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Tuesday, June 21, 2022

Enanta : Filed Patent Infringement Suit Against Pfizer Over Paxlovid

 Biotechnology company Enanta Pharmaceuticals Inc. on Tuesday said it filed a patent infringement suit against Pfizer Inc., seeking damages in the manufacture, use and sale of Paxlovid.

Enanta said it received a patent earlier this month based on a July 2020 patent application "describing coronavirus protease inhibitors invented by Enanta scientists."

Paxlovid has been used to treat patients suffering from Covid-19. Enanta said it "does not intend to seek an injunction or take other action in this litigation that would impede the production, sale or distribution of Paxlovid." The company said it "seeks fair compensation for Pfizer's use of a coronavirus 3CL protease inhibitor claimed" in its patent.

The suit was filed in the U.S. District Court for the District of Massachusetts, Enanta said.

Pfizer didn't immediately respond to a request for comment.

https://www.marketscreener.com/quote/stock/ENANTA-PHARMACEUTICALS-I-12855346/news/Enanta-Filed-Patent-Infringement-Suit-Against-Pfizer-Over-Paxlovid-40780734/

Heart Failure Drugs Can Be Unaffordable on Medicare, Study Finds

 Nearly all Medicare prescription drug plans restricted coverage of established heart failure medications to some degree, most commonly by requiring cost-sharing, according to recent data.

Tier level 3 or higher cost-sharing was required for angiotensin receptor-neprilysin inhibitor (ARNI) therapy and at least one SGLT2 inhibitor in approximately 99% of the 4,065 Medicare Advantage and standalone Part D plans active in the second quarter of 2020 that covered these medications.

The sole ARNI on the market, sacubitril/valsartan (Entresto), was subject to prior authorization as well, as stipulated by 24.3% of drug plans. Meanwhile, step therapy was required for SGLT2 inhibitors and the mineralocorticoid receptor antagonist (MRA) eplerenone (Inspra) in 5.4% and 0.8% of plans, respectively, reported Kamil Faridi, MD, MSc, of Yale School of Medicine, and colleagues in the Journal of the American College of Cardiology.

Quadruple therapy for heart failure consists of ARNI, SGLT2 inhibitors, MRAs, and beta-blockers. Faridi's group estimated that out-of-pocket costs for a 30-day standard course of quadruple therapy reached a median $94 -- mostly driven by the cost of ARNI ($47) and SGLT2 inhibitors ($45) -- a total far exceeding the $3 cost of a wholly generic drug regimen.

"Quadruple therapy may be unaffordable for many Medicare patients with HFrEF [heart failure with reduced ejection fraction] unless medication prices and cost-sharing are reduced," the authors wrote.

"For patients to take these medications and experience their therapeutic benefits, they must be able to access them through their health insurance and afford the combined OOP [out-of-pocket] costs," they said. "This is an especially important issue for older patients enrolled in Medicare, who often have fixed incomes and significant expenses related to treatment of other comorbid conditions."

In a corresponding editorial, other cardiologists complained that cost-sharing limits access to care for many patients.

"These policies likely disadvantage relatively poorer patients," wrote ​​Jason Wasfy, MD, MPhil, and Anna O'Kelly, MD, MPhil, both of Massachusetts General Hospital in Boston. "A reasonable approach to considering appropriate drug prices and coverage policies is to start by making distinctions among efficacy, effectiveness, and cost-effectiveness."

"As a general framework, cost-effectiveness analysis allows a rational basis for establishing a common ground between drug manufacturers and insurance plans," Wasfy and O'Kelly noted. "Without common ground, patients and clinicians are caught in the middle. This friction can disincentivize even cost-effective therapies and worsen disparities."

Faridi and colleagues estimated that for 50% of beneficiaries, out-of-pocket costs of quadruple therapy ate up at least 7% of their pretax income. The figure jumped to 13% when looking at those who were in the lowest quartile of income.

"Patients who do pay OOP costs for quadruple therapy may be at risk of financial toxicity, characterized by the myriad of adverse impacts of health care expenditures on patients and their families, including lower medication adherence, worse mental and physical health, delaying or foregoing medical care, and food insecurity," the authors wrote.

