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Tuesday, October 12, 2021

New Alzheimer’s drug threatens state Medicaid budgets

 new drug that was supposed to be a lifeline for thousands of individuals and families struggling with the tragic impacts of Alzheimer’s disease is evolving into a millstone around the neck of Medicaid, America’s largest safety net health insurer.

The Medicaid program, which today connects one in every four Americans to the health care they need, is an essential part of the U.S.’s health care fabric. But a recent decision by the Food and Drug Administration to approve Aduhelm, an unproven and exceptionally costly new drug to treat the symptoms of early Alzheimer’s disease, could threaten Medicaid’s ability to continue to serve the millions of people who rely on the program.

Medicaid operates independently in each of the nation’s 56 states and territories. It is a “first responder” during economic downturns and for natural disasters and pandemics. It is the largest provider of mental health and behavioral health services. Forty percent of all children rely on Medicaid for comprehensive health care benefits, and the program finances 50% of all births in the U.S.

Medicaid now overshadows its sister program, Medicare, in terms of total number of people covered. Medicaid also supports the Medicare program for low-income seniors and individuals with disabilities by paying for its sizable premiums, co-pays and deductibles. It also pays for comprehensive nursing home care and home and community-based options for seniors with low incomes.

There’s no question that curing or treating Alzheimer’s, or at the very least delaying its onset, is a priority for all sectors of the health care landscape, as 5 million Americans and their families are currently living with the disease. But the most recent development in this sphere could burden state Medicaid programs with an expensive product with questionable evidence of effectiveness.

The FDA’s approval of Aduhelm, a drug meant to slow the progression of the disease, has been touted as a potential cost saver for the Medicaid program by reducing the number of seniors with dementia who will need long term care. It’s likely to do just the opposite.

The Medicare program has just embarked on a comprehensive review of Aduhelm, which may lead to the federal program deciding to cover it for a narrow set of individuals, or not cover it at all. This may well be the smart decision for a product with a $56,000 price tag and questionable evidence of success. The Institute for Clinical and Economic Review believes a price between $3,000 and $8,400 is more appropriate.

A decision by Medicare not to cover Aduhelm will shift all of the costs entirely to the Medicaid program, which is required by federal law to cover all FDA-approved drugs, no matter how poorly they work. Based on a survey conducted on behalf of the National Association of Medicaid Directors, which I direct, Medicare’s decision not to cover Aduhelm would cost the Medicaid program an estimated additional $1.9 billion in fiscal year 2022.

State Medicaid programs can ill afford to waste valuable resources — particularly in the midst of a pandemic — on high-cost, low-value treatments. Compounding this budget reality is the fact that Aduhelm is not intended to cure Alzheimer’s, so in all likelihood individuals who are prescribed it will take it for the rest of their lives, compounding the long-term costs of covering it.

The federal government must take immediate action to ensure that these costs are not irresponsibly shifted onto the Medicaid program. One straightforward reform might be to allow state Medicaid programs the authority to cover — or not cover — Aduhelm in alignment with Medicare’s decision.

Aduhelm is just the most recent example of the challenges Medicaid faces in sustaining its ability to provide high-value and cost-effective care for the tens of millions of Americans who rely on it. There are further reforms that will still need to be made as future products like Aduhelm that carry both astronomical price tags and little evidence of their clinical effectiveness receive FDA approval. Medicaid must have a more sensible, longer-term solution to how it covers and pays for those products.

Matt Salo is the executive director of the National Association of Medicaid Directors.

https://www.statnews.com/2021/10/12/new-alzheimers-drug-threatens-state-medicaid-budgets/

Takeda taps Poseida for 2nd $1B-plus gene therapy pact

 Takeda's fervor for gene therapies hit a new peak Tuesday in a research collaboration that could skyrocket to $3.6 billion for Poseida Therapeutics. 

The Japanese Big Pharma is willing to dole out that massive haul for six to eight non-viral, in vivo gene therapies that target liver and hematologic diseases, Poseida said Tuesday.

