News & Events

ComputerTalk for the Pharmacist July/August 2017

PHSI President Tim Kosty contributed to the July/August 2017 edition of ComputerTalk for the Pharmacist. In his Viewpoints article, Tim explores the historical issues with DUR system configurations and suggest steps the industry needs to take to improve patient safety.

Click here to read Tim’s article entitled “Drug Utilization Alerts: Failures and Future Direction”. You can read full versions of current and past ComputerTalk issues at http://www.computertalk.com/issues-archive.

2017 Summer Newsletter- FDA Orange Book Added Identifier

FDA Orange Book Added Identifier

Prior to 2017, the FDA’s “Approved Drug Products with Therapeutic Equivalence Evaluations” (Orange Book) used the Reference Listed Drug (RLD) identifier for different uses, depending upon the market situation.  These uses included the RLD identifying the NDA or an ANDA (when the NDA was no longer marketed or other extraordinary situations) that would identify the product to compare for bioequivalence.  The RLD was also used as the standard for generics to use for pharmacokinetic testing when preparing for an ANDA submission.

In this scenario, when an ANDA was identified as the RLD, the FDA clarified which product prospective ANDA applicants should use for bioequivalence testing as the reference standard.  This change created new issues because the ANDA applicant knew which product to conduct their pharmacokinetic testing, but there was no longer a NDA to use as the basis of generic labeling.  This caused confusion for ANDA applicants because the RLD identifier was being used to determine the “reference standard” (RS), which may not have been the basis for product labeling.

In 2017, the FDA updated the Orange Book to split the RLD identifier into the two unique definitions.  The RLD now solely refers to the application and labeling aspect the ANDA applicant should reference. The RS determines the product to conduct the bioequivalence testing.  In many cases, the RLD and RS are the same product.  The separate identifiers can be used to clearly delineate the focus for the applicant’s labeling vs. the bioequivalence testing.

FDA Orange Book Examples May 2017

Januvia, a single source brand, depicts the scenario in the Orange Book where only the brand is listed and available.  Januvia is both the RLD and RS reference product.

Summer NL 1

Darifenacin (generic Enablex) demonstrates that the NDA will continue to be identified as the RLD and RS as long as it is marketed.

Summer NL 2

The RLD can identify a discontinued NDA product, while the RS can identify an active ANDA so the ANDA applicant can clearly determine the comparison application for labeling (RLD) and the comparison application for pharmacokinetic studies (RS).

This second scenario is found with Cefaclor oral suspension.  The active ANDA is the RS, and the discontinued NDA, Ceclor, is the RLD.  Prior to the FDA change in 2017, the ANDA would have been identified as the RLD instead of the discontinued NDA.

Summer NL 3

The reference standard (RS) in the FDA Orange Book is a new identifier on certain products and depicts which product the applicant should use for bioequivalence testing.  The new RS identifier is not currently found in the drug compendia, but must be referenced in the FDA Orange Book.  The RLD now is solely focused on identifying the product to reference the labeling.  ANDA applicants now have clarity from the FDA for labeling (RLD) and product source for pharmacokinetic testing (RS).

 

2017 Summer Newsletter- 2018 Drug Exclusion Lists

2017 Summer Newsletter- 2018 Drug Exclusion Lists

Express Scripts and CVS Health 2018 Drug Exclusion Lists

Express Scripts and CVS Health have released their highly anticipated formulary exclusion lists for 2018.  Although CVS Health states that they will not finalize their list until September 15, they have published the expected formulary exclusions, indicating  that the autoimmune and hepatitis C categories may change.  PHSI analyzed the exclusion lists to note trends and changes over time.  Including combination products (e.g. Benicar and Benicar HCT), CVS Health added 21 products to their exclusion list, while Express Scripts added 68 drugs.  With many blockbuster drugs losing brand exclusivity in the past few years, it is not surprising that the 2018 exclusions lists are rife with multi-source brand products.

Of the 68 drugs added to Express Scripts’ formulary exclusion list, 50 were multi-source brands.  Meanwhile, eight of CVS’s twenty-one exclusions have generic alternatives available.  On both the CVS Health and Express Scripts’ lists, commonalities exist with both PBMs adding Effexor XR, Seroquel XR, Zetia, and Benicar/Benicar HCT to their exclusion lists.  Because lower-cost generics are now readily available for these products, excluding these brands will lower costs.