"Because of these findings, clinicians should assess whether OOP costs are affordable or may be leading to nonadherence among patients who are prescribed ARNI and [SGLT2 inhibitors]," they urged.

"More consensus on value-based pricing could improve access to critical therapies for patients who need them," Wasfy and O'Kelly suggested.

Study authors estimated that the majority of beneficiaries would have paid their $435 deductible by January, and the OOP costs would have been cleared once the coverage gap was reached around May. Once drug costs totaled $9,719, the beneficiaries would have moved from the coverage gap onto the catastrophic coverage phase in September.

A limitation of the study was that the authors estimated the costs of the drugs used by the participants without taking insurance plan premiums into account, nor the cost of other medications.


Disclosures

The study was funded by a grant from the NIH.

Faridi reported no conflicts of interest.

Wasfy disclosed support by the American Heart Association and the NIH, consulting fees from Pfizer, honoraria from the Institute for Clinical and Economic Review, and serving as chair of the New England Comparative Effectiveness Public Affairs Advisory Council. O'Kelly reported no conflicts of interest.

Study co-authors disclosed relationships with the NIH, Agency for Healthcare Research and Quality, Laura and John Arnold Foundation, National Evaluation System for Health Technology Coordinating Center, Greenwall Foundation, Arnold Ventures, and Johnson and Johnson.

Paratek Fast-tracked for Pulmonary Nontuberculous Mycobacterial (NTM) Disease Med

 Paratek Pharmaceuticals, Inc. (Nasdaq: PRTK) today announced the U.S. Food and Drug Administration has granted Fast Track designation for the oral and IV formulations of the company’s novel, broad-spectrum antibiotic NUZYRA® (omadacycline) for the treatment of pulmonary Nontuberculous Mycobacterial (NTM) disease caused by both Mycobacterium avium complex (MAC) and Mycobacterium abscessus (MAB). These NTM indications are rare diseases for which new therapies are desperately needed. FDA granted NUZYRA orphan drug designation for these infections in August 2021.

https://finance.yahoo.com/news/paratek-pharmaceuticals-nuzyra-receives-fda-200500754.html

IP is no barrier to COVID vaccine access, says industry

 While proponents argue waiving IP on COVID-19 vaccines would better enable low- and middle-income countries to inoculate their populations, the pharma industry has called the proposals “unnecessary and harmful to innovation”.

Proposals to waive COVID-19 product patents have been described as “political posturing” and an “answer to a problem that does not exist”.

The Quad compromise, a World Health Organization plan which would, if enacted, release members from granting or enforcing COVID-19 vaccine patents, was discussed at the 12th Ministerial Conference (MC12) last week.

But the pharmaceutical industry has said the move could “undermine innovation and industry’s ability to partner, invest at risk, and respond quickly to future pandemics”.

In a joint statement, the International Federation of Pharmaceutical Manufacturers and Association (IFPMA), the European Federation of Pharmaceutical Industries and Associations (EFPIA), the Biotechnology Innovation Organization (BIO), the International Council of Biotechnology Associations (ICBA), the Association of the British Pharmaceutical industry (ABPI), the Pharmaceutical Research and Manufacturers of America (PhRMA), and the Japan Pharmaceutical Manufacturers Association (JPMA), said: “The associations representing the global research-based biopharmaceutical industry reaffirm that weakening the IP framework, as proposed in the Quad compromise, is unnecessary and harmful to innovation.

“An IP waiver does not address inequitable access to COVID-19 vaccines and will put global health security at risk.”

Access barriers

When the COVID-19 pandemic hit, the pharmaceutical industry was quick to swing into action. The first vaccine, from Pfizer, was approved just 326 days after WHO declared the outbreak pandemic and changed the course of the global crisis.

“COVID-19 vaccines and treatments were only possible because of decades-long investment in research and an enabling IP framework that encouraged swift, voluntary partnerships across the private, public, and academic sectors.”

As of June 2022, more than 5.22 billion people, or 68% of the world’s population, had received at least one dose of a COVID-19 vaccine, and 62% were fully vaccinated. However, there is still a huge disparity in access across the globe.