While this is Poseida's first major collaboration, Takeda is a longtime proponent of linking arms with biotechs. Just last week, Takeda said it would dish out up to $1.12 billion for Selecta Biosciences' technology to produce gene therapies for lysosomal storage disorders. That follows a $303 million gene med pact with Genevant in August, also focused on liver diseases. 

The Poseida collab includes $45 million upfront, $125 million in preclinical milestones, up to $2.7 billion if the six programs come to fruition and the grand total of $3.6 billion if all eight therapies reach their milestones. Tiered royalties will be in the double digits. 

The San Diego biotech will pony up its genetic engineering platform, including biodegradable DNA and RNA nanoparticle delivery technology, to help Takeda create gene therapies amid growing investor interest in regenerative medicine. One of the therapies involved in the deal is Poseida's hemophilia A program, which is in preclinical studies at the moment. 

Timelines and specific indications were kept under wraps, even in a Securities and Exchange Commission filing, as none of the programs have entered human trials. 

Non-viral gene therapy is especially of interest because it evades the safety issues associated with adeno-associated virus-based treatments in the field, which have come under increasing pressure from the FDA after an advisory committee marathon was held to look at Novartis' Zolgensma and others.

Under the agreement, Poseida will lead research activities until candidates are selected. Takeda then takes the reins for all further development and sales work. 

https://www.fiercebiotech.com/biotech/billions-club-takeda-taps-poseida-for-second-1b-plus-gene-therapy-pact-2-weeks

Idorsia’s Fabry flop puts focus on gene therapies

 The pivotal failure yesterday of Idorsia’s Fabry disease project lucerastat exposes a dearth of other projects in the late-stage Fabry pipeline, even if it is unlikely to spell the end of the world for the Swiss group.

True, enzyme-replacement therapies are well established, but these do not prevent disease progression and are burdensome, with patients needing infusions every two weeks. Gene therapy is now the main hope for patients seeking an alternative, but recent safety scares in the field could raise doubts about this approach.

Sellside consensus compiled by Evaluate Pharma shows enzyme-replacement therapies, as well as Amicus’s Galafold, continuing to dominate this space in 2026 – although this might in part reflect the early-stage nature of the gene therapy projects. As for Idorsia, it has more important upcoming catalysts, and ended yesterday down a relatively modest 4%.

Annual sales ($m)The Fabry disease outlookST-920 - SangamoFLT190 - FreelineLucerastat - IdorsiaAVR-RD-01 - AvrobioReplagal - TakedaGalafold - AmicusFabrazyme - Sanofi202020212022202320242025202601k2k3k4kEvaluate2021 Galafold - Amicus: 313

Fabry disease is caused by mutations in the GLA gene, which encodes the enzyme alpha-galactosidase A. This enzyme usually breaks down a fatty substance called globotriaosylceramide (Gb3), but in Fabry patients Gb3 builds up, causing symptoms such as pain crises, hearing loss and kidney and heart disease. The disease varies in severity depending on patients’ enzyme activity levels.

Replacing the enzyme is a mainstay of care, but the aforementioned issues mean that the search is still on for something better. Amicus’s Galafold, an oral drug designed to stabilise alpha-gal A, gained accelerated approved in 2018, but is only indicated for patients with certain GLA mutations.

Idorsia’s lucerastat, meanwhile, is an oral glucosylceramide synthase inhibitor designed to reduce Gb3 accumulation. Data from the Modify study suggest it does just that: Idorsia said yesterday that there was a “substantial and consistent reduction of plasma Gb3”; however, the trial did not meet its primary endpoint, reduction in neuropathic pain at six months, measured using the modified brief pain inventory-short form 3 score.

Jefferies analysts previously noted that this was an unusual endpoint, versus the more traditional Fabry outcomes of kidney or heart function, and this could provide a reason for the failure.

Idorsia does not seem to have thrown in the towel on lucerastat just yet. The group said more data, including results from an open-label extension study, would help inform a decision on the project’s future. But Jefferies says a path forward looks unlikely.

