On January 31, 2018, the European Commission adopted a legislative proposal with the aim of strengthening EU cooperation among Member States when conducting a Health Technology Assessment (HTA) of new medicines and certain new medical devices. The European Commission Fact Sheet explains that HTA is a procedure for assessing the added value of new medicines and medical devices, for example, assessing whether a new scanner will lead to a better diagnosis or whether a new surgery will improve the patient’s treatment.
BEUC, the European Consumer Organization, explained in a press release that at the moment, around 50 national and regional HTA authorities provide Member States with clinical data, however, work carried out by one authority is often replicated by another, leading to inefficiency in EU health systems.
The Commission’s proposal establishes four areas of joint work between Member States at EU-level:
- Joint clinical assessments focusing on the most innovative health technologies with the most potential impact for patients;
- Joint scientific consultations, or “early dialogue,” whereby developers can seek advice from HTA authorities;
- Identification of emerging health technologies, commonly referred to as ‘horizon scanning’, to identify promising technologies early; and
- Voluntary cooperation on other areas.
In a press release, the Commission added that “manufacturers will no longer have to adapt to different national procedures.” Not all work will be done jointly, the Commission’s press release indicates that individual EU countries will continue to be responsible for assessing non-clinical (e.g. economic, social, ethical) aspects of health technology, and making decisions on pricing and reimbursement. Thus, device manufacturers will still need to work with each Member State to determine pricing and reimbursement.
The Commission’s Q&A on the proposal explains that the joint clinical assessments will not affect market approval as they will only occur after the medical devices have obtained a CE mark. The Q&A also notes that HTA does not interfere with the conformity assessments of medical devices.
The Commission asserted in the Q&A that those benefiting from cooperation would include:
- Patients, who may benefit from a faster uptake of promising innovative technologies;
- Member States, whose national authorities will be able to pool their expertise and avoid duplication of efforts on clinical assessments, making better use of human and financial resources; and
- Industry, including SMEs, who will benefit from clearer rules and greater predictability for their business planning, and cost savings.
In a statement to EURACTIV.com, Yannis Natsis, Policy Manager for the European Public Health Association, cautioned:
A European approach must improve on the current system and deliver meaningful innovation and affordable treatments. There must not be the slightest doubt that cooperation would weaken it or make the assessments less rigorous.
A timeline proposed by the Commission indicates that the proposal could be adopted by the European Parliament and the Council of Ministers in 2019, become applicable three years later, and then have a further three-year transitional period to allow for Member States to phase-in the new system. The Q&A provides an example of a phase-in, suggesting the system could perform 10 to 15 joint clinical assessments in the first year of operation and reach around 65 assessments towards the end of the transitional period. The changes will likely happen after Britain has exited the European Union.
District Court Awarded Ultrasound Device Maker Verasonics $5.6 Million And World-Wide Injunction In Trade Secret Case
The United States District Court of Western District of Washington entered a judgment in a trade secret case, Verasonics, Inc. v. Alpinion Medical Systems Co., Ltd. (Case No. 2:14-cv-01820-JCC). The district court confirmed the final arbitration award, giving Plaintiff Verasonics, Inc. $5.6 million in damages, including fees and costs, and enjoining Defendant Alpinion Medical Systems Co., Ltd. from using Verasonics’ trade secret, including marketing or selling any devices using the trade secret for five years.
Verasonics, Inc. describes itself as a Kirkland, Washington-based company that specializes in ultrasound devices and technology. In the complaint filed on November 26, 2014, Verasonics alleged that Alpinion, headquartered in Seoul, South Korea, showed interest in “licensing, co-development or investment” opportunities with Verasonics starting from 2010. Alpinion allegedly “induced” Verasonics into revealing its trade secrets and confidential information to Alpinion as the two parties entered into a series of Non-Disclosure Agreements (“NDAs”), and lease agreements for Alpinion to lease two research ultrasound systems from Verasonics. The complaint also alleged that Alpinion made a below-market offer to Verasonics, which was rejected, and that Alpinion represented that its interest was in commercial ultrasound products, not in research ultrasound devices.
