Vaxcyte Catapults As It Looks To Take On Pfizer, Merck

Vaxcyte (PCVX) shares rocketed to a record high Tuesday after the biotech company delivered "stunning" test results for its pneumococcal vaccine.

In a study of 1,015 adults age 50 and older, the shot protected against 31 strains of pneumococcal disease. Pneumococcal disease can cause meningitis, pneumonia, ear and sinus infections, and other illnesses.

Importantly, the vaccine called VAX-31 offered the same or better protection against the 20 strains blocked by Pfizer's (PFE) Prevnar 20. Leerink Partners analyst David Risinger said the Street expected the Vaxcyte shot to lag Prevnar 20 on three of the 20 strains. But the high and middle doses didn't miss on any.

Now, Vaxcyte is planning to move into Phase 3 testing.

"We believe the data support strong likelihood that VAX-31 could achieve majority market share in what we expect to be a more than $10 billion pneumococcal conjugate vaccine market in 2030-plus," Risinger said in a report.

In early trades on today's stock market, Vaxcyte stock launched more than 43% to 116.20. Shares opened at their highest-ever point. Pfizer stock, on the other hand, sank 1.7% to 28.51.

Vaxcyte Takes On Pfizer And Merck

Risinger described Vaxcyte's results as "stunning" and reiterated his outperform rating on shares.

Mizuho Securities analyst Salim Syed said Vaxcyte's study offers a best-case scenario. A high dose of VAX-31 led to better immune responses against 18 of the 20 strains included in Prevnar 20. The middle dose outperformed on 13 of the 20 strains.

For the 11 strains note included in Prevnar 20 and unique to VAX-31, all three doses tested met the superiority criteria, Vaxcyte said in a news release.

Syed estimates this could ultimately be a $24 billion market. Merck (MRK) also sells Capvaxive, a vaccine that protects against 21 strains of pneumococcal disease. Merck shares fell 1.1% to 117.15.

https://www.investors.com/news/technology/vaxcyte-stock-pfizer-prevnar-20-pneumococcal-vaccine/

Illumina wins Grail battle in blow to EU merger power

 U.S. gene sequencing company Illumina on Tuesday won its court fight against the European Union's investigation of its $7.1 billion purchase of cancer diagnostic test maker Grail, a ruling set to curb Brussels' merger powers.

Illumina, which founded Grail and spun it off in 2016 only to re-acquire it in 2021 for $7.1 billion, had fought against the European Commission's decision to wield a rarely-used power called Article 22 to assess the deal even though it was below the EU's merger revenue threshold.

The case has been closely watched by companies wary of EU scrutiny of minor deals but which regulators fear could be so-called killer acquisitions in which big companies buy startups to shut them down.

However, it may have limited implications for Illumina, which spun off Grail again in June to comply with an EU order, keeping a minority stake of 14.5%.

The EU's General Court had in 2022 ruled in favour of the Commission after Illumina challenged the EU merger review that was triggered by requests from several EU countries.

The higher Court of Justice of the European Union (CJEU), however, sided with Illumina.

"The Court of Justice sets aside the judgment of the General Court and annuls the decisions by which the Commission accepted requests from national competition authorities seeking the examination of the proposed concentration," CJEU judges said.

"The Commission is not authorised to encourage or accept referrals of proposed concentrations without a European dimension from national competition authorities where those authorities are not competent to examine those proposed concentrations under their own national law," they said.

The Commission, the EU's competition enforcer, blocked the deal in 2022 and ordered Illumina to divest Grail. It also fined Illumina 432 million euros ($478 million) for closing the deal in 2021 before securing its approval.

Illumina said the CJEU ruling meant it did not have to pay the fine.

"Today’s judgment confirms Illumina’s longstanding view that the European Commission exceeded its authority by asserting jurisdiction over this merger. The basis for the 432 million euro fine has now been removed and will no longer be payable," it said.

The ruling is final and cannot be appealed.

The Commission said it would carefully study the judgment and its implications.

"More generally, we will consider the next steps to ensure that the Commission is able to review those few cases where a deal would have an impact in Europe but does not otherwise meet the EU notification thresholds," it said.