The Swiss group has other irons in the fire. It is expecting a US approval decision in the first quarter of next year on its insomnia project daridorexant, and data are due this quarter from a phase 2b trial of the sphingosine 1-phosphate receptor modulator cenerimod in systemic lupus erythematosus.

However, daridorexant’s pivotal data were mixed, and lupus is a notoriously tough nut to crack.

Gene therapies

If this is the end for lucerastat it will take out a project that had been expected to become the fifth-biggest seller in Fabry by 2026, according to Evaluate Pharma.

There is not much else on the near-term horizon. Protalix and Chiesi still hope for approval of PRX-102, which received an FDA complete response letter in April over manufacturing issues. However, this is merely a long-acting enzyme replacement therapy.

Sanofi’s venglustat completed a Fabry trial in 2016, but the group has yet to take the project further in the disease, despite still listing it in its pipeline. In any case this works similarly to lucerastat, so hopes cannot now be high.

This leaves a clutch of gene therapies, which all aim to deliver a working copy of the GLA gene and provide a once-and-done treatment. It is early days, but several are set to yield phase 1/2 data by the end of this year.

A number of gene therapy scares this year have raised the question about the safety of this approach more broadly – and raise the question of whether Fabry patients will want to go down this route given the availability of enzyme replacement therapies.

Perhaps things will have become clearer by the time the Fabry gene therapy assets have reached later-stage development but, until then, the biggest beneficiaries from lucerastat’s failure look like Amicus and the enzyme-replacement players.   

Fabry disease pipeline
ProjectCompanyDescriptionNote
Filed
Pegunigalsidase alfa (PRX-102)Protalix/ChiesiLong-acting IV alpha galactosidase regulatorCRL received Apr 2021; resubmission planned
Phase 3
LucerastatIdorsiaOral glucosylceramide synthase inhibitorFailed Modify Oct 2021
Phase 2
Venglustat (GZ402671)SanofiOral glucosylceramide synthase inhibitorPh2 completed 2016; still listed in pipeline
Phase 1/2
4D-3104D MolecularGLA gene therapy (AAV vector)NCT04519749; initial data due Q4 2021
FLT190FreelineGLA gene therapy (AAVS3 vector)Marvel-1; data from mid-dose cohort due YE 2021
AVR-RD-01AvrobioGLA gene therapy (lentiviral vector)Fab-GT; safety data on 9 pts due Q4 2021, efficacy data due at World Symposium Feb 2022
ST-920SangamoGLA gene therapy (AAV2/6 vector)Staar; escalating to third dose but initial data no longer expected in Q4 2021
Source: Evaluate Pharma & clinicaltrials.gov.

https://www.evaluate.com/vantage/articles/news/trial-results/idorsias-fabry-flop-puts-focus-gene-therapies

Protara : FDA Clears IND Application for TARA-002 in Bladder Cancer

 Protara Therapeutics Inc. said the U.S. Food and Drug Administration cleared its investigational new drug application for TARA-002 for the treatment of non-muscle invasive bladder cancer, sending shares higher in premarket trade.

Protara, a clinical-stage company focused on cancer and rare diseases, said it expects to initiate a Phase 1 clinical trial of TARA-002 in adults with high-grade NMIBC by the end of this year.

The primary objective of the trial is to evaluate the safety, tolerability and preliminary signs of anti-tumor activity of TARA-002, with the goal of establishing a maximum tolerated dose and recommended dose for a future Phase 2 clinical study.

https://www.marketscreener.com/quote/stock/PROTARA-THERAPEUTICS-INC-18411179/news/Protara-Therapeutics-FDA-Clears-IND-Application-for-TARA-002-in-Bladder-Cancer-36659743/

Quanterix Shares Rally After Simoa Test Gets FDA Breakthrough Tag

 Shares of Quanterix Corp. rose nearly 15% in early trading Tuesday after the company received U.S. Food and Drug Administration breakthrough-device designation for its Simoa phospho-Tau 181 blood test as an aid in diagnostic evaluation of Alzheimer's disease.

The Billerica, Mass., provider of digital health solutions said proposed indications under the designation include use of the test results in patients ages 50 and up presenting with cognitive impairment who are being evaluated for Alzheimer's and other causes of cognitive decline.

