White House: Call for vaccine 'mandate' is 'misinformation'

 White House Deputy Press Secretary Karine Jean-Pierre on Friday said that it’s “misinformation” to use the term “vaccine mandate” to describe a requirement that most private-sector workers get vaccinated, submit to regular testing or lose their jobs.

She referred to it instead as a “vaccination requirement.”

The policy, set to take effect Jan. 4, compels workplaces with 100 or more staff to impose a COVID-19 vaccine mandate or a policy that allows unvaccinated staff to keep their jobs if they submit to weekly testing and wear masks at work.

But 26 Republican-led states are suing to halt the mandate, which is estimated to cover about 84 million of the 161 million people who are in the US labor force.

“As for the legal side of this, let me be crystal clear to avoid what appears to be possible misinformation or disinformation around the emergency temporary standard being a ‘vaccine mandate.’ That would be on its face incorrect,” Jean-Pierre said at the daily White House press briefing.

President Biden announced the vaccine rules on Nov. 4. The policy is set to take effect on Jan. 4, 2022.

AFP via Getty Images

“As has been explicit for months, it is a standard for safe workplaces to either comply with weekly testing or to be vaccinated. And second, as outlined the Department of Labor has a responsibility to keep workers safe and the legal authority to do so.”

The private-sector mandate is scheduled to take effect the same day as two other Biden vaccine mandates impacting federal contractors and about 17 million health care workers, with certain medical and religious exemptions.

There’s a Dec. 8 compliance deadline for people employed directly by the federal government.

Despite the Biden administrations efforts, 26 Republican states are suing to halt the mandate. On Nov. 5, House Republicans and former OMB Director Russ Vought (center) speak out against the new policy at Capitol Hill.

Lenin Nolly/SOPA Images/Shutters

At the Friday briefing, Jean-Pierre also was asked about Green Bay Packers quarterback Aaron Rodgers admitting he was unvaccinated and dissing the “woke” advocates for vaccination, but she said that “no” the White House wasn’t worried about its vaccine messaging.

“If you look at the vaccination requirement, it would cover 100 million American workers. That’s how we’re going to get to the other side of this,” she said.

Later in the briefing, Jean-Pierre said that “herd immunity” was no longer a near-term Biden administration goal. US health officials initially believed that perhaps 70 percent of people being vaccinated would end the pandemic, but the more contagious Delta variant of COVID-19 upended what had seemed an achievable goal.

According to CDC data, 80.4 percent of US adults have had at least one COVID-19 vaccine shot — as have 78.5 percent of people older than 12 and 67.1 percent of the total US population.

Jean-Pierre also confirmed that “herd immunity” was no longer a near-term goal for the Biden administration.

REUTERS

Asked about the current estimate for the percentage of Americans who must be vaccinated, Jean-Pierre said it was “not our focus.”

“I understand your question and I get it. I get wanting to get a sense of the herd immunity. But that is not our focus right now. Our focus is to make sure that we do everything we can to get people vaccinated,” Jean-Pierre said.

“Now we have 5-11 — young kids from 5-11 