-drug-costs-reaches-congress. Accessed July 6, 2016.

		Luo J,  Seeger JD,  Donneyong M,  Gagne JJ,  Avorn J,  Kesselheim AS. Effect of generic competition on atorvastatin prescribing and patients’out-of-pocket spending. 

 website. archinte.jamanetwork.com/article.aspx?articleid=2530416. Published June 27, 2016. Accessed July 6, 2016.

		Gellad WF, Good CB. Prescription of brand-name medications when generic alternatives are available—patently unfair.

 website. archinte.jamanetwork.com/article.aspx?articleid=2530415. Published June 27, 2016. Accessed July 6, 2016.

Generic drug manufacturers have long accused their brand name counterparts of exploiting a federal program intended to promote medication safety as a means of blocking generic competition in the pharmaceutical marketplace. 

Stakeholders Take Aim at Generic Competition Blocking Tactics

The Supreme Court of the United States (SCOTUS) recently ruled in favor of generic drug manufacturers and advocates for lower drug prices in a patent-law case, the result of which, brand name manufacturing stakeholders argue, hinders continued investments in vital drug research and development. The case, 

, was not, technically, about prescription medications. Rather, the case focused on an invention that alerts drivers when they are driving over the speed limit. Nevertheless, several drug industry groups weighed in on the case in briefs, noting that the decision could have major implications for them and consumers because “meaningful patent protection is required to justify” investments in drug development.

At the heart of the issue is the inter partes review (IPR) process, which first came into effect in September 2012. Through IPR, judges, employed by the US Patent and Trademark Office, review patent challenges that would otherwise be heard in longer court proceedings. The IPR process is cheaper and faster than the federal court system and has become a favorite dispute resolution avenue for generic drug companies. The procedure for complaints, established under the Hatch-Waxman Act and the Biologics Price Competition and Innovation Act (BPCIA), takes an average of 30 months to review and issue a ruling in a patent case, whereas the IPR system has historically solved challenges in about 15 to 18 months.

A 2015 analysis from the Congressional Budget Office (CBO) estimated that a change to the IPR process and patent laws sought by brand name pharmaceutical industry stakeholders would add $1.3 billion in costs over 10 years to the US health care system by delaying generic drugs’ entry to the market. Although the faster resolution time is the basis for the CBO’s assumption that delayed proceedings would add costs, both the Pharmaceutical Research and Manufacturers of America (PhRMA) and the Biotechnology Industry Organization (BIO) disagreed with the CBO estimates because there is no direct evidence that suggests the IPR process actually helps bring generics to market more quickly.

In the past, brand name pharmaceutical companies have alleged that IPR has been used as a vehicle to circumvent the legal framework that already exists in the Hatch-Waxman and BCPIA language. The Coalition for Affordable Drugs, led by hedge fund manager Kyle Bass of Hayman Capital, challenged more than 20 patents in 2015 on behalf of generic manufacturers. Additionally, brand manufacturers have alleged, the IPR system harms the investment climate for pharmaceuticals. Investors are discouraged by the fact that patents can be challenged through both the IPR system and the federal courts, concurrently. They argue that this threat can stunt innovation, which, in turn, affects patients and access to new medicines.

This coalition of pharmaceutical trade groups, led by PhRMA and BIO, asked Congress and, ultimately, SCOTUS, to consider exempting drug patents from facing challenges via the IPR process. PhRMA filed an amicus brief during the SCOTUS proceedings. “Uncertainty regarding the scope of patent claims and their validity is costly to the inventive community and discourages innovation,” PhRMA wrote in its brief.

PhRMA also noted that, in prior cases before the patent board in which a broader standard was applied, 87% of final decisions found at least some claims “unpatentable.” Meanwhile, in federal court, where the narrower standard is used, the group noted that those challenging patents’ validity won 42% of the time.

America’s Health Insurance Plans (AHIP) and Generic Pharmaceutical Association (GPhA) jointly filed an amicus brief addressing the IPR process in promoting a competitive, affordable prescription drug market for consumers.

In the unanimous opinion, authored by Justice Stephen Breyer, “The Patent Office’s regulation is reasonable,” Breyer wrote, “and this Court does not decide whether a better alternative exists as a matter of policy.”

Meanwhile, generic drug industry groups lauded the Court’s opinion as a win for both consumers and drug industry stakeholders.

“Today’s decision from the Supreme Court is a significant win for consumers. By protecting and reaffirming the importance of the inter partes review, the court recognizes the vital need for an efficient patent review process—one that promotes a competitive, affordable prescription drug market for consumers,” said AHIP President and CEO Marilyn Tavenner, and GPhA President and CEO Chip Davis, in a joint statement.

PhRMA said that it was “disappointed” in the ruling. “This dual standard threatens the predictability and strength of the protections that the patent system is supposed to provide to innovators,” the group said in a press release.

The SCOTUS opinion comes amid heightened scrutiny over prescription drug costs in the United States.

The Supreme Court of the United States recently ruled in favor of generic drug manufacturers and advocates for lower drug prices in a patent-law case, the result of which, brand name manufacturing stakeholders argue, hinders continued investments in vital drug research and development. 

Supreme Court Opinion Delivers Blow to Drug Patent Holders

Just as no 2 patients with type 2 diabetes (T2D) are alike, no 2 diabetes support programs should be the same, either.

Diabetes is a complex condition that requires various treatment and education strategies to achieve goals beyond glycemic control. 

 in diabetes management are maintaining adequate lifestyle habits, diabetes self-management education, and prevention of diabetic complications.

A core issue facing today’s T2D patients is the daunting task of tracking countless glucose readings, lab tests, medication compliance, insulin dosing, appointments, dietary intake, exercise activities, and recommendations given by various health care providers.

Fortunately, a free online program called Fit2Me allows T2D patients to tailor 4 key areas of diabetes care to their specific needs:

Patients can flip through different types of cuisine, including Mexican, Italian, or Asian, and choose their favorites. Fit2Me then provides recipes based on cooking habits and preferences. The program boasts more than 10,000 diabetes-friendly recipes.

Fit2Me users have access to advice on how to burn calories without having to go to the gym. Patients only need to enter in their current activity level, and then the program can offer exercise lessons via instructional videos.

Fit2Me provides medication reminders to help patients stay on top of their treatment. Users can also record their blood sugar levels and track their progress toward their A1C goals.

T2D patients who use Fit2Me have the opportunity to choose their own digital coach based on personality preferences. They also have access to T2D diabetes-trained nurses and counselors. Those who meet milestones in their personal progress goals are also eligible to win cool rewards. 

A free online program called Fit2Me allows T2D patients to tailor 4 key areas of diabetes care to their specific needs