JPM23: Bluebird touts gene therapy launch progress, extends cash runway to 2024

 Before bluebird bio nabbed a pair of gene therapy FDA approvals for last summer, the company’s future looked uncertain. Entering 2023, the gene therapy specialist appears to be standing on stronger ground. 

In a corporate update Monday, bluebird said it has treated the first commercial patient with beta thalassemia gene therapy Zynteglo. The company says it’s seeing “significant patient demand” for the newly approved therapy and expects to record the first sales from the product in the first quarter of this year. 

Zynteglo won an FDA approval last August to treat patients with beta thalassemia who require regular red blood cell transfusions. As a one-time gene therapy, the drug carries a multimillion-dollar price tag. In a bid to stand by the med’s real-world results, bluebird is offering outcomes-based pricing to payers. 

On that front, bluebird on Monday said the three largest pharmacy benefit managers in the U.S. have inked outcomes-based agreements for the therapy. The company says 190 million patient lives in the U.S. are covered under “favorable” policies for the medicine. 

Meanwhile, bluebird has activated 10 gene therapy treatment centers and is onboarding another 15, the company said. By the end of the year, the company expects to have 40 to 50 treatment centers in its nationwide network. 

As for Skysona, the company’s cerebral adrenoleukodystrophy (CALD) gene therapy, bluebird said cell collection for the first patient is scheduled for this month. That drug won an FDA approval last September and boasts a $3 million price tag. 

With the launches underway, bluebird expects to burn between $270 million and $300 million in cash this year. Thanks to the company's recent sales of priority review vouchers that netted nearly $200 million, plus other assets on hand, bluebird figures it can operate at least into the first quarter of 2024. 

That outlook marks an improvement from last year, when the company warned that its cash needs “raise substantial doubt regarding its ability to continue as a going concern." Previously, the company had to pull out of the European market over a pricing dispute with officials there, and its U.S. commercial outlook wasn’t always a sure bet before the FDA nods. 

Aside from its approved drugs, the company also sees a big opportunity in its lovo-cel candidate for sickle cell disease. The drugmaker expects to submit the candidate to the FDA in the first quarter of 2023 after completing vector and drug product analytical comparability studies late last year.   

The update comes as the J.P. Morgan Healthcare Conference kicks off in San Francisco. Bluebird CEO Andrew Obenshain is scheduled to speak at the conference on Thursday, but the company likely didn’t want the first day of the conference to pass without touting its recent progress. 

https://www.fiercepharma.com/pharma/jpm23-bluebird-touts-gene-therapy-launch-progress-extends-cash-runway-2024

Bristol Myers Squibb, Pfizer turned away from SCOTUS in high-profile cases

 Battling against an industry rival and the U.S. government, respectively, Bristol Myers Squibb and Pfizer have been quite busy in the courts. But now both of their efforts have ended in losses at the United States' top court.

Bristol Myers Squibb has come up short in its last-ditch effort to get the U.S. Supreme Court to review its decision from two months ago when it declined to hear its patent case against Gilead Sciences. Juno Therapeutics, Inc. versus Kite Pharma, Inc. was among (PDF) a laundry list of cases under the heading “rehearings denied,” that the Supreme Court released on Monday. 

The case surrounds Gilead’s cell therapy Yescarta, which is on its way to blockbuster status after generating $317 million in sales in the third quarter of last year.

The intellectual property case dates to 2017 when BMS’s subsidiary Juno combined with Sloan Kettering Institute for Cancer Research to sue Gilead’s subsidiary Kite.

The plaintiffs argued that Kite copied research from Sloan Kettering in developing Yescarta, a CAR-T treatment for lymphoma. A federal jury in 2019 found Gilead at fault and ordered the company to pay $752 million to Juno and Sloan Kettering. Kite’s attempts to overturn the verdict were so unconvincing that in April 2020, a judge increased BMS’ award to $1.2 billion, ruling that Kite’s infringement was “willful.”

But in 2021, a federal appeals court overturned the massive verdict against Gilead. At the time, a three-judge panel ruled an earlier ruling favoring Juno was “not supported by substantial evidence.”

Since then, BMS has battled the result unsuccessfully. Two months ago, the Supreme Court declined to hear the case. Monday’s decision reinforces that decision.

As for Pfizer, the Supreme Court declined to take up the New York pharma giant's case against the United States Department of Health and Human Services. In that lawsuit, Pfizer asked the Supreme Court to review whether its prospective program to help Medicare patients pay out-of-pocket costs for its tafamidis drugs Vyndaqel and Vyndamax would run afoul of federal anti-kickback laws. 

Vyndaqel/Vyndamax cost $225,000 a year before discounts, and, under Medicare’s formula, patients are responsible for a co-pay of about $13,000 per year. Pfizer’s proposed assistance program would lower the out-of-pocket cost to $35 per month, according to the company. 

