Medtronic Gets FDA Approval for Less-Invasive Heart Pump Implant Procedure

Medtronic plc (NYSE: MDT) has received United States
Food and Drug Administration (FDA) approval for a less-invasive implant approach
of its HVAD(TM) System, a left ventricular assist device (LVAD) for patients
with advanced heart failure. The HVAD System is the smallest commercially
available LVAD, and the only LVAD approved in the U.S. for implant via
thoracotomy, a small lateral, surgical incision between the patient’s ribs on
the left side of the chest.

LVADs help the heart pump and increase the amount of blood that flows through
the body. They are typically implanted via median sternotomy, a surgical
procedure in which a vertical incision is made down the middle of the chest,
after which the sternum (or breastbone) is divided.

FDA approval for HVAD implantation via thoracotomy is based on data from the
LATERAL prospective clinical trial, in which 144 patients, with end-stage heart
failure who were eligible for heart transplant, were enrolled at 26 centers in
the U.S. and Canada. The primary endpoint of the trial demonstrated non-
inferiority of the HVAD implanted in patients via thoracotomy, where survival at
six months free from disabling stroke or device explant or exchange due to
malfunction was achieved in 88.1 percent of patients. Since the success outcome
exceeded the pre-specified performance goal of 77.5 percent, the trial achieved
its primary endpoint (p=0.0012). The key secondary endpoint revealed a
significant reduction in total length of hospital stay, from an average of 26.1
days down to 18 days (p<0.001). Overall survival among patients receiving an
HVAD via the thoracotomy procedure was 88.8 percent at one year. Detailed
outcomes of the LATERAL trial and its secondary endpoints were presented at The
International Society for Heart and Lung Transplantation (ISHLT) 2018 Scientific
Sessions.

“We have demonstrated that a thoracotomy is a safe and effective implant
technique for the HVAD System, which gives physicians added flexibility in
treating a broad range of patients,” said Edwin McGee, Jr., M.D., professor and
director, Heart Transplant & Ventricular Assist Device Program, Loyola
University Medical Center, Maywood, Ill., and principal investigator of the
LATERAL trial. “Implanting the HVAD via thoracotomy preserves the chest for a
subsequent procedure that patients may need, such as a heart transplant. It also
has been shown to result in shorter hospital stays.”

The HVAD System is the only LVAD approved in the U.S. and Europe for implant via
a thoracotomy as well as a median sternotomy. It is approved to treat patients
with advanced, refractory heart failure as a bridge to cardiac transplantation
and as destination therapy in patients for whom subsequent transplantation is
not planned.

In addition to this approval, new surgical implant tools tailored to assist
physicians with the thoracotomy approach for the HVAD System are now available
in the U.S. and in CE Marked countries.

“The thoracotomy approach showed significant improvements in patients’ quality
of life and functional capacity, supported by strong safety and effectiveness
data from the study,” said David Steinhaus, M.D., vice president and general
manager of the Heart Failure business, which is part of the Cardiac and Vascular
Group at Medtronic. “Further, the added flexibility for implant approach offers
a unique advantage of the HVAD System.”

The Medtronic portfolio of therapies, diagnostic tools and services for patients
suffering from heart failure includes CRT devices, including MR-conditional CRT-
Ds and CRT-Ps; mechanical circulatory support therapy for advanced heart failure
patients; heart failure diagnostics; and meaningful expert analysis through
Medtronic Care Management Services.

In collaboration with leading clinicians, researchers and scientists worldwide,
Medtronic offers the broadest range of innovative medical technology for the
interventional and surgical treatment of cardiovascular disease and cardiac
arrhythmias. The company strives to offer products and services of the highest
quality that deliver clinical and economic value to healthcare consumers and
providers around the world.

https://bit.ly/2um4Soo

Nevro may prevail in court against Boston Scientific: JMP

JMP Securities analsyt David Turkaly reiterated his Market Outperform rating and $105 price target on Nevro Corp (NYSE: NVRO) following daTuesday’s tentative ruling in the NVRO/BSX patent case.

