Why Novo Nordisk should buy Uniqure

Instead of tinkering with early-stage genome editing deals like this week’s agreement with Bluebird, Novo Nordisk should make a decisive move in haemophilia.
Novo Nordisk’s tie-up this week in haemophilia genome editing was undoubtedly interesting, but a better move would be an outright acquisition of one of the haemophilia gene therapy players – and Uniqure fits the bill.
Early-stage deals will not solve one of Novo’s big problems. Unless it acts quickly the Danish company risks getting left behind in a core area while its diabetes business comes under increasing pressure.
And despite recent takeout speculation, Uniqure is not too pricey: with a market cap of around $1.8bn, Novo could expect to pay less than $3bn, even with a premium. The Danish company showed itself willing to spend this much with last year’s unsuccessful $3.1bn bid for Ablynx.
Best in haemophilia B?
Uniqure has what looks like the most promising haemophilia B gene therapy, AMT-061, with the caveat that this has only been tested in a small number of patients so far (Uniqure turns the screw on Spark and Pfizer, February 8, 2019).
What’s more, AMT-061 could become the first haemophilia B gene therapy to reach the market: the pivotal Hope-B trial reads out towards the end of next year. Meanwhile, the phase III study of Spark and Pfizer’s contender, fidanacogene elaparvovec, is not set to complete until 2021.
Haemophilia B is much rarer than haemophilia A, so is a smaller market. Nevertheless, EvaluatePharma sellside consensus puts AMT-061’s net present value at $1.5bn, which would go a long way towards justifying Uniqure’s price tag.
And there is a more pragmatic reason for Novo to prioritise haemophilia B over haemophilia A in deal-making: most of the main contenders in the latter are out of the Danish company’s reach. Biomarin has a market cap of $12bn, while Spark is being acquired by Roche, and Sangamo’s SB-525 is partnered with Pfizer.
Uniqure does have a haemophilia A project, AMT-180, at the preclinical stage. Although this would not assuage any concerns at Novo about missing the haemophilia A gene therapy boat, it could be an intriguing asset given its different approach. Unlike other haemophilia A gene therapies AMT-180 might work in patients who have developed inhibitors; Uniqure plans to file an IND for it next year.
Pipeline bonus
The rest of Uniqure’s pipeline would then be a bonus, although not all of it would make a good fit.
Assets in Fabry disease and other disorders with liver involvement could be attractive, but after AMT-061 Uniqure’s next most advanced asset is the Huntington’s candidate AMT-130, an area well outside Novo’s wheelhouse. The company could just sell the project on, further boosting the premium-priced takeout thesis.
Novo has previously said it is willing to strike more external deals, but so far these efforts have been limited to early-stage tie-ups. It is time to take a bigger gamble.

Uniqure’s pipeline
				Annual sales ($m)
Project	Indication	Description	Status	2024e sales	Peak sales
AMT-061 (etranacogene dezaparvovec)	Haemophilia B	AAV5 FIX-Padua gene therapy	Phase III	744	1,229
AMT-130	Huntington’s disease	AAV5-delivered micro-RNA	PhI/II to start end-2019	69	2,686
AMT-180	Haemophilia A	AAV5 FIX-Super9 gene therapy	Preclinical	–	–
AMT-190	Fabry disease	AAV5 NAGA gene therapy	Preclinical	–	–
AMT-150	Spinocerebellar ataxia type 3	AAV5-delivered micro-RNA	Preclinical	–	–
Undisclosed liver and CNS-directed projects	–	–	Preclinical	–	–
Source: EvaluatePharma, company presentation Oct 2019.

https://www.evaluate.com/vantage/articles/analysis/vantage-views/why-novo-nordisk-should-buy-uniqure

FDA OKs Lilly’s lasmiditan for migraine

The FDA approves Eli Lilly’s (NYSE:LLY) REYVOW (lasmiditan) for the acute treatment of migraine, with or without aura.

Lasmiditan is an orally available 5-HT1F receptor agonist that blocks the pain transmission without the side effects of the class of migraine therapies called triptans. The 5-HT1F receptor is a serotonin subtype that lacks the vasoconstrictive properties of other serotonin receptors, which can cause adverse cardiac events in patients with cardiovascular or cerebrovascular disease.

The controlled substance classification is currently under DEA review. A human abuse potential study was done that showed less drug liking with therapeutic doses of lasmiditan than alprazolam (Pfizer’s Xanax). Once completed, the product will be available in retail pharmacies.

https://seekingalpha.com/news/3505358-fda-oks-lillys-lasmiditan-migraine

89bio on deck for IPO

89bio (ETNB) has filed a preliminary prospectus for a $70M IPO.