The Department of Health and Human Services (HHS) rejected Pfizer’s proposal in 2019, ruling that such an arrangement would violate a criminal ban on financial support to patients for a federally reimbursed healthcare product.

After Pfizer sued to overturn that verdict, it suffered two consecutive losses, which prompted the company to petition the Supreme Court in July. But now the court has said it isn't interested in taking up its case.

"(The company) believes that providing copay assistance represents an equitable way to lower out-of-pocket costs for eligible patients who receive their prescriptions through Medicare Part D," Pfizer said in a statement. "We believe the company’s proposed copay program would have provided a mechanism to reduce out-of-pocket costs for eligible patients for the medicine their doctors have already prescribed and is consistent with the statutory framework under the Anti-Kickback Statute. Copay assistance would help ensure that financially needy Medicare patients could afford access to Tafamidis, a life-extending medication that is the only FDA-approved treatment for ATTR-CM."

https://www.fiercepharma.com/pharma/scotus-denies-bms-final-bid-rehear-appeal-against-gilead

JP Morgan 2023 – licensing deal flurry offers limited cash up front

 As well as three bolt-on deals with a European flavour day one of the JP Morgan healthcare conference today saw a flurry of smaller business development activities. However, none was enough to set the pulses racing: the biggest, a gene therapy-focused tie-up between Voyager and Neurocrine, was worth $175m in immediate cash, with $39m of this in equity, so it was hardly the sort of transaction deal bankers are desperate for as biotech enters an uncertain 2023. Lilly, Roche and Bayer signed discovery deals with Trexbio, Kronos and Recode respectively, worth a combined $75m in disclosed up-fronts. Meanwhile, Coherus picked up Klinge’s biosimilar version of Eylea, and Autolus licensed its Car-T switch to Cabaletta, mirroring an earlier non-exclusive licence with Bristol Myers Squibb. Elsewhere two companies buried bad news as Calithera moved to liquidate in the wake of telaglenastat’s failure, and Editas’s chief medical officer stepped down as the company discontinued work on NK cells at a precarious time for this field. The fact deals are happening is positive, of course, but signs from 2023’s first major investor conference are that buyers are increasingly able to dictate terms.

Selected licensing transactions on day one of JP Morgan
Deal source	Partner	Up-front	Deal summary
Voyager	Neurocrine	$136m*	Rights to Voyager’s GBA1 gene therapy for Parkinson’s disease & 3 gene therapies for rare CNS targets (follows previous deal over VY-AADC)
Trexbio	Lilly	$55m	Discovery of Treg-based therapeutics for immune-mediated diseases
Klinge	Coherus	€30m**	US rights to Klinge's FYB203, a biosimilar version of Eylea
Kronos	Roche	$20m	Use of Kronos's drug discovery tech against transcription factors selected by Roche
Autolus	Cabaletta	ND	Rights to Autolus’s RQR8 safety switch for use in autoimmune disease project
Recode	Askbio (Bayer)	ND	Discovery deal combining Askbio's synthetic DNA & gene-editing nucleases with Recode’s LNP tech
Notes: *plus $39m equity investment; **$32m; ND=not disclosed. Source: company releases. https://www.evaluate.com/vantage/articles/events/conferences-snippets/jp-morgan-2023-licensing-deal-flurry-offers-limited

Moderna: Advances Across mRNA Pipeline

COVID-19 vaccine sales for 2022 approximately $18.4 billion (unaudited)

Reiterating 2023 expected minimum COVID-19 vaccine sales of approximately $5.0 billion; continue to expect additional contracts for 2023

Company continues to scale with 48 programs in development, including 36 in ongoing clinical studies, and is increasing R&D investment to an expected $4.5 billion for 2023

Pivotal Phase 3 RSV study of mRNA-1345 in older adults (≥ 60 yrs.) has now accrued the cases required to complete our first interim efficacy analysis

Moderna and Merck announced mRNA-4157/V940, in combination with KEYTRUDA, demonstrated a 44% reduction in the risk of disease recurrence or death in melanoma patients. Phase 3 study in melanoma patients to start in 2023, with rapid expansion to additional tumor types

Phase 1/2, multiple ascending dose Paramount study of propionic acidemia (PA) candidate (mRNA-3927) is ongoing

https://finance.yahoo.com/news/moderna-announces-advances-across-mrna-120000769.html

Free access to Zolgensma curbed, says Novartis

 Novartis’ programme providing free access to its spinal muscular atrophy (SMA) gene therapy Zolgensma is being scaled back to a dozen countries worldwide, according to the company.

First introduced in 2020, the global Managed Access Programme (gMAP) has provided Zolgensma (onasemnogene abeparvovec) free of charge to nearly 300 children with the genetic disorder across 36 countries where the therapy has not yet received approval or in which no formal access pathway exists.

SMA is a genetic disorder that can cause rapid and irreversible loss of motor neurons, affecting muscle functions, including breathing, swallowing, and basic movement.