However, Alpinion later announced its own eCube-12R ultrasound platform specifically designed for the research market. Verasonics sued Alpinion for trade secret misappropriation under the Washington State Uniform Trade Secret Act in addition to breach of contract claims in the Western District of Washington.
In 2015, the case at the district court was stayed pending a binding arbitration at the American Arbitration Association (case name ICDR No. 01-15-0002-9484). The arbitrator found that Alpinion breached the parties’ NDAs and lease agreement, and violoated the Washington Uniform Trade Secret Act. The arbitrator issued a partial final arbitration award of $2.9 million in compensatory damages and a five-year injunction against Alpinion on March 2, 2017. The partial arbitration award was filed under seal and not publicly available. According to Davis Wright Tremaine LLP, the law firm representing Verasonics in this matter, the injunction against marketing and sales of the accused product is worldwide. The arbitrator subsequently issued a final award on June 26, 2017, ordering Alpinion to pay Verasonics another $2.7 million in attorneys’ and arbitration fees and other expenses.
According to a press release made after the partial final award, Lauren Pflugrath, president and CEO of Verasonics, said:
We are grateful for the arbitrator’s decision to issue the Final Award so clearly in our favor. We continue to expand and build positive collaborative partnerships, but must insist on protecting our intellectual property.
Wright Medical Group recently announced the acquisition of IMASCAP SAS for $88 million. According to the press release, Wright Medical Group (NASDAQ: WMGI) is a publicly traded company focusing on extremity joint replacement and bio-orthopedic material development. IMASCAP SAS focuses on developing software for preoperative joint replacement surgery.
According to the press release, the companies have had a previous relationship where Wright Medical Group used IMASCAP’s Genosys technology in its BLUEPRINT 3D planning software. The technology is said to allow surgeons to visualize potential movement in a shoulder joint so as to determine the best type of implant to use. The program is reported to use data provided entirely from a computed tomography scan. The press release notes that using the program allows surgeons to save time during surgery by adjusting their strategy beforehand. Since Genosys’s release in 2014, the company lists its use in 3800 pre-operative planning procedures, by over 1000 surgeons, in 21 countries .
The press release notes that the deal includes approximately $46.9 million in cash, $15.6 million in ordinary shares, and approximately $26.3 million, in potential earnouts and milestone payments for new software and implant systems.
In the press release, Robert Palmisano, President and Chief Executive Officer of Wright Medical Group, stated, “Software-enhanced solutions are the future, and with the acquisition of IMASCAP, we have the opportunity to take a significant lead in this area”.
In a statement by IMASCAP’s Jean Chaoui, President and Chief Executive Officer, “We believe that Wright, with its global leadership position in the extremities market and expertise in medical education and product development, is the ideal partner to realize the full potential of IMASCAP’s technology and product pipeline”.
In its press release, Wright Medical Group also expressed interest in a variety of other technologies under development that could potentially help the company expand into other joint replacement areas. Currently, the company has plans to offer the software free of cost to physicians currently using its shoulder joint replacement technology.
BioArctic Announces Patent Allowance Entitled Spinal Cord Devices and Methods for Promoting Axonal Regeneration
BioArctic AB, a public Swedish biopharma company, recently announced that they received allowance of a patent application directed to a method of promoting axonal regeneration using a biodegradable spinal cord device. The medical device is said to be a component of BioArctic’s SC0806 product for treatment of complete spinal cord injury. The allowed claims are directed toward “selecting a spinal cord device” having certain geometric characteristics, “positioning peripheral autologous nerves in … through channels,” and implanting the device in an injured spinal cord. The device is said to be soakable in a solution of FGF1 growth factor prior to implantation. BioArctic reports to have received corresponding patents in China and Australia.