The San Francisco, CA-based biopharmaceutical firm develops therapies for liver and cardio-metabolic diseases. Lead candidate is BIO89-100, an engineered gycoPEGylated (drug works in the body longer) analog of fibroblast growth factor 21 (FGF21), for the potential treatment of nonalcoholic steatohepatitis (NASH). A Phase 1b/2 clinical trial launched in July with topline data expected in H2 2020.

2019 Financials (6 mo.)(comparison period is not exact since inception was 1/18/18): Operating Expenses: $8.8M (+27%); Net Loss: ($19.4M) (-162%); Cash Burn: ($8.1M) (-22%).

https://seekingalpha.com/news/3505364-89bio-deck-ipo

UnitedHealth gets another downgrade

UnitedHealth Group shares have been falling in recent weeks, and Jefferies analysts aren’t sure the trend will turn soon, according to Barron’s.
UnitedHealth shares are down 10.9 percent this year. On Oct. 10, Jefferies analyst David Windley downgraded UnitedHealth to “hold” from “buy,” according to a research note cited by Barron’s. Mr. Windley cut price targets for six other stocks, including competitors Anthem, Cigna and Humana.
BMO Capital Markets also downgraded UnitedHealth. Political uncertainty has fueled much of the poor performance in the S&P 500’s managed healthcare subindustry group this year. The group is down 19 percent since February, while the broader S&P is up 8 percent.
“MCO sentiment turned abruptly negative a year ago and has stubbornly remained there,” Mr. Windley wrote. “The primary poison in the punch bowl, political risk, won’t likely abate for at least another nine months.”
https://www.beckershospitalreview.com/payer-issues/unitedhealth-stocks-get-another-downgrade.html

Judge sees benefit in pausing lawsuits against OxyContin maker Purdue

A U.S. Bankruptcy Judge signaled support on Friday for a six-month pause to litigation led by 24 states against OxyContin maker Purdue Pharma LP to give the company time to settle thousands of lawsuits alleging it fueled a deadly nationwide opioid crisis.

U.S. Bankruptcy Judge Robert Drain in White Plains, New York, said there was little benefit from numerous states trying to prove at trial the liability of Purdue and its controlling Sacker family for improper marketing of opioids.
“A trial is at best a limited way to get to the truth,” said Drain, adding that verdicts often result in debates about the meaning of the outcome.
“There are trials where people stand up and say ‘I did it.’ But that mostly happens on Perry Mason,” he said, referring to the popular TV show from the 1950s and ‘60s featuring a lawyer who won virtually every case.
Drain was asked to pause for about six months more than 2,600 lawsuits against the privately-held company and controlling Sackler family for their part in the opioid crisis, which has led to some 400,000 deaths from 1999 to 2017, according to U.S. statistics.
The company filed for bankruptcy last month to build support for a proposed settlement that it values at more than $10 billion, and said the pause in litigation will preserve money spent on legal fees.

Most of the lawsuits were brought by local governments, and most back the deal, but at least 24 states oppose it.
Drain said the public deserves an accounting of the company’s role in the crisis, but he feared a “trial becomes an autopsy” that destroys the value of Purdue.
He suggested a court-ordered examiner could investigate the company and Sacklers, as was done in the bankruptcies of Enron Corp and Lehman Brothers.
The settlement proposes to transfer Purdue’s ownership from the Sacklers to a public trust owned by the plaintiffs. In addition, the family has also pledged to contribute at least $3 billion to the settlement.
Purdue’s lawyer Marshall Huebner spelled out an agreement struck on Friday morning between the company, the Sacklers and the official committee of unsecured creditors.
The creditors committee would be charged with vetting the proposed settlement and Purdue would provide millions of pages of documents. The Sacklers would provide an accounting of their wealth and would agree to refrain from taking any material action with their property.

The agreement does not bind the hold-out states, but Drain urged them to join the negotiations.
The hearing was still underway on Friday afternoon.
https://www.reuters.com/article/us-purdue-pharma-bankruptcy/judge-sees-benefit-in-pausing-lawsuits-against-oxycontin-maker-purdue-idUSKBN1WQ1FV

Horizon Therapeutics’ Phase 3 trial finds ‘significant benefit’ of teprotumumab

Horizon Therapeutics (HZNP +3%) reports new data from Phase 3 OPTIC confirmatory clinical trial that shows teprotumumab provided significant benefit on several effects of active thyroid eye disease — such as double vision, quality of life, and clinical activity score — vs. placebo.

