FDA kills off Amicus’ 2018 accelerated approval plan

The FDA has told Amicus Therapeutics it cannot file for accelerated approval of Pompe disease drug AT-GAA using its existing data. Amicus must now continue adding to its existing phase 1/2 data with a view to sitting down again with the agency next year.

Going into 2018, Amicus harbored hopes that the dire need for new treatments for people with the inherited lysosomal storage disorder Pompe would persuade regulators to wave through AT-GAA on the strength of early-phase data. Those hopes took a big blow in June when the EMA told Amicus it lacked the data for conditional approval in Europe.

Now, the FDA has killed off talk of an application for accelerated approval on the basis of existing data, pushing back a filing until 2019 at the earliest. Amicus is set to meet with the EMA and FDA next year to present its expanded dataset.

Amicus’ plans to resume talks about quickie approvals on both sides of the Atlantic rest on three upcoming data drops. This year, Amicus expects to have 18-month data on 19 participants in its phase 1/2 trial and a readout from its 100-person retrospective natural history study. The final piece will fall into place next year when Amicus shares a look at the progress of 10 patients it enrolled in a later cohort of the phase 1/2 trial.

Work toward an accelerated approval is advancing in parallel to efforts to generate pivotal data on Amicus’ recombinant human acid alpha-glucosidase. Having spoken to the EMA and FDA, Amicus plans to start a single pivotal trial in 100 Pompe patients by the end of the year. The trial will be open to people who have previously received enzyme replacement therapy and treatment-naïve patients alike.

Amicus will accept patients enrolled in its natural history study into the pivotal program, giving it a readymade pool of people to recruit for the upcoming trial. Participants in the trial will perform the six-minute walk test after 12 months of treatment to generate data on the primary endpoint.

https://www.fiercebiotech.com/biotech/fda-kills-off-amicus-2018-accelerated-approval-plan

Takeda family calls out CEO Weber over Shire deal

Takeda’s Shire buyout has driven a wedge between the deal’s mastermind, CEO Christophe Weber, and the founding Takeda family, as a senior member of the family has publicly voiced his opposition to the $62 billion deal.

Kazu Takeda, a descendant of the company’s founder, sided with a small group of opponents and said the takeover would be “disastrous” for the business. The opponents claim it would hurt the company’s philosophy of “Takeda-ism,” which entails making people happy as a key for driving profit.

“We understand that scaling up is necessary, but Takeda management has to think about the traditional corporate culture and the health of the company,” said Takeda, as quoted by The Times. “Hasty decisions on big deals should be avoided. It will lead to disaster if there are large-scale mergers and acquisitions without careful consideration.”

There it is, out on the table, the clash between a traditionalist and a Western executive aiming to bring a 237-year-old Japanese pharma giant to the global stage. Now rallied under the campaign Thinking about Takeda’s Bright Future, the family members and other shareholders have criticized the drugmaker for taking on too much debt—a $30.85 billion bridge loan to be precise—to help fund the gigantic deal that’s slated to become Japan’s biggest outbound takeover.

Weber and his management team, however, have touted it as an opportunity to build up Takeda’s leading positions in rare diseases, gastroenterology, neuroscience and oncology. Besides, Shire’s robust pipeline could also fill the near- and mid-term revenue gap at Takeda, which currently lacks late-stage assets.

A wider global footprint is also what Weber is eyeing. Japan currently still accounts for about a third of the company’s total revenue, though the market has seen sharp declines amid pricing pressure and competition. For the fiscal year ended in March, Takeda’s revenue in its home country dropped 11.4% to 580.3 billion Japanese yen ($5.2 billion). The addition of Shire will tip the balance more toward the U.S. and Europe.

Despite low support for the dissidents, the deal did raise some eyebrows when it was first rumored in March, but since then Weber has stressed the company’s cost-cutting plan that aims to reduce debt to two times EBITDA in a few years. It includes saving $1.4 billion in three years after closing and cutting up to 7% of the combined workforce.

The dissidents previously sought to thwart Weber by proposing to require shareholder approval in advance for large acquisitions like Shire. But they failed to move the needle at a shareholder meeting in June with only about 10% backing.