According to BioArctic, despite considerable research into bridging spinal cord gaps, no product is yet available on the market. BioArctic states that the SC0806 spinal cord product is currently undergoing Phase 1/2 clinical trials in Sweden and was granted orphan drug status in the European Union and the United States, qualifying the product for 10 and 7 years of market exclusivity, respectively. The product received funding from the European Union’s Horizon 2020 Research and Innovation Program, the EU’s largest public investment program for research and innovation, comprising an €80 billon investment over 7 years, culminating in 2020.
According to BioArctic, in addition to developing treatments for complete spinal cord injury, its research focuses on disease modifying treatments and reliable biomarkers and diagnostics for neurodegenerative diseases, such as Alzheimer’s disease and Parkinson’s disease, for which AbbVie has agreed to develop and commercialize BioArctic’s Parkinson’s antibody portfolio. European Biotechnology rated BioArctic’s €71.8 million IPO as one of Europe’s most successful in 2017.
Tel Aviv-based MedyMatch Technology recently announced it has received Expedited Access Pathway (EAP) designation from the FDA for its intracranial hemorrahage (ICH) detection software medical device.
According to Gene Saragnese, Chairman & CEO of MedyMatch, the platform is a “first-in-class hemorrhage detection tool.” The MedyMatch device utilizes artificial intelligence and deep learning technologies to analyze non-contrast head CT images for signs of ICH. Further implementations of the MedyMatch deep vision platform include diagnosis and monitoring of acute and chronic diseases based on concurrent analysis of imaging data and other patient data. Vice President of Clinical, Regulatory, and Quality Affairs, Dr. Joshua Schulman, said:
This designation is a recognition of both the need for new assessment tools for intracranial hemorrhage and an affirmation of MedyMatch’s technical approach to assisting clinicians to need to make time-sensitive yet accurate decisions in emergency settings.
The EAP Program, intended to speed approval of certain medical devices, generally includes priority review, more interactive review, and senior management involvement. EAP designation can be awarded for devices that address unmet needs for treatment or diagnosis of life-threatening or irreversibly debilitating conditions. It is said to be expected that EAP designated devices will be transitioned to the new Breakthrough Devices program established under the 21st Century Cures Act of 2016.
On January 22, 2018, a $50 million lawsuit was filed against the U.S. Food and Drug Administration (FDA) in the Central District of California. The complaint was filed by Semler Research Center Pvt. Ltd., a contract research organization based in Bangalore, India.
The suit comes after the FDA notified a number of drug makers that marketing applications containing clinical trial data prepared by Semler would not be accepted due to concerns about the integrity of the data.
According to the FDA notification, the FDA inspected Semler facilities last fall. After the inspection, the FDA posted a notice on its web site saying that inspections found “significant instances of misconduct and violations of federal regulations, including the substitution and manipulation of study subject samples.”
According to the complaint, FDA inspectors ignored evidence that a “rogue employee” framed Semler by planting false data on the company’s computer network.
The complaint alleges that those employees were part of a scheme that involved contacting the FDA “to lead FDA inspectors to the fabricated information and raise suspicion regarding [Semler’s] procedures and the reliability of its studies.”
According to Semler, an independent audit showed that the purported data manipulation could not have occurred in the manner suggested by the suspect spreadsheet. Nonetheless, FDA officials “summarily disregarded the results” of the audit and produced the disciplinary letter.
According to Semler’s complaint, in response to the FDA’s actions, a $30 million sale of Semler collapsed, and various Semler clients are “demanding compensation” worth $20 million.
Semler’s lawsuit alleges violations of its Fifth Amendment right to due process, as well as intentional infliction of financial distress under the Federal Tort Claims Act, among other things.
The case is Semler Research Center Pvt. Ltd. v. U.S. Food and Drug Administration et al., case number 2:18-cv-00534, in the U.S. District Court for the Central District of California.
Boston Scientific Announces Agreement for Investment & Acquisition Option with Transcatheter Annuloplasty Ring Developer Millipede, Inc.