The cases are Cases C-611/22 P Illumina v Commission and C-625/22 P Grail v Commission.

https://www.aol.com/illumina-wins-grail-battle-blow-075036897.html

Beyond Rare Disease: Wet AMD Gene Therapy Could Reach Millions

With gene therapies by REGENXBIO and AbbVie, Adverum and others in mid- or late-stage trials, this therapeutic class could soon be an option for this common cause of blindness in the elderly.

As gene therapies continue to transform the rare disease treatment landscape, a new generation is on the cusp of breaking through against a highly prevalent disease indication—wet age-related macular degeneration.

Age-related macular degeneration (AMD) is the most common cause of vision loss in people over 60. The advanced stage of the disease, wet AMD, occurs in around 10% of cases and results in 90% of legal blindness. In 2019, around 1.5 million people in the U.S. were living with wet AMD.

The potential reach of a gene therapy in this common disease space is in stark contrast to the current approved gene therapies for rare disease. REGENXBIO and partner AbbVie are currently conducting the “largest gene therapy program ever run” for their wet AMD candidate, REGENXBIO Chief Medical Officer Steve Pakola told BioSpace.

“[Wet AMD gene therapy] is a pretty unique situation,” said Laurent Fischer, CEO of Adverum, a biotech with a mid-stage candidate in the works. Instead of a therapy that costs millions of dollars for thousands of people, he anticipates a price tag of tens of thousands of dollars for millions of people.

Gene Therapy Turns Eye Into Drug Biofactory

Currently approved gene therapies focus on repairing or replacing a faulty gene that causes the disease. In wet AMD, there is no defective gene, so companies are developing gene therapies to deliver an effective medicine to the eye, Rahul Khurana, a retina specialist at Northern California Retina Vitreous Associates, told BioSpace.

Wet AMD is currently treated by anti-VEGF therapies, which block the molecules that lead to the leak of blood or fluid under the retina that blurs the central vision. Khurana said that while these therapies are effective, the burden of ongoing treatment in clinical practice is problematic, with patients regularly needing anti-VEGF injections. Khurana recently published a study showing that one in nine AMD patients treated with anti-VEGF injections became “lost to follow up” and one in seven are not persistent with therapy.

“Gene therapy shows a lot of promise for a one-time therapy, or a longer duration therapy, to deliver medicine so patients do not keep returning for regular injections,” Khurana said. “It’s a very creative approach.”

Gene therapies by Adverum, 4D Molecular Therapeutics, and REGENXBIO in collaboration with AbbVie are in mid- to late-stage clinical trials. Each involves injections to deliver a therapeutic protein but differs in where those injections are given—behind the retina at the back of the eye (sub-retinal), between the sclera and choroid near the eye’s outer surface (suprachoroidal) or into the fluid that fills the inside of the eye (intravitreal).

Sub-Retinal Injection

With a pivotal trial already underway, REGENXBIO and AbbVie are furthest along of all the wet AMD gene therapies in development. Pakola said the companies are on track to submit global registration applications in the first half of 2026.

REGENXBIO/AbbVie’s ABBV-RGXX-314 is an AAV8 vector containing a gene encoding a monoclonal anti-VEGF antibody fragment. After injection, the retinal tissue produces the anti-VEGF therapeutic protein for an extended timeframe, Pakola explained.

While follow up is ongoing for long-term efficacy, the partners have seen stable disease control beyond three and four years, with a dramatic reduction in injection burden, Pakola said. He added that results so far show an 80% reduction in required injections.

According to Pakola, AAV8 is one of the most clinically validated vectors in terms of safety and efficacy. With the prescribed seven-week course of prophylactic topical steroids, REGENXBIO has not seen any intraocular inflammation. The sub-retinal delivery method keeps the gene therapy payload at the target tissue, minimizing off-target and systemic exposure, he explained.

Sub-retinal delivery is the most invasive of the three approaches as it requires a surgical procedure. The therapy is administered through a vitrectomy, a surgery common to retinal surgeons that takes ten minutes or less, Pakola said.

Khurana, who has been involved with REGENXBIO and AbbVie’s clinical trials, believes his patients who require regular injections are “very open to” a one-time surgical option, though he noted that it could be limited to those who are healthy enough for outpatient surgery and willing to be put under anesthesia.