Next up, they hope to win at least a third of shareholder votes to quash Takeda’s proposal to issue new shares as a financing measure. They had argued the issuance “might significantly dilute the earnings per share, which is a dividend resource, and there is a danger of causing a great disadvantage to existing shareholders including institutional investors.” To do that, they’re reportedly looking for support from retail customers in Japan, which hold about 25% of shares.

https://www.fiercepharma.com/pharma/takeda-founder-family-alarms-ceo-christophe-weber-disastrous-shire-buyout-deal

Gene-editing patent challenge rejected by Federal Circuit appeals court

The U.S. Court of Appeals for the Federal Circuit has ruled that Harvard-affiliated Broad Institute can keep its patents on gene-editing technology CRISPR. The court rejected the argument that the work was already covered by patents owned by the University of California at Berkeley. Companies developing CRISPR-based therapies include Editas Medicine (EDIT), Intellia Therapeutics (NTLA), and Crispr Therapeutics (CRSP).

https://thefly.com/landingPageNews.php?id=2788023

Sorrento Therapeutics raises $140M in royalty-based financing

Sorrento Therapeutics (NASDAQ:SRNE) announces that its majority-owned subsidiary, Scilex Pharmaceuticals, closed a debt financing with leading global institutional investors for gross proceeds to Scilex of $140M.

Net proceeds will be used for working capital and general corporate purposes in respect of commercialization of ZTlido (lidocaine topical system) 1.8%.

On September 7, Scilex issued and sold senior secured notes due 2026 in an aggregate principal amount of $224M for an aggregate purchase price of $140M. The holders of the Notes will be entitled to receive quarterly payments of principal of the Notes equal to a percentage of the net sales of ZTlido.

ZTlido is indicated for the relief of pain associated with post-herpetic neuralgia, also referred to as post-shingles pain.

Additionally, Scilex has recruited a team of 11 regional business directors and has partnered with Syneos Health (formerly InVentiv Health) to support a sales force of over 100 representatives.

https://seekingalpha.com/news/3388933-sorrento-therapeutics-raises-140m-royalty-based-financing-support-commercialization-ztlido

ProQR childhood blindness drug succeeds in early trial

Shares of ProQR Therapeutics NV surged 70 percent in premarket trading on Tuesday after an interim analysis of an early-stage trial showed that its experimental treatment for a rare form of childhood blindness improved vision.

The Dutch drug developer said it would now stop enrollments for the small study and progress to a mid-stage trial, which is expected to start in the first half of 2019.

The trial tested ProQR’s RNA-based drug, QR-110, in 10 patients with a certain genetic mutation that causes an eye disorder called Leber’s congenital amaurosis 10.

There are no approved treatments for the condition that primarily affects the retina and leads to severe visual impairment, beginning in infancy.

There are at least 2,000 patients in Europe and the United States with the specific mutation, according to the company’s estimates.

After three months of treatment, about 60 percent of subjects showed a clinically meaningful response with improvements in vision and the ability to navigate, ProQR said.

The data show a “rapid and sustained benefit on every metric of vision assessed,” JMP Securities analyst Liisa Bayko said.

Bayko said the market is worth over $700 million and the only other potential competitor is the gene-editing treatment approach from Editas Medicine Inc.

She said QR-110 now has a 60 percent probability of success, a huge jump from her previous estimate of 20 percent, and notes that the drug is likely to be launched in the United States in 2021, a year earlier than previously estimated.

“These results are very encouraging for our broader pipeline,” Chief Executive Officer Daniel de Boer told Reuters, adding that the company was testing other drugs with similar mechanism.

ProQR is developing treatments for other rare eye diseases, including Usher syndrome and Stargardt’s disease.

De Boer said the company was not planning to seek partners to develop the drug, QR-110.

ProQR is separately testing treatments for lung disease cystic fibrosis and skin disorder dystrophic epidermolysis bullosa.