Turkaly said while they are not legal experts, some of the language appears to question the validity of some of NVRO’s intellectual property being considered in the case.

“Specifically, it appears that the Court has pointed out potential issues with nonparesthesia producing language and with software and/or the programming aspect being the inventive concept,” he notes.

The analyst reiterated that this is not a final judgement and notes both companies have until July 11th to file post-hearing briefs. They note NVRO has been successful in defending its IP in the past (including in 2015 when the BTAP did not institute an inter partes review for any of the BSX challenged claims).

“Subject to further information and due diligence, we remain at a Market Outperform rating,” he concluded.

https://bit.ly/2ueJxhn

Patients Aren’t Shopping Around for Healthcare, but ‘Experts’ Are No Help

The whole idea of giving patients financial “skin in the game” so they’ll be motivated to shop around and lower their healthcare costs hasn’t been working and needs to be rethought, several experts said here.

“Maybe we need to rethink the value of the high-deductible health savings account,” Tara O’Neill Hayes, deputy director of healthcare policy at the American Action Forum, a right-leaning think tank, said here Tuesday at an event sponsored by the National Coalition on Health Care. “Maybe we put a little too much in that basket.”

Paul Ginsburg, PhD, director of the USC-Brookings Schaeffer Initiative for Health Policy at the Brookings Institution, a left-leaning think tank, agreed. He noted that when it comes to the idea of having consumers shop around to get cheaper care, “[Our] experience [with] providing good pricing [data] to consumers is not encouraging at all; they don’t go there. They don’t use it … Just having consumers be in high-deductible health plans and giving them price information is not the most effective way to get them to be better consumers.”

What would work better, Ginsburg said, is capping the amount of money for health insurance premiums that workers could exclude from their taxable income. That would force people to buy less expensive health plans from their employers “without all the bells and whistles,” he told MedPage Today.

At the event, the coalition presented its report on strategies for improving healthcare affordability. The report identified six drivers of healthcare costs:

• Chronic illness rooted in non-medical determinants of health
• Poorly coordinated, inefficient care delivery
• Misuse of provider market power, caused in part by providers who demand guaranteed inclusion in contracts
• Barriers to drug price transparency and competition
• Insurance and reimbursement rules that promote cherry-picking of healthier patient populations
• Cost barriers to high-value care, such as increasing deductibles

When it comes to that last item — barriers to high-value care — John Rother, the coalition’s president and CEO, pointed out that “not all healthcare has the same value. Certain procedures and interventions offer high value and there are others that offer low value, and yet we don’t distinguish [between them] and people with coverage often don’t understand the difference. By removing barriers to higher-value care, we could definitely make a positive impact on healthcare.”

The coalition offered several suggestions for improving affordability:

• Focus on the non-medical determinants of health. This would probably offer the best value, said Rother. “Investments in children in particular have a long-term payoff. There’s no question that dollar for dollar, investments in child health through Medicaid and through [the Children’s Health Insurance Plan] is the single best investment we can make”
• Make healthcare more efficient by promoting value-based care. “We need to build the infrastructure [for that], including more emphasis on primary care and a common set of performance measures that tell us how we’re doing and where investments have the best payoff,” he said
• Curb misuse of the market power of providers. “There is tremendous consolidation in healthcare going on today as providers look to enhance their own market power,” and fixing the problem will require leadership from the Federal Trade Commission as well as state lawmakers, Rother said
• Eliminate barriers to transparency and competition in drug pricing. “Drug pricing has gotten a lot of attention lately and I think deservedly so,” he said. “We’re seeing the price increases for brand-name drugs overwhelm the savings we get from generics, and it’s likely to increase in the future as more and more new drugs are very expensive biologics that run six figures a year.” Promoting more competition among drugmakers and a better pathway for biosimilars would help, as would broader formularies and a greater ability for Medicare to negotiate prices based on comparative effectiveness, Rother added
• Promote increased use of high-value healthcare. “We could exclude primary care from deductibles, and also exclude chronic care services. We need to think about what works and measure it, and perhaps implement it more broadly”

Gerard Anderson, PhD, of Johns Hopkins University in Baltimore, gave a historical perspective on the issue; he noted that in 2003, he and several colleagues, including the late Princeton University health economist Uwe Reinhardt, PhD, wrote a paper entitled, “It’s the Prices, Stupid,” which explained that the reason for the high cost of healthcare was payers’ willingness to put up with high prices.