In addition to its sub-retinal program, the partners are also developing a suprachoroidal route of administration for ABBV-RGX-314, currently in Phase II trials. A needle is inserted into the thin space between the sclera and choroid of the eye for targeted delivery to the retina without surgery. The delivery is compartmentalized, spreading broadly to the retina but not to the vitreous or other parts of the eye, Pakola explained.

Intravitreal Injection

The third delivery option follows the approach used by current anti-VEGF treatments: intravitreal injection—into the vitreous humor of the eye. This is the approach taken by Adverum, whose gene therapy ixoberogene soroparvovec (ixo-vec) comprises a proprietary vector capsid carrying a coding sequence for aflibercept, the VEGF-A antagonist in Regeneron’s Eylea. Fischer told BioSpace that ixo-vec elicits production of the Eylea drug product in patients’ eyes at low levels for years.

“We’re the first to develop this vector that’s been modified to be able to be administered in the front of the eye,” Fischer said, its delivery mimicking the current in-office standard-of-care. “Intravitreal delivery has been the holy grail of ocular gene therapy because it fits in the very busy practices that see up to 100 patients a day.”

Overall, clinical data show that ixo-vec has led to a 90% reduction in annualized injections. After 26 weeks, 76% of patients who received the planned Phase III dose were injection free with disease control. In patients with the greatest burden of care—those receiving around ten injections per year—more than 50% are free of injections three years after treatment with ixo-vec, Fischer said. With the use of prophylactic corticosteroids, 100% of patients had no or minimal inflammation.

“It’s really a functional cure, disease modifying for most patients, which is really transformative,” Fischer said. Ixo-vec will advance to pivotal studies next year.

Meanwhile, 4D Molecular Therapeutics (4DMT) is also developing an intravitreal injection gene therapy called 4D-150, designed to deliver the genes for both aflibercept and an RNA molecule to suppress VEGF-C expression. Like Adverum, 4DMT has designed its own novel, customized vectors to support intravitreal dosing, CEO David Kirn told BioSpace in an email. The company’s Phase II data show an 89% reduction in annualized injection rate with 77% of patients injection-free after 24-weeks, and the treatment was safe and well-tolerated with a prophylactic, topical steroid regimen.

4DMT is currently working with the FDA and EMA under accelerated program designations to finalize its Phase III clinical design, with expectations to initiate the trial in the first quarter of 2025, Kirn said.

‘Immune Privileged’

Gene therapies are typically a one and done treatment. Due to viral vector delivery, gene therapy causes an immune response that prevents redosing.

But the eye is “somewhat immune privileged,” Fischer said. Even though the viral delivery will create an immune response in one eye, it does not impact the ability to treat the other eye, he explained. While 42% of wet AMD patients eventually have disease in both eyes, it often develops months or even years after the first eye was treated.

With this in mind, Adverum is planning to enroll previous trial participants to have their second eye treated with ixo-vec. The ability to treat both eyes asynchronously while avoiding a systemic immune response has already been demonstrated in a non-human primate. Fischer believes the FDA will want to see bilaterally treated patient data in the eventual BLA filing in order to obtain approval.

REGENXBIO is also running a study where patients who have had one eye treated in a prior study can enroll to have the other eye addressed. Twenty patients have been treated with results expected in the next six months, Pakola said.

A Widely Accessible Gene Therapy?

Whereas rare disease gene therapies that replace or correct a faulty gene carry multi-million-dollar price tags, the cost of wet AMD treatment will be much lower, Pakola said. “Cost isn’t a barrier.”

And while there are existing therapies for wet AMD, Pakola noted that payers have been receptive to the value proposition of gene therapy because the burden of ongoing treatment is so high.

Fischer pointed out that Medicare Part B spends 13% of its annual budget on AMD drugs alone—around $5 billion. If a patient lives years past treatment, gene therapy could ultimately save Medicare money, he said.

“We’re going from incremental benefits to truly transformational with gene therapy,” Fischer said. “And I think that’s . . . the power of regenerative medicine and gene therapy.”

https://www.biospace.com/drug-development/beyond-rare-disease-wet-amd-gene-therapy-could-reach-millions

FDA Action Alert: Travere, Avadel and Roche

 

The FDA has three regulatory milestones in the next two weeks, including a decision on a subcutaneous formulation of an effective multiple sclerosis therapy.