Specialty drugs may be the new frontier of drug innovation and account for the majority of new product launches.  See PHSI’s previous newsletter article, “2016: The Decline of New Drug Approvals and Increase in Expedited Reviews”.  However, specialty drugs were not overly abundant on the 2018 exclusion lists.  Both CVS Health and Express Scripts each added four specialty drugs to their 2018 exclusion lists.  CVS added Elelyso, Follistim, Synvisc, and Synvisc One, while Express Scripts added Sandostatin LAR Depot, Signifor LAR, Neupogen, and Forteo.

For Express Scripts, one of the most interesting exclusions was epinephrine auto-injectors from A-S Medication, Impax, and Lineage.  Express Scripts appears to have partnered with Mylan to promote the EpiPen and generic Mylan epinephrine auto-injector, which are the preferred alternatives.  CVS Health does not include either the EpiPen or generic epinephrine auto-injectors on their exclusion list.  However, in the past year, CVS retail stores have been promoting their low cash price epinephrine program, which provides the Impax/Lineage epinephrine product to patients for approximately $110.  Based on the success of that program, it is not unusual to see the epinephrine market divided amongst the PBMs (CVS and Express Scripts) and manufacturers (Mylan and Impax/Lineage).

New exclusions were not the only changes seen on the 2018 lists.  CVS announced that 18 products are being removed from the exclusion list, perhaps due to shifting costs or increased rebates from brand manufacturers.  Of the 18 items being re-added to the formulary, 13 will be placed on a preferred drug tier, while the remaining five will be placed on a non-preferred tier.  The items being removed from the exclusion list are shown in the chart below.

2018 Exclusion List Removals

Based on prior exclusions, Express Scripts notes that a total of 159 drugs are now included on their formulary exclusion list.  Meanwhile, CVS appears to have approximately 180 products on their exclusion list, although this may change when the autoimmune and hepatitis C categories are finalized mid-September.  It will be interesting to watch the exclusion list changes in coming years, especially as biosimilars become more prevalent.

The chart below lists new products on the CVS Health and Express Scripts 2018 drug exclusion lists that were not present on the 2017 lists.

2018 Exclusion List

 

2017 Summer Newsletter- FDA Orange Book Added Identifier

Tim Kosty Presented on Drug Utilization Edits at ASAP Midyear

PHSI President Tim Kosty presented on “Drug Utilization Edits: Failures, Needs, and Future Direction” at the American Society for Automation in Pharmacy (ASAP) 2017 Midyear Conference. Tim’s presentation reviewed a variety of issues, including historical implementation of DUR edits, pharmacy workflow considerations, choices made by pharmacy chain management to display/suppress messages, payers’ choices on DUR messaging in their claims processing systems, legal implications, and future strategies and tactics. Click here to view Tim’s presentation slides. You can access all of the 2017 ASAP Annual Conference presentations at http://www.asapnet.org/2017-midyear.html

ComputerTalk for the Pharmacist May/June 2017

PHSI Consultant Dave Schuetz contributed to the May/June 2017 edition of ComputerTalk for the Pharmacist. In his Viewpoints article, Dave discusses the concern that the NDC (National Drug Code) number is going to run out of numbers sometime in the next decade and the need for industry stakeholders to start the discussion and work toward a goal before it’s too late.

Click here to read Dave’s article entitled “What Happens When We Run Out of NDC Numbers?”

PHSI to Attend NACDS Total Store Expo

PHSI President Tim Kosty, Vice President Don Dietz, and many of PHSI’s consultants will be attending the 2017 NACDS Total Store Expo in San Diego, CA on August 19-22. PHSI will have an exhibit set up at booth number 2837. If you would like to schedule a meeting with a PHSI team member, please click here to send us a message.

To learn more about this conference, visit the Total Store Expo website at http://tse.nacds.org

ComputerTalk for the Pharmacist January/February 2017

PHSI President Tim Kosty and Vice President Don Dietz contributed to the January/February 2017 edition of ComputerTalk for the Pharmacist. In their Viewpoints article, Tim and Don provide a forecast of market changes for 2017. The article reviews topics related to industry challenges, preferred pharmacy networks, driving pharmacy efficiency, clinical services, and industry consolidation.

Click here to read their article entitled “The Outlook for 2017”.