That comes to an end today, however, as Novartis is winnowing down the countries where the gMAP pathway will be available.  A spokesperson told pharmaphorum that from now onwards the programme will cover just 12 countries, namely: Colombia, India, Indonesia, Malaysia, Mexico, New Zealand, Philippines, Serbia, Singapore, Thailand, Uruguay, and Vietnam.

Since 2020, the global SMA treatment landscape has progressed, with three treatments now approved, according to Novartis.

Along with Zolgensma – which made its debut in 2019 – Biogen has had approval to market its antisense-based therapy Spinraza (nusinersen) since 2016, while Roche got a green light for its orally-administered therapy Evrysdi (risdiplam) in 2020.

Zolgensma, meanwhile, is now approved in 45 countries, with over 2,500 patients treated globally across clinical trials, managed access programmes, and in the commercial setting.

“With these advancements in mind, we are redefining the geographic scope of the [gMAP] to countries where it is currently possible to make Zolgensma available as a future long-term sustainable solution,” said Novartis in a statement on the changes, adding that they will “ultimately benefit more patients over time.”

Zolgensma is one of the most expensive therapies available, with a price tag of around $2.1 million in the US and just under €2 million in Europe, which the company says is justified by its dramatic benefits when given as a one-shot therapy to patients with SMA.

Novartis has been working hard to encourage screening of newborns for the SMN1 gene mutation that causes SMA, in order to allow treatment to be carried out as early as possible, when they have the greatest chance of normalising their development.

“We recognise this decision will be disappointing to patient families in countries no longer eligible,” said Novartis, which pledged to “honour our commitment” to patients already enrolled who will continue in the programme as long as they remain medically eligible.

Pause in UK access

Meanwhile, access to Zolgensma in the UK has been suspended in children older than 12 completed months, as there have been a “small number” of cases of liver-related side effects among children who “are older and weighing more than 13.5 kg.”

NHS England said the temporary change in eligibility – which ties in with NICE guidance – has been implemented, as there are two other disease-modifying drugs available on the NHS for the treatment of SMA.

https://pharmaphorum.com/news/free-access-to-zolgensma-curbed-says-novartis/

Novartis licenses cocaine use disorder therapy to Stalicla

 Swiss biotech Stalicla has continued to diversify its pipeline from a focus on autism therapies with a deal to license Novartis’ mavoglurant, in clinical trials for cocaine use disorder (CUD) as well as neurodevelopmental disorders (NDD).

Geneva-based Stalicla has acquired worldwide rights to mavoglurant (also known as AFQ056) across all its potential indications for an undisclosed upfront fee and equity, and up to $270 million in development and commercial milestone payments.

The twice-daily oral therapy is a metabotropic glutamate receptor 5 (mGluR5) antagonist that has been shown in a phase 2 trial to help cocaine users abstain from using the drug without suffering withdrawal symptoms, and is poised to start a phase 3 programme.

It also has potential in NDD, although it was discontinued as a treatment of fragile X syndrome in 2014 after disappointing phase 2b trial results. Novartis paused development across all its potential indications three years later, citing more pressing priorities in its pipeline – so, Stalicla’s licensing deal has resurrected a dormant programme.

Stalicla said it will use its precision neurobiology drug development platform (DEPI), which has demonstrated proof-of-concept in other neurodevelopmental programmes, to detect subgroups of patients with NDDs who are likely to respond to mavoglurant treatment.

The market potential of the CUD and NDD indications alone could top 2 billion euros ($2.12 billion) globally, the company noted.

“Stalicla stratifies patient subgroups and identifies compounds that may provide medical benefit in neurodevelopmental indications with clear unmet need,” said its founder and chief executive, Lynn Durham.

“With two phase 2 and a phase 3 trial slated to start within a year, alongside strong IP, we are well positioned to continue our exciting growth trajectory,” she added.

The Swiss biotech’s current pipeline is headed by autism spectrum disorder (ASD) therapies STP-1 (ibudilast/bumetanide) and STP-2 (stabilized, synthetic sulforaphane), which are due to start phase 2 testing this year. STP-2 was licensed from Evgen Pharma in October last year.

In 2020, Roche offloaded an mGluR5 antagonist to Swiss start-up Noema, which is developing the drug for persistent seizures in tuberous sclerosis complex and severe pain in trigeminal neuralgia.

https://pharmaphorum.com/news/novartis-licenses-cocaine-use-disorder-therapy-to-stalicla/

Raymond James Raises Ventas (NYSE:VTR) Price Target to $55

 Ventas (NYSE:VTR - Get Rating) had its target price upped by investment analysts at Raymond James from $46.00 to $55.00 in a research note issued on Monday, The Fly reports. Raymond James' price target would suggest a potential upside of 15.01% from the company's current price.

https://www.marketbeat.com/instant-alerts/nyse-vtr-a-buy-or-sell-right-now-2023-01/