September is starting off slow for the FDA, which has just three big catalysts in the next two weeks, including one for a rare kidney disease drug.

Read below for more.

Travere Seeks Full Approval for IgAN Treatment Filspari

Travere Therapeutics is eyeing full approval for its IgA nephropathy (IgAN) therapy Filspari (sparsentan). The FDA’s decision is due on September 5.

IgAN is a rare, autoimmune disease that afflicts the kidneys and arises when antibodies accumulate in the glomeruli, leading to inflammation and eventually organ damage. Patients with IgAN often have blood and protein in their urine. In its progressed form, IgAN can lead to kidney failure. There are currently no cures for the disease.

Travere’s answer to IgAN is Filspari, a non-immunosuppressive therapy that works by inhibiting the endothelin-1 and angiotensin II receptors, which are central to disease progression. The FDA granted Filspari accelerated approval in February 2023 based on proteinuria data from the Phase III PROTECT study, which showed the drug reduced protein levels in urine more than three times as much as the active control Avapro (irbesartan).

PROTECT continued to collect data to serve as Filspari’s confirmatory trial, but in September 2023, Travere reported that the trial “narrowly” missed its estimated glomerular filtration rate total slope endpoint.

Still, CEO Eric Dube at the time expressed confidence in Filspari, noting that the treatment “resulted in the largest sustained reduction in proteinuria and one of the slowest rates of eGFR decline in a controlled study of IgAN patients, to date”

Filspari’s label carries a boxed warning for hepatotoxicity and embryo-fetal toxicity. The drug, available only through a restricted distribution program, is contraindicated to pregnancy, angiotensin receptor blockers and endothelin receptor antagonists.

Avadel Pushes for Pediatric Expansion for Lumryz

By September 7, the FDA is expected to release its verdict on Avadel Pharmaceuticals’ supplemental New Drug Application for Lumryz (sodium oxybate), which seeks to expand its use to pediatric patients with narcolepsy.

Designed to be taken orally, Lumryz is an extended-release and suspension formulation of sodium oxybate, which is a depressant of the central nervous system. Its exact mechanism of action for narcolepsy is not completely known, according to its label, though Lumryz’s effects are likely mediated through GABA receptors on noradrenergic, dopaminergic and thalamocortical neurons.

The FDA approved Lumryz in May 2023 to address excessive daytime sleepiness and cataplexy—or the sudden temporary loss of muscle control—in patients with narcolepsy. However, the drug is currently only indicated for adults. It comes with a boxed warning for central nervous system and respiratory depression, as well as the risk of abuse and misuse.

In January 2024, Avadel released launch figures for Lumryz, touting around $19 million in net sales for the fourth quarter of 2023 alone and over 1,000 patients initiated on the oral drug. If approved for use in children, who account for 3% to 5% of all oxybate-treated patients, Avadel could push Lumryz’s revenues even higher, while also easing the burden of the disease on families and caregivers.

Aside from narcolepsy, the biotech is also developing Lumryz for idiopathic hypersomnia, for which a study is slated in the second half of 2024.

Roche’s MS Drug Awaits Verdict for Subcutaneous Use

Roche is developing a subcutaneous formulation of its anti-CD20 antibody Ocrevus (ocrelizumab) for the treatment of progressive and relapsing forms of multiple sclerosis (MS). The FDA’s decision is expected by September 13, according to the second-quarter business report of Halozyme, whose Enhanze technology was used in developing the subcutaneous injection.

Ocrevus, a recombinant humanized IgG1 monoclonal antibody, scored its first approval in 2017 for severe MS, and a shorter infusion time was greenlit in 2020. Though its exact mechanism of action is unknown, according to its label, Ocrevus is thought to target the CD20 surface antigen on B cells, in turn triggering cell death.

Roche backed its subcutaneous application with data from the Phase III OCARINA II study. In June 2023, the pharma revealed initial data from the trial, demonstrating that a 10-minute subcutaneous injection can achieve similar pharmacokinetics to the usual hours-long infusion of the currently approved formulation. The subcutaneous version also elicited similar levels of brain lesion control.