Global medical device company Boston Scientific has announced on January 24, 2018, an agreement to make a $90 million investment in privately-held medical device company Millipede, Inc. Millipede has developed a non-invasive solution for repair of the heart’s mitral valve. According to the press release, the agreement includes an option for Boston Scientific to acquire all remaining shares of Millipede, upon completion of a clinical study, for an additional $325 million in cash, with an extra $125 million in payments upon completing a commercial milestone.
According to Millipede’s website, Millipede’s IRIS Transcatheter Annuloplasty Ring System reshapes the mitral valve annulus of the heart to treat severe mitral regurgitation (MR). MR is caused by a leaking mitral valve, which causes blood to flow backward from the left ventricle into the left atrium. Over time, MR can lead to or accelerate heart failure and rhythm problems. Millipede’s website describes the IRIS system as providing the gold standard in surgical heart valve repair – a complete annuloplasty ring implant. The implant reshapes and reduces the mitral valve annulus opening, enabling return of leaflet coaptation and reduction of MR.
According to Millipede, the implant is delivered via catheter, for example through a small cut in the patient’s leg. This allows patients to avoid invasive open heart surgery, which is necessary for implantation of conventional annuloplasty rings. Millipede describes the transcatheter ring as repositionable and retrievable.
“We saw an opportunity to bring the gold-standard surgical approach to repairing the mitral valve to an underserved population of severe MR patients with transcatheter techniques, and are excited Boston Scientific also sees the unique abilities of the IRIS transcatheter ring” – Joe Cunningham, MD, Chairman of the Board, Millipede, Inc. and Managing Director of Santé Ventures.
Millipede is based in Santa Rosa, California and was founded in 2012 by majority investor Santé Ventures and Steve Bolling, MD, and has been led by CEO Randy Lashinski since 2014.
Boston Scientific describes itself as a worldwide developer, manufacturer and marketer of medical devices, providing a broad range of high performance solutions that address patient needs and aim to reduce the cost of healthcare.
Millipede is a client of intellectual property and technology law firm Knobbe Martens. With over 275 lawyers and scientists nationwide, Knobbe Martens dedicates its practice to all aspects of intellectual property law including litigation and is consistently ranked among the top intellectual property firms worldwide.
Da Volterra, a biotech company developing products in the antibacterial field, has announced results in a human clinical trial for DAV132, a product said to prevent life-treating bacterial infections during antibiotic treatments.
According to Da Volterra, many orally administered antibiotics are only partially absorbed in the upper intestinal tract upon ingestion, and much of the administered drug passes into the lower intestinal tract. These drugs can then wreak havoc on the natural intestinal microbiota of patients and allow several potentially harmful bacterial strains to proliferate. In particular, the bacterium Clostridium difficile proliferates and can cause potentially life-threatening infections. DAV132 is co-administered with antibiotics and functions as a non-specific adsorbent that can capture antibiotics in the lower intestinal tract before they can signficantly alter the patient’s microbiota. However, DAV132 is said to be inactive in the upper intestinal tract and does not interfere with the drug’s therapeutic efficacy. The function of DAV132 is demonstrated in the video below.
DAV132 was co-administered with moxifloxacin in a randomized controlled clinical trial performed in 44 healthy human volunteers. According to DaVolterra, Phase I study results show that DAV132 reduced the exposure of intestiinal microbiota by 99% and maintained 97.8% of the microbiome’s genetic richness while protecting 93% of bacterial species. This sharply contrasts to a gene richness of 54% and 39% of bacterial species protected when moxifloxacin was administered alone. Dr. Jean de Gunzburg of De Volterra commented on the results of the study in a recent publication of the Journal of Infectious Diseases:
DAV132 was highly effective to protect the gut microbiome of moxafloxacin-treated healthy volunteers and may constitute a clinical breakthrough by preventing adverse health consequences of a wide range of antibiotic treatments.