The FDA's breakthrough-devices program aims to expedite the development and review of technology that offers significant advantages over existing approved products.

https://www.marketscreener.com/quote/stock/QUANTERIX-CORPORATION-38934439/news/Quanterix-Shares-Rally-After-Simoa-Test-Gets-FDA-Breakthrough-Designation-36662087/

NRx Pharmaceuticals Up on Zyesami Progress

 NRx Pharmaceuticals Inc. shares were recently up 44% to $9.75 following updates about Zyesami, in development for treatment of Covid-19 patients with respiratory failure.

The company said a revised Investigational New Drug module was submitted to the U.S. Food and Drug Administration, containing documentation that confirmed Nephron Pharmaceuticals Inc. is prepared to supply Zyesami on a commercial scale.

Meanwhile, NRx was notified that a European auditor completed an inspection at a separate manufacturing facility with no adverse findings.

In July, the company received the exclusive worldwide right to develop and market the BriLife Covid-19 vaccine developed by the Israel Institute for Biological Research.

https://www.marketscreener.com/quote/stock/NRX-PHARMACEUTICALS-INC-38908842/news/NRx-Pharmaceuticals-Up-44-on-Zyesami-Progress-36664004/

Glaxo on track with consumer split as buyout report boosts shares

 

GlaxoSmithKline is "firmly on track" to spin off its consumer health business next year, the British drugmaker said on Tuesday, after Bloomberg News reported the unit could attract bids from private equity firms such as Advent, CVC and KKR.

The division, which makes Sensodyne toothpaste, and Advil and Panadol painkillers, could also draw interest from big pharmaceutical and consumer goods companies, the report said , citing unidentified people with knowledge of the matter.

It added the unit could be valued at 40 billion pounds ($54 billion) or more.

A GSK spokesperson declined to comment on whether the company had received takeover interest in the division, a joint venture with U.S. drugmaker Pfizer.

The report sent London-listed GSK's shares as much as 4.8% higher to 1,460.2 pence.

"GSK is far advanced with its plan for the separation of Consumer Healthcare," the GSK representative said, adding the drugmaker was on course for the split in mid-2022.

The company set out plans in June to turn the consumer arm into a separately listed company to focus on its underperforming drugs business, and has defended those plans after activist investor Elliott suggested some changes including that GSK remained open to potentially selling the consumer business.

"The feedback we have received from our shareholders is that they are very keen to own the new Consumer Healthcare company as a listed entity through the demerger ... The GSK board will fulfil its fiduciary duties to evaluate any alternative options," GSK's spokesperson said.

Under GSK's plan, shareholders will receive stock in the new consumer health group amounting to at least 80% of the 68% stake that GSK currently owns in it. Pfizer owns the remaining 32%.

New GSK would sell the remaining 20% stake "in a timely manner," the group has said. Pfizer has also said it would seek to exit its shareholding.

Elliott, which in July confirmed holding a significant stake in GSK, said then that a conservative estimate would value GSK's shareholding in the consumer unit at about 34 billion pounds - working out to roughly 50 billion pounds overall.

Brokerage Jefferies has valued it at 45 billion pounds.

Another activist investor, Bluebell Capital Partners, which holds a smaller stake in GSK, said last month the consumer arm should attract interest from trade buyers and, potentially, private equity investors.

Elliott has said a sale of the unit to an industry peer would command a "meaningful premium" to its estimated value due to potential synergies of up to 10% of the business's revenues.

Separately, Bluebell said in an open letter to GSK Chairman Jonathan Symonds dated Oct. 11, that both he and Chief Executive Emma Walmsley should be replaced, voicing disappointment over an Oct. 7 investor event.

"We completely reject the content and claims made in this letter, which are not representative of the discussion at the meeting or the majority of our shareholders' views," GSK said in response.

https://www.marketscreener.com/quote/stock/GLAXOSMITHKLINE-PLC-9590199/news/GlaxoSmithKline-GSK-on-track-with-consumer-split-as-buyout-report-boosts-shares-36657991/