Conflicts with Value-Based Medication Pricing

With multiple diverse variables and stakeholders to consider, controlling healthcare expenditures has proven to be a difficult problem to solve. Recently, the American Medical Association has voiced support for Value-Based Medication Pricing. This means that a drug would be priced based on the benefit to the patient’s care. While this may seem like a promising strategy, there are several concerns that arise under value-based pricing. For instance, generic drugs often provide high levels of care but do not fall under high price brackets. Under a value-based system, would the prices increase to reflect the value of a low-cost antibiotic? Also, many nonessential prescription products do not make it onto an insurance formulary, including various topical products that are mostly used for cosmetic purposes. This means that the value is much more personal to the patient. The ambiguity in value makes it extremely difficult to establish a value-based price.  In value-based pricing, the payer is the stakeholder defining value.  Another concern that is often brought up when discussing drug costs is research and development.  Often, profits in pharmaceutical manufacturing are used to fund research and development for new innovative medications. Many fear that drastically changing the way medications are priced could hinder new drugs coming to market. Time will tell if value-based pricing attracts more attention but both arguments highlight the fact that coming up with a strategy to price medications is no easy task.

 

http://insidepatientcare.com/issues/2016/december-2016-vol-4-no-12/449-value-based-medication-pricing

2017 Winter Newsletter- Biosimilar Interchangeability

FDA Draft Guidance on Demonstrating Interchangeability

This January the FDA published draft guidance entitled, “Considerations in Demonstrating Interchangeability with a Reference Product”.  This long-awaited guidance provides biosimilar manufacturers with information on proving and supporting their claims of interchangeability status when submitting a 351(k) application.  The draft guidance indicates that biosimilars will require physician approval before pharmacy substitution, unless they gain interchangeability status.  Interchangeable products may be substituted at the pharmacy without prescriber approval or notification.  Just as small molecules must prove both pharmaceutical equivalence and bioequivalence to be considered therapeutically equivalent and substitutable (i.e.: FDA Orange Book A-rated), 351(k) products must show biosimilarity, clinical equivalence, and switchability to be considered interchangeable.

In order to be considered interchangeable to the reference product, the applicant must show that:

  1. Their biological product is biosimilar to the reference product
  2. Their product can be expected to produce the same clinical result as the reference product in any given patient for all indications
  3. For a biological product that is administered more than once to an individual, the risk in terms of safety or diminished efficacy of alternating or switching between the biological product and reference product is not greater than the risk of using the reference product without an alternation or switch

To prove that the product can produce equivalent clinical results, manufacturers must provide data on critical quality attributes, mechanisms of action (target receptors, receptor binding, dose response, etc.), pharmacokinetics, biodistribution, immunogenicity, toxicities, and many other factors.  With scientific justification, manufacturers can extrapolate clinical data to support interchangeability status for additional drug indications.  Although products may be approved as biosimilars if only applying for approval for one reference product indication, interchangeable products must be clinically equivalent and switchable for all indications of the reference product.

In addition to clinical studies, manufacturers must demonstrate the ability of their biosimilar to be switched back-and-forth with the reference product.  The FDA states that they expect applicants to include information from switching studies that mimic appropriate conditions of use.  The newly published draft guidance provides conditions for manufacturers to consider when designing a switching study, including study endpoints, analysis, population, routes of administration, and conditions of use.  The guidance notes that in general, post-marketing data would be insufficient to prove the impact of product switching and would not be enough to gain interchangeability status.  The FDA did state that post-marketing surveillance may be needed along with switching studies to demonstrate interchangeability if there is “residual uncertainty”.  If this draft guidance is finalized as is, it would mean that some biological products must be initially approved as biosimilars and can only gain interchangeability status after a time period significant enough to allow for post-marketing surveillance (likely several months to years).

Throughout the draft guidance, it is recommended that manufacturers work closely with the FDA to discuss their proposed switching studies and proposed presentation, i.e. product packaging, (vial, pre-filled syringe, auto-injector, etc.).  The FDA recommends that manufacturers only seek interchangeability status for products with the same presentation.  They also suggest that manufacturers discuss any proposed presentation changes with the FDA, as the presentation and its design will be thoroughly analyzed prior to granting interchangeability status.