Akili Interactive recently announced results of a trial on the company’s digital medicine product, AKL-T01. According to FierceBiotech, Akili plans to file AKL-T01 with the U.S. Food and Drug Administration (FDA) for clearance under the 510(k) medical device pathway as a novel treatment for children and adolescents with attention deficit/hyperactivity disorder (ADHD).
According to the article, unlike traditional drug treatments for ADHD, AKL-T01, also known as Project: EVO, is a video game patients play on a tablet device. AKL-T01 uses storytelling and reward
mechanisms, like those found in standard video games, and further uses adaptive algorithms to automatically adjust the level of stimulus up or down to target deficient cognitive neural systems in the brain and meet the specific needs of the patient.
The article further notes that in the randomized, controlled trial, 348 children and adolescents diagnosed with ADHD were evaluated before and after four weeks of at-home treatment with either AKL-T01 or an active control. According to Akili’s press release, children and adolescents who used AKL-T01 showed a statistically significant improvement in attentional functional compared to the children in the active control group. According to Akili, a full analysis of the results is underway and will be presented in upcoming peer-reviewed publications, scientific conferences, and medical meetings.
The use of interactive software as digital treatment is a relatively new trend. The FDA recently approved what it characterized as its first-ever mobile medical application, an application developed by Pear Therapeutics to treat substance use disorders. As reported by Reuters, Akili’s plan to file for FDA approval may pave the way for what would be the first such digital prescription product to tackle ADHD. Considering that Pear Therapeutics was recently selected to participate in the FDA’s digital health software precertification pilot program, the FDA has provided an indication that the agency may be interested in the type of digital therapy treatment Akili claims to offer.
The FDA recently issued a draft guidance document intended to “to ensure that least burdensome principles are implemented for all device-related applications and interactions with FDA.” The FDA provides this draft guidance following a December 2017 Government Accountability Office (GAO) report assessing the FDA’s application of the “least burdensome” approach to regulation.
The least burdensome mandate for medical devices has been a part of the FDA’s governing law since Congress’ passage of the FDA Modernization Act of 1997. Its intent is to eliminate unnecessary delays for approving new devices, while still maintaining the statutory requirements for approval. The GAO report found that, between 2013 and 2016, device sponsors had appealed FDA staff decisions to agency management a total of 63 times. Of these 63 appeals, 33 raised issues related to the FDA’s application of the least burdensome approach, and the FDA at least partially agreed in 11 of these cases. The GAO report further notes that the FDA has not evaluated its compliance with the least burdensome mandate and suggests the development of performance metrics to meet this end.
FDA Commissioner Scott Gottlieb states that he is “fully committed” to implementing the least burdensome mandate. The draft guidance defines least burdensome to be the “minimum amount of information necessary to adequately address a regulatory question or issue through the most efficient manner at the right time.” The guiding principles espoused in the draft guidance include the FDA’s intent to require the “minimum information necessary to adequately address the regulatory question or issue at hand,” a call for industry sponsors to submit “well-organized, clear, and concise information” for the FDA to review, and the FDA’s commitment to apply regulatory approaches that “fit the technology, taking into account its unique innovation cycles, evidence generation needs, and timely patient access.”
The draft guidance also provides examples of how the least burdensome approach can be applied. For example, it suggests that:
- Computer modeling and simulations “should be used to support medical device safety and effectiveness as alternatives to traditional benchtop or animal performance testing in appropriate circumstances.”
- “Alternative approaches should be considered, when appropriate, to optimize the time and resources of FDA and industry. Both FDA and industry should understand that there are often
multiple ways to satisfactorily address a particular regulatory issue. The resolution of the regulatory issue should be based on a discussion about which method is least burdensome, while still satisfactorily addressing the regulatory issue.”
- “Bench performance testing should be considered to address preclinical or clinical endpoints,
when appropriate. This may include bench models for anatomy, such as evaluating tortuous
paths for catheters used across many clinical applications.”