Provides data on three secondary endpoints:

Patients receiving teprotumumab had a mean change of 13.79 on the Graves’ Ophthalmopathy Quality of Life (GO-QoL) scale compared with a change of 4.43 for patients receiving placebo (p<0.001); scores indicate a statistical and clinically meaningful improvement over placebo in these QoL measures.

At week 24, 68% of patients receiving teprotumumab had an improvement from baseline of at least one grade in diplopia (double vision), compared to 29% of patients receiving placebo (p=0.001).

At week 24, more patients achieved a CAS value of 0 (which indicates no swelling or activity) or 1 with teprotumumab treatment (59% vs 21% of placebo participants) (p<0.001).

https://seekingalpha.com/news/3505317-horizon-therapeutics-phase-3-trial-finds-significant-benefit-teprotumumab

Walmart Adds Kidney Transplants At Mayo To Centers Of Excellence Program

Walmart is adding kidney transplants to the list of specialized medical procedures it will cover for its workers under its now 22-year-old Centers of Excellence Program for organ transplantation.

The world’s largest retailer in 1997 began its Centers of Excellence program as a way to get organ transplants to workers in need. In a conference call Wednesday with employers put on by the Catalyst for Payment Reform, Lisa Woods, Walmart’s senior director of U.S. healthcare, said centers of excellence would be performing kidney transplants as a covered benefit starting in 2020. The transplant locations are Mayo Clinic sites in Rochester, Minn.; Phoenix, Ariz. and Jacksonville, Fla. where Walmart already sends patients for other transplant procedures and certain other treatments in Walmart’s broader Centers of Excellence program.
“As one transplant center with three locations, we are in a unique position to serve Walmart’s beneficiaries,” said Dr. Carrie Schinstock, Mayo’s medical director of Kidney Transplantation. “All of our patients benefit from our innovative approaches which include kidney donor chains, maximizing use of all donated organs, and performing kidney transplants before patients go on dialysis – all of which lead to more transplants with better outcomes.”

Catalyst for Payment Reform is a nonprofit working with employers and other purchasers of medical care to coax the U.S. healthcare system into offering more value for the dollars they are spending. Walmart was discussing its various healthcare programs it is launching next year for its employees and large employers are watching these efforts closely, those on the call said.
Since 2012, the centers of excellence program has been greatly expanded beyond transplants and was given the more formal name “Walmart Centers of Excellence,” offering the retailer’s workers specialized treatments for cancer, organ transplantation, spine and heart surgeries at sites across the country. Walmart now has 16 Centers of Excellence health systems nationwide across all programs combined offering workers treatments for cancer, organ transplantation, joint replacement, spine and heart surgeries at sites that include the Mayo Clinic, Cleveland Clinic, Geisinger Health System and Johns Hopkins.

Under Walmart’s Centers of Excellence Program, the retailer sends employee patients to designated sites to better ensure they are getting treatment that is done right the first time to improve quality and keep the employee healthy and working. If they are sent to a Center of Excellence, “travel, lodging and a daily allowance will be provided for the recipient and a caregiver for all services covered under the Centers of Excellence program,” Walmart said.
“We are able to coordinate patient care and waiting list management across our three locations so that patients can receive a transplant sooner than would otherwise be possible,” said Dr. Charles Rosen, a transplant surgeon and Medical Director of Contracting and Payor Relations at Mayo Clinic.
Today, Walmart’s two-decade old transplantation program has been followed with 88% using some kind of Center of Excellence whether it be for transplantation, heart surgery, spinal or joint replacement, according to National Business Group on Health’s 2019 Large Employers’ Health Care Strategy and Plan Design Survey of about 170 large U.S. employers.
The addition of the transplant network to the Walmart Center of Excellence program is only the latest effort the retailer is gaining converts to among policymakers and employers.
“Quality of care in the U.S. varies significantly,” said Catalyst for Payment Reform executive director Suzanne Delbanco. “Walmart is setting the pace for employers by pioneering new ways of connecting employees to the highest quality providers to ensure they get the right care, delivered in the right way, and in the right setting.”
https://www.forbes.com/sites/brucejapsen/2019/10/10/walmart-adds-kidney-transplants-at-mayo-to-centers-of-excellence-program/#274c38eb4143