In the UK, 75% of the population is fully vaccinated, a figure that stands at 67% in the United States, 79% in France, 78% in Germany, and 86% in Spain. That compares to just 0.1% in Burundi, 1.2% in Haiti, and 1.4% in Congo.

Those behind the Quad compromise believe it will allow LMIC to roll out their vaccine programmes more efficiently by allowing countries to scale up production quickly and affordably.

But the EFPIA says there is no evidence to suggest that the current IP framework has been a barrier to access. In fact, the organisation says, global vaccine production capacity is vastly exceeding demand.

“From the outset of the pandemic, industry knew that it would need to scale up quickly, seeking to build capacity before approvals were granted, partnering wherever possible, all while pledging to not compromise on quality, safety and efficacy,” said the joint statement.

By May 2021, less than six months after the first vaccine authorisation, monthly production output was close to a billion vaccine doses. This would be enough to vaccinate the world “if countries were willing and able to share,” it went on, adding that warnings about access have gone unheeded.

“Industry has called on governments to remove trade restrictions, share doses, and prepare health systems to roll out vaccinations, a message repeated in March 2022 when critical bottlenecks in vaccine delivery and administration, often linked to weak healthcare systems, were becoming even more evident.”

Since then, then IP framework has “fallen victim of political posturing”, it claims.

Accelerating roll out

The pharmaceutical industry argues the draft proposals would serve to undermine the very system that underpinned the rapid development of vaccines in the first place.

“COVID-19 vaccines and treatments were only possible because of decades-long investment in research and an enabling IP framework that encouraged swift, voluntary partnerships across the private, public, and academic sectors,” said the joint statement.

Richard Torbett, chief executive of the ABPI, says the proposals would divert attention away from supporting the efforts that are already underway to get COVID-19 vaccines to people in LMICs.

Megan Van Etten, a spokesman for PhRMA, echoed these sentiments, saying: “Efforts to waive IP commitments are unnecessary and harmful to our collective work to end the pandemic.

“Strong IP protections, voluntary technology transfers and partnerships are on target to facilitate the production of more than 20 billion doses in 2022 – more than enough to vaccinate the world – without confiscating intellectual property.”

Address the real challenges

Instead of removing IP protections, the industry believes global leaders should focus on addressing the challenges of distributing and administering vaccines to people around the world.

“We must redouble our collective efforts to achieve health equity, while ensuring health systems and delivery infrastructure are strengthened,” said the statement.

“A much better approach is to focus on the real challenges to COVID-19 vaccine access including removing trade barriers, addressing distribution challenges, strengthening healthcare systems, and partnering to drive innovation and access.”

https://pharmaphorum.com/market-access-2/ip-is-no-barrier-to-covid-vaccine-access-says-industry/

Eplontersen hits – but how hard?

 Astrazeneca and Ionis are to file eplontersen for hereditary transthyretin-mediated amyloid polyneuropathy after a planned interim analysis in the phase 3 Neuro-TTRansform trial came out positive. The antisense oligonucleotide achieved a statistically significant and clinically meaningful change from baseline in serum transthyretin concentration versus what Astra called “an external placebo group” – historical control. It also hit the trial’s other co-primary endpoint, change from baseline on mNIS+7 score, a measure of neuropathic disease progression, versus external placebo. The partners have not disclosed the extent of eplontersen’s success, but a look at the three approved therapies for this subtype of transthyretin amyloidosis shows the sort of thing doctors will be looking for. It should be noted that unlike Neuro-TTRansform, the pivotal trials of these drugs did contained placebo arms. The control in Neuro-TTRansform was in fact Ionis’s own approved Tegsedi; so far no data on this arm has been released. Stifel analysts write that the extent of the improvement on mNIS+7 is crucial, and safety, described by Astra as “favourable”, with no specific concerns, will also be important given that Tegsedi’s label has a black box warning for thrombocytopenia and glomerulonephritis. 