“We were looking at the reason for these higher costs — we looked at defensive medicine, higher educational costs for physicians, the aging of the population, the administrative burden, and [the fact that] Americans were sicker,” said Anderson. “But [for each one] we said, ‘Yeah, that’s not the real reason’ … We found that it was the prices.”

Some of the researchers involved have redone their analysis “and most everything remained exactly the same in the last 15 years,” he continued. There was one difference: when the group wrote its original paper in 2003, the private sector and the public sector were paying about the same rate for healthcare, but now the private sector is paying much more.

“You can talk about cost-shifting, but for me, one of the main reasons for growth in last 15 years … is the willingness of the private sector to continue to pay ever-increasing prices for goods and services,” said Anderson. “The question is, can we mobilize them … or do we have to give them some government help?

https://bit.ly/2zunyZ3

Otsuka jumps into the US biotech M&A game, bagging Visterra in $430M buyout

After raising a bit more than $117 million from some blue chip backers like the Bill & Melinda Gates Foundation, Vertex and Flagship, Waltham, MA-based Visterra has agreed to a $430 million buyout deal, joining Japan’s Otsuka as a subsidiary.

Visterra and its antibody platform — all about binding to epitopes — will now remain in operation under Otsuka, which joins a growing group of Japanese companies with a big presence in the Boston hub.

Just last fall Visterra CEO Brian Pereira topped up their C round and closed it with $46.7 million in venture cash — enough to steer their lead program through a Phase IIb while getting another therapy through Phase I. And right after the latest venture round, George Scangos’ new infectious disease startup Vir stepped up with a $1 billion-plus development deal for up to 5 new drugs.

The lead program is for VIS410, designed to fight influenza A in a way that centers on epitopes common across all strains of a virus. Targeting that immutable spot on the ever-changing flu virus with tech insights out of the lab of MIT’s Ram Sasisekharan could lead to a durable remedy for large numbers of patients.

Their C round last fall came after a failed attempt at an IPO, which was dropped well before the big wave of new offerings that hit earlier this year.

Otsuka President Tatsuo Higuchi noted:

I am highly gratified that Visterra’s exceptional antibody platform technology, promising pipeline and talented researchers will join up with Otsuka.

https://bit.ly/2mbAsBm

resTORbio Positive Phase 2a Data for Seniors Immunity, Lower Infection Rates

resTORbio (Nasdaq: TORC) today announced newly published data from a Phase 2a clinical trial demonstrating that target of rapamycin complex 1 (TORC1) inhibitor treatment improved immune function and decreased incidence of all infections, including respiratory tract infections (RTIs), in people aged 65 years and older. RTIs in particular are a significant health risk for the elderly with life-threatening consequences and few treatment options. Data were published in the July 11, 2018 online edition of the journal Science Translational Medicine.

“Inhibition of TORC1 has extended both lifespan and healthspan in multiple pre-clinical species,” said Joan Mannick, M.D., Co-Founder and Chief Medical Officer of resTORbio. “The results of this Phase 2a trial raise the possibility that TORC1 inhibition also has health benefits in older humans. In the Phase 2a trial, TORC1 inhibitor treatment was associated with a clinically meaningful reduction in the incidence of infections in people aged 65 years and older and an enhancement in the function of the aging immune system as assessed by influenza vaccination response and antiviral gene expression. The results need to be validated in additional clinical trials, but may have broad implications for the treatment of diseases of aging that we are actively investigating with our TORC1 inhibitor program.”