The company’s shares were trading at $13.50, on track to open at a near three-year high. Shares have more than doubled since the beginning of the year.

https://www.reuters.com/article/us-proqr-study/proqr-drug-for-rare-childhood-blindness-succeeds-in-early-trial-idUSKCN1LL0RN

Hanger, AT&T in industry-1st, network-linked device for prosthetic limbs

Along with AT&T*, Hanger, Inc. (OTC PINK: HNGR) today announced the two companies have developed a trailblazing proof of concept for the industry’s first standalone, network-connected device for prosthetic limbs. The prototype, designed to attach to below-the-knee prostheses, is simple and highly mobile as it syncs directly to the cloud via AT&T’s network without relying on Wi-Fi, Bluetooth, or a separate mobile device. This connectivity allows Hanger Clinic, the patient care subsidiary of Hanger, to receive data on patients’ prosthetic usage beyond the clinical setting. Equipped with these insights, Hanger Clinic clinicians can proactively contact patients to address potential issues impacting prosthesis usage, such as fit and comfort, to in turn increase mobility.

Physical mobility is intrinsic to our everyday lives – running, bathing, dressing, driving. Now imagine losing a limb. When professional acrobat Andrew ‘AJ’ Montgomery underwent a below-the-knee amputation following a motorcycle accident three years ago, he didn’t just have to re-learn once-instinctual movements. He also faced the uncertainty of continuing his acrobatic career with a prosthesis.

‘After my amputation, I wasn’t sure how to tackle my life – where I’d left off, where I’d be going,’ Montgomery said.

Those experiencing limb loss face an unfamiliar journey to finding their way to restored mobility. Some who don’t know where to begin might not communicate their challenges with their prosthetic clinicians, potentially leading to lack of use of their prosthesis.

But what if the prosthesis could talk directly to the patients’ caregivers? If this data feed could be relevant, automated and more detailed, caregivers could provide patients with better, targeted assistance. The AT&T Foundry, which is designed for collaborative innovation projects just like this, was the ideal venue for this venture with Hanger. The resulting prototype is designed to collect data on prosthetic usage and mobility in near-real time. The device is connected via AT&T’s LTE-M cellular network, and has an accompanying interactive mobile app.

‘Becoming an amputee can be an emotional, traumatic experience,’ said Aaron Flores, PhD, Hanger Clinic Vice President, who is responsible for the company’s fabrication network. ‘Transitioning from living with a fully functioning leg to a prosthesis requires re-learning how to walk entirely. Unfortunately, not everyone knows when or how to talk to us about potential challenges. This device will give us a window into patients’ daily experiences and equip us with a level of connectivity we’ve never had before, and in turn, provide even better patient care.’

Getting to an intuitive, seamless prototype required a flexible and nimble design process, collaboration and rapid iterations, which is how the AT&T Foundry approaches all its projects. In this case, combining an accelerometer, gyroscope, magnetometer and an LTE-M modem into a compact device resulted in multiple test versions of the prototype. With each version we provided new information – where to install the different components, how to balance the weight to make the prosthetic device comfortable with the prototype, the best way to capture and transmit data about speed of motion, impact force, direction, rotation, and more. In the span of just a few months, we’d gone from a concept to a prototype that was ready for real-world testing.

To put this data into action, we also prototyped an iOS app equipped with patient and clinician portals. The app will allow patients to view their day-to-day progress, such as number of steps taken. It also includes a video calling feature so patients can talk with Hanger Clinic providers about potential issues with their device. Likewise, clinicians can view their patients’ activity levels and contact those whose user data shows low activity or irregularities.

‘Because this device is intended to become a physical part of Hanger’s patients, the technology driving it needed to be intuitive and seamless while providing benefits to both the patient and the caregiver,’ said Vishy Gopalakrishnan, vice president of AT&T Ecosystem & Innovation. ‘The AT&T Foundry is uniquely suited to help customers like Hanger quickly solve these types of challenges. Through close customer collaboration, a proven ability to rapidly prototype the test solutions, and our advanced knowledge of connectivity, we’re able to move these revolutionary concepts to market faster than once possible.’

Hanger is currently trialing five of these devices with existing patients. In the coming months, Hanger and AT&T will continue to take the best components of this proof of concept to create a fully functional product for the next phase of this project.