Cross-trial comparison of therapies for hereditary transthyretin amyloid polyneuropathy  
CompanyDrugDescriptionTrialTime pointPbo-adj chg on mNIS+7Pbo-adj chg on Norfolk QoL-DN
AlnylamOnpattroIV TTR RNAi therapeutic, given every 3wkApollo18mth-34.0-21.1
AlnylamAmvuttraSC TTR RNAi therapeutic, given every 3mthHelios-A9mth-17.0-16.2
IonisTegsediSC TTR antisense, given once weeklyUnnamed66wk (15.2mth)-19.7-11.7
Astrazeneca and Ionis EplontersenSC TTR antisense, given once monthlyNeuro-TTRansform 35wk (8mth)*HitHit
mNIS+7 = modified neuropathy impairment score +7. Norfolk QoL-DN = Norfolk quality of life questionnaire-diabetic neuropathy. *Interim data; final readout at 66wk. Source: drug labels, company releases.

https://www.evaluate.com/vantage/articles/news/trial-results-snippets/eplontersen-hits-how-hard

Exelixis Starts Phase 3 Pivotal Trial of XL092 in Metastatic Colorectal Cancer

 Exelixis, Inc. (Nasdaq: EXEL) today announced the initiation of STELLAR-303, a phase 3 pivotal trial evaluating XL092 in combination with atezolizumab versus regorafenib in patients with metastatic colorectal cancer (CRC) that is not microsatellite instability-high or mismatch repair-deficient, who have progressed after or are intolerant to the standard of care therapy. XL092 is a next-generation tyrosine kinase inhibitor (TKI) in development for multiple advanced tumor types.

“There is a significant need for new treatment options for the majority of metastatic CRC patients, who do not have microsatellite instability-high or mismatch-repair deficient disease and whose tumors do not respond to immunotherapy alone,” said Vicki L. Goodman, M.D., Executive Vice President, Product Development & Medical Affairs, and Chief Medical Officer, Exelixis. “Following recent promising data evaluating cabozantinib in combination with immunotherapies in colorectal cancer, we are thrilled to initiate our first phase 3 pivotal trial for XL092, our next-generation tyrosine kinase inhibitor. We look forward to learning more about how XL092 in combination with atezolizumab may benefit patients with metastatic colorectal cancer.”

STELLAR-303 is a global, multicenter, randomized phase 3 open-label study that will enroll approximately 600 patients with documented RAS status. Patients will be randomized 1:1 to receive either XL092 in combination with atezolizumab or regorafenib. The primary objective of the study is to evaluate the efficacy of the combination in patients with RAS wild-type disease; exploratory endpoints include examining efficacy in those with RAS-mutated disease. The primary endpoint is overall survival. Secondary endpoints include progression-free survival, objective response rate and duration of response per Response Evaluation Criteria in Solid Tumors version 1.1 as assessed by the investigator.

Previously announced results from two studies of cabozantinib in combination with immunotherapies for the treatment of advanced CRC supported Exelixis’ decision to pursue clinical development of XL092 in this setting. The trial is sponsored by Exelixis, and Roche is supplying atezolizumab.

https://www.biospace.com/article/releases/exelixis-announces-initiation-of-the-stellar-303-phase-3-pivotal-trial-evaluating-xl092-in-patients-with-metastatic-colorectal-cancer/

AbbVie Submits Supplemental NDA for Atogepant Label Expansion for Migraine Prevention

 Submission is based on pivotal Phase 3 PROGRESS chronic migraine study evaluating atogepant (QULIPTATM) in adult patients that met primary endpoint of statistically significant reduction from baseline in mean monthly migraine days compared to placebo

-       If approved, atogepant (QULIPTA) would be the first gepant (oral calcitonin gene-related peptide [CGRP] receptor antagonist) with a broad preventive treatment of migraine indication that expands treatment to patients with chronic migraine

-       Label expansion would make AbbVie the only company to offer two preventive treatments for those with chronic migraine, atogepant (QULIPTA) and onabotulinumtoxinA (BOTOX®)

https://www.biospace.com/article/releases/abbvie-submits-supplemental-new-drug-application-to-u-s-fda-for-atogepant-qulipta-to-support-label-expansion-for-the-preventive-treatment-of-migraine/