The clinical data and additional study requirements necessary to prove interchangeability for 351(k) applicants will prove more burdensome and expensive than proving substitutability for traditional generic ANDA approvals.  With the amount of data needed to substantiate interchangeability status, there will be a much larger investment to bring an interchangeable product to market compared to a small molecule.  It is not surprising that biosimilars are expected to only provide 30% savings over their reference product.  As expected, the FDA places emphasis on the importance of post-marketing safety monitoring for biosimilar and interchangeable products.  The full 30-page draft guidance document can be found here.  PHSI recommends that all stakeholders monitor this guidance closely, as finalized guidance will have a tremendous impact on the future of biosimilars.

 

2017 Winter Newsletter- 2016 New Drug Approvals

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2017 Winter Newsletter- 2016 New Drug Approvals

2016: The Decline of New Drug Approvals and Increase in Expedited Reviews

According to the FDA, only 22 novel new drugs were approved in 2016.  This is a 50% decrease from 2015.  Novel drugs, or new molecular entities, are defined by the FDA as “products containing active moieties that have not been approved by FDA previously, either as a single ingredient drug or as part of a combination product.”  After two record-breaking years of new drug approvals, 2016 is a bit of a letdown for prescribers and patients hoping for new, innovative therapies.  Last year was the lowest number of novel new drug approvals since 21 drugs were approved in 2010.  The chart below shows the trend in the number of new drug approvals for the last six years.

Novel Drug Approvals

Similar to 2015, the largest number of products approved in 2016 were indicated to treat different types of cancers.  For example, Lartruvo was approved to treat soft tissue sarcoma; Rubraca treats ovarian cancer.  Venclexta is indicated for chronic lymphocytic leukemia, and Tecentriq treats bladder cancer.

All of these oncology agents were breakthrough therapies that received FDA priority reviews and accelerated approvals due to the positive implications for patients.  When reviewing all 2016 approvals, priority review is the new norm vs. the exception, as 68% of all 2016 approvals had a priority review.  This could also indicate that few manufacturers are pursuing follow-on drugs in therapeutic categories that already have multiple available drugs.

Based on 2015 and 2016 approvals, special distinctions and expedited approvals from the FDA appear to be becoming more common.  The FDA defines these distinctions as:

First-in-Class: Drugs having mechanisms of action different from those of existing therapies (36% of 2016 approvals)

Drugs for Rare Diseases: Drugs approved to treat rare or “orphan” diseases affecting 200,000 Americans or less (41% of 2016 approvals)

Fast Track: Drugs having the potential to address unmet medical needs (36% of 2016 approvals)

Breakthrough: Drugs with preliminary clinical evidence demonstrating that the drug may result in substantial improvement on at least one clinically significant endpoint versus other available therapies (32% of 2016 approvals)

Priority Review: Drugs are reviewed within six months instead of the standard ten months if the drug could potentially provide a significant advance in medical care (68% of 2016 approvals)

Accelerated Approval: Approval is based on a “surrogate endpoint”, such as a lab value or clinical measure, that the FDA considers reasonably likely to predict the drug’s clinical benefit and allows for earlier approval for drugs treating serious or life threatening illness that offer a benefit over current treatments (27% of 2016 approvals)

The same drug may fall into multiple categories.  The chart below summarizes the 2016 novel drug approvals with special distinctions and/or expedited approvals, as noted by the FDA.

2016 also saw a number of first-time generic launches.  The biggest generic launch of the year was generic rosuvastatin (Crestor).  Other notable brands losing patent protection and becoming availability generically included Benicar (olmesartan), Tamiflu (oseltamivir), and Zetia (ezetimibe).  There were a few notable generic specialty launches in 2016 including imatinib (Gleevec) and valganciclovir (Valcyte), reducing the cost for patients taking these medications.  Although generics are now more common in the specialty space, brand drugs still dominate specialty pharmacy, and PHSI estimates that only 6 of the 22 new drug approvals are traditional retail pharmacy products.

As 2017 unfolds, look for more of the 2016 approvals to become commercially available and appear on drug formularies.  Due to high costs and limited patient population sizes, we anticipate many of these agents being placed on specialty drug tiers due to the high rate of 2016 approvals for drugs treating rare disease states.  PHSI expects this trend to continue in 2017 and will report on the new approvals and their effects on the industry.

 

2017 Winter Newsletter- Biosimilar Interchangeability

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