‘At Hanger, we know to best meet our patients’ needs, we need to be the most digitally connected company in O&P, so we can connect with our patients wherever they may be,’ said Vinit Asar, Hanger President and Chief Executive Officer. ‘Collaborating with AT&T on this prototype not only allows us to equip our patients with the tools they need to get their lives back on track faster, but also helps us solidify our life-long commitment to them.’

https://www.marketscreener.com/HANGER-INC-26420594/news/Hanger-and-AT-T-create-industry-first-network-connected-device-for-prosthetic-limbs-27238025/

ACADIA Studies Evaluating Treatment in Alzheimer’s, Parkinson’s Published

ACADIA Pharmaceuticals Inc. (NASDAQ: ACAD) announced today publication of additional data from a Phase 2 single center, double-blind, placebo-controlled study to examine the safety and efficacy of pimavanserin for the treatment of psychosis in Alzheimer’s Disease Psychosis in The Journal of Prevention of Alzheimer’s Disease (JPAD). These results further demonstrate that pimavanserin may have the potential to treat dementia-related psychosis, a condition which can be present in neurodegenerative diseases such as Alzheimer’s disease, dementia with Lewy Bodies, dementia associated with Parkinson’s disease, vascular dementia and frontotemporal dementia-spectrum disorders.

The publication (https://link.springer.com/article/10.14283/jpad.2018.30) focused on the pre-specified analysis in the subgroup of patients who had more pronounced psychotic symptoms at baseline. In this subgroup of patients with more severe delusions and hallucinations, at the primary efficacy endpoint, pimavanserin demonstrated significant improvement relative to placebo with a similar and acceptable tolerability profile. These results were also presented recently at the Alzheimer’s Association International Conference in Chicago in July 2018. The primary results from the study were previously reported at the Clinical Trials in Alzheimer’s Disease (CTAD) conference in Boston in October 2017 and published in the Lancet Neurology in March 2018.

“The robust efficacy of pimavanserin in patients with more severe psychotic symptoms is relevant to the therapeutic benefits of pimavanserin in a patient population with Alzheimer’s disease and psychosis,” said lead investigator Clive Ballard, MBChB, MRCPsych, Pro-Vice-Chancellor and Executive Dean, University of Exeter Medical School. “These results extend and confirm the results from the primary analysis as well as results from the subgroup analysis of patients with mild dementia in the pivotal Parkinson’s disease psychosis study with pimavanserin. These findings, coupled with the results from other studies of pimavanserin, suggest a potential role for pimavanserin in treating dementia-related psychosis in patients across a range of neuropsychiatric conditions.”

A separate review published in JPAD(https://link.springer.com/article/10.14283/jpad.2018.29) also supports the potential use of pimavanserin in other forms of neurodegenerative diseases, including dementia-related psychosis. A research group led by Jeffrey Cummings, MD, ScD, of the Cleveland Clinic Lou Ruvo Center for Brain Health, Las Vegas, NV, looked at the clinical evidence that has been gathered to date that supports the potential efficacy of pimavanserin in dementia-related psychosis. “Clinical evidence is now available that supports potential efficacy of pimavanserin in dementia-related psychosis. This includes results from a sub-analysis of mildly demented patients in the Phase 3 pivotal study in patients with Parkinson’s disease psychosis, and the Phase 2 study in patients with Alzheimer’s disease. Based on the overlap in clinical presentation and pathology and the positive clinical trial results in two neurodegenerative patient populations, we think it is important to continue to evaluate pimavanserin’s effect in patients with hallucinations and delusions across a number of neurodegenerative disorders,” said Dr. Cummings.

ACADIA is currently conducting the Phase 3 HARMONY study in dementia-related psychosis. This is a randomized withdrawal study designed to evaluate the efficacy of pimavanserin in preventing relapse of psychotic symptoms in patients with dementia-related psychosis. Patients whose dementia-related hallucinations and delusions respond to 12 weeks of open-label treatment with pimavanserin are randomized, in a double-blinded manner to continue pimavanserin therapy or to placebo. The primary endpoint of this study is the average time to relapse between pimavanserin and placebo. Studies suggest that 30% of patients with dementia have psychosis, commonly consisting of hallucinations and delusions. Serious consequences have been associated with severe or persistent psychosis in patients with dementia. These consequences can impact both patients and their families. Medications that are currently used off-label to treat dementia related psychosis have been shown to impair cognition in this already impaired population.

https://www.marketscreener.com/ACADIA-PHARMACEUTICALS-IN-8222/news/ACADIA-Pharmaceuticals-Analyses-of-Pimavanserin-Studies-Evaluating-Treatment-in-Alzheimer-rsquo-s-27237102/