The company released more data from OCARINA II in April 2024, noting that 97.2% of patients treated with the subcutaneous injection achieved “near-complete suppression of relapse activity” through 48 weeks of follow-up. More than 90% of patients said they were satisfied or very satisfied with the subcutaneous formulation, while a similar percentage agreed that it was convenient or very convenient.

https://www.biospace.com/fda/fda-action-alert-travere-avadel-and-roche

UK Announces Partial Ban On Arms Exports To Israel

 The United Kingdom has announced it will suspend a portion of its current arms and defense sales to Israel, citing a "clear risk" to civilians and that they could be used to violate international humanitarian law.

Foreign Secretary David Lammy informed parliament Monday that the suspension will impact of 30 of 350 arms export licenses to Israel. The partial ban covers supplies "which could be used in the current conflict in Gaza" against Hamas. However, parts for F-35 fighter jets are exempt from the ban. He emphasized that the country still backs Israel's right to self-defense, and thus the UK is not enacting a blanket ban on all items.

"It is with regret that I inform the House [of Commons] today the assessment I have received leaves me unable to conclude anything other than that for certain UK arms exports to Israel, there does exist a clear risk that they might be used to commit or facilitate a serious violation of international humanitarian law," Lammy said, after conducing a review of shipments to Israel.

"We recognize, of course, Israel’s need to defend itself against security threats, but we are deeply worried by the methods that Israel’s employed, and by reports of civilian casualties and the destruction of civilian infrastructure particularly," he continued.

The Gaza Health Ministry has said that over 40,000 Palestinians have been killed in over ten months of war. Israel says a large percentage of the deceased are Hamas militants, while Palestinian sources assert the majority are women and children.

Analysts say this is not expected to have much of an impact on Israel's operations given that British exports only make up less than one percent of total external arms sales Israel receives.

Israel reacted with disappointment, anger, dismay. Israeli Foreign Minister Israel Katz lashed out Monday in wake of the UK decision, saying it "sends a very problematic message" to terrorist groups like Hamas and its supporters in Iran.

But Lammy had sought to emphasize in his comments it doesn't mean he believes Israel is guilty of war crimes or human rights abuses per se. "This is a forward looking evaluation, not a determination of innocence or guilt, and it does not prejudge any future determinations by the competent courts," he said.

Meanwhile, pressure from Washington to wrap up Gaza operations also could be growing...

Large and growing pro-Palestine protests which have gripped parts of London over the last weeks and months have been increasing in size and intensity, and are perhaps having an impact on Labour politicians.

https://www.zerohedge.com/geopolitical/uk-announces-partial-ban-arms-exports-israel

New JAMA paper shows: it is vaccine myocarditis PLUS covid myocarditis

 There is a new paper in JAMA from the French, which tries to compare the damage from COVID myocarditis against idiopathic or conventional myocarditis.

I will discuss it more in a future post, but that question is a bit boring. It would be like if someone invented a hovercraft and then compared hovercraft injuries to airplane crash injuries. Sure, hovercraft injuries may be less severe, but I still don’t want to be injured in your hovercraft!

But buried in the supplement is something more interesting. Remember, we have long debated which is worse: myocarditis from vaccination or myocarditis from COVID (without vaccination). Shown in the figure.

One important point however is that vaccines don’t stop COVID transmission, and if you take the vaccinated pathway, you can get both! Well, these authors accidentally reveal the information in the Supplementary Appendix. Here are the numbers from France (these are hospitalizations)

The paper doesn’t say the DENOMINATOR. So these are raw counts. You would have to postulate an 80% vaccination rate for these 2 to be roughly equal (which is probably pretty close to what they got in France*). But remember, this is not AGE ADJUSTED.

If they authors released the information by age group, it would be OBVIOUS that for young men, vaccination and boosting leads to WAY more myocarditis.

*Let’s do some math to try to guess about denominators. In France 55 million people / 67 million got at least 1 covid shot = 82%. But not all of those were mRNA, AZ and J&J were also given. PS It would be easy to figure out but sadly…..

https://www.drvinayprasad.com/p/a-new-jama-paper-shows-it-is-vaccine