The data for this publication were gathered in a randomized, double-blinded, placebo-controlled Phase 2a study of 264 elderly volunteers at least 65 years of age without unstable medical conditions. Subjects were treated for 6 weeks with study drug and after a 2-week drug-free interval, were given a seasonal influenza vaccine. The incidence of infections was assessed for one year after initiation of study drug treatment. In the RTB101 monotherapy and RTB101+everolimus combination treatment arms, statistically significant and clinically meaningful reductions in the annual rate of infections of 33% (p=0.008) and 38% (p=0.001), respectively, compared to placebo, were observed. In addition, both RTB101 monotherapy and the RTB101+everolimus combination therapy were observed to reduce the incidence of RTIs at one year by 42% (p=0.006) and 36% (p=0.01), respectively. The combination of RTB101+everolimus was also observed to significantly enhance the response to influenza vaccination and upregulated the expression of critical antiviral genes that play a key role in enabling the immune system to protect the elderly from respiratory tract infections.

RTIs are the fourth leading cause of hospitalizations and the seventh leading cause of death in people aged 65 years and older in the United States. Moreover, the majority of RTIs in the elderly are caused by viruses for which there are currently no approved therapies. resTORbio’s TORC1 inhibitor program has the potential, if successfully developed and approved, to be a new class of immunotherapy that enhances the function of the aging immune system to fight infectious pathogens including viruses, and thereby reduce the incidence of respiratory tract infections.
Based on the results of the Phase 2a study, resTORbio is conducting a Phase 2b clinical trial to further investigate the potential benefits of RTB101 alone and in combination with everolimus in aging-related diseases. In the ongoing Phase 2b study, doses of RTB101 alone and in combination with everolimus are being evaluated as an immunotherapy to decrease the incidence of RTIs in older people at increased risk of morbidity and mortality from RTIs (defined as age 85 and older and age 65 and older with comorbidities). Dosing has been completed in the Phase 2b study and 16-week topline data are expected to be reported in the third quarter of 2018.

https://bit.ly/2Lag7aH

Novartis hands off cancer med to China’s Adlai Noryte

Adlai Noryte grabbed worldwide rights to Novartis’ buparlisib, an oral PI3K inhibitor being developed for blood cancers and solid tumors that has run into toxicity issues.

Except for “certain rights” maintained by Novartis, Adlai Noryte has exclusive development and commercialization rights to buparlisib for therapeutic, prophylactic and/or diagnostic use in humans, the company said in a statement.

“Buparlisib has been extensively profiled in breast cancer and other tumor types. Buparlisib when combined with other therapies has shown impressive anti-cancer efficacy in [head and neck squamous cell carcinoma],” said Adlai Noryte CEO Carsten Lu in the statement. “It has very good market prospects when combined with paclitaxel, and we are planning to carry out clinical trials of combination of buparlisib and immune check point inhibitor treatment.”

While Adlai Noryte is painting a rosy picture for buparlisib, a paper published last December in The Lancet Oncology “does not support” its further development. The study tested buparlisib in combination with fulvestrant in patients with HR-positive, HER2-negative breast cancer that progressed even after treatment with endocrine therapy and mTOR inhibitors.

This safety profile is unsurprising in a field dogged with safety issues. Gilead’s Zydelig, approved in 2017 for three types of blood cancers, is indicated for use in combination with Rituxan, or in patients who have already failed two other therapies. Safety issues hamstrung Gilead’s efforts to get the drug approved as a first-line therapy.

While the median progression-free survival in the buparlisib arm was “significantly longer” than in the group that received placebo, about one-fifth of the buparlisib patients experienced serious adverse events, including aspartate aminotransferase, dyspnoea and pleural effusion. Of the grade 3-4 adverse events observed, the most common were elevated alanine aminotransferase (22% versus 3% in the placebo group) and elevated aspartate aminotransferase (18% versus 3%).

The treatment group also experienced higher rates of hypertension and fatigue than the control group did, but these rates were closer together—6% versus 4% and 3% versus 1%, respectively.

While the safety profile is troubling, the study authors did say that buparlisib’s efficacy suggests that PI3K inhibitors might be effective alongside endocrine therapy in patients with PIK3CA mutations.

Novartis isn’t the only company to hand off the rights to a PI3K inhibitor. Roche out-licensed its PI3K drug to Australia’s Novogen in 2016 and Eli Lilly started seeking partners in July 2017 for several midphase oncology programs, including a PI3K/mTOR dual inhibitor. And it didn’t stop there—just last month, Roche ditched its PI3K hopeful, taselisib, after it put up “modest” efficacy data and a risk of “considerable side effects.”

The news comes a week after Adlai Noryte raised $53 million in its series B. The Hangzhou, China-based biotech’s lead asset is an oncolytic virus dubbed Reolysin, which is poised to enter phase 3 in breast cancer. It is also working on an oral EP4 antagonist for solid tumors and an IDO inhibitor for “various tumor types.”

https://bit.ly/2KXsYjN

Pharmas call off price hikes after California law forces new warnings

With a new law requiring drugmakers to provide notice about certain price hikes, California last year joined the group of states taking their own action on drug prices. Now, several pharma companies have canceled previously planned increases after the changes took effect, Bloomberg reports.

Novo Nordisk, Roche, Novartis and Gilead have notified California health plans that they’re canceling or reducing previously disclosed price increases, according to the news service. The report is based off an anonymous health plan official, but Novo Nordisk, Roche and Novartis confirmed their decisions in statements to Bloomberg. Bloomberg reports that Gilead didn’t respond to its requests for comment.

In a statement to FiercePharma, a Novartis representative said “many factors influence our decisions to change product prices for our U.S. portfolio and it is not uncommon for us to adjust plans for price changes.”

After filing a notice of increases on a California government website, he said Novartis “made the business decision not to take planned price increases.” The drugmaker “provided an updated notification explaining that we will not implement the changes.”

A Novo Nordisk spokesman told FiercePharma the company has reduced a planned increase. Roche didn’t immediately respond to a request for comment. Gilead declined to comment.

Together, the four companies canceled or reduced planned hikes on at least 10 meds, according to Bloomberg, including Novartis’ Cosentyx and Gilead’s Latairis.

The news comes at a tense time for pharma on pricing, a factor that also might have played a role in the decisions. This week, industry giant Pfizer backtracked on dozens of July price hikes after President Donald Trump highlighted the increases on Twitter and said the company “should be ashamed” of its move. Trump spoke with Pfizer CEO Ian Read and the company agreed to defer the hikes, according to a Pfizer statement.

California’s new drug pricing law requires drug companies to provide a 60-day notice of planned increases that would take a med’s list price up 16% when combined with increases from the previous two years. It also forces companies to justify such price hikes.

After Gov. Jerry Brown signed the legislation into law, Leerink Partners Geoffrey Porges wrote that the law could create a new de facto price hike limit of 5% in pharma. Alternatively, he said, it could trigger bigger hikes because if companies hit the 16% price hike threshold, they might be incentivized to go “well above” that number.

Still, one expert told Bloomberg the companies could be “throwing up a smokescreen” with their decisions to reduce or cancel price increases. According to SSR analyst Richard Evans, the companies could be seeking to shield details about actual price hikes from competitors or purchasers.

Meanwhile, industry trade group PhRMA is challenging the California law. The group filed a lawsuit last year arguing the law is “poorly conceived,” “counterproductive” and “unconstitutional.” PhRMA said the law “intentionally exports California’s policy choices regarding prescription drug pricing on the entire nation.”

California officials declined to comment on the lawsuit. The state is among a number that have taken action on pricing in recent years, including Nevada, Oregon and an attempt in Maryland. Maryland officials tried to crack down on “unconscionable” price hikes in the generic sector, but an appeals court later struck down the state’s law because it regulates transactions that occur outside of Maryland’s borders.

https://bit.ly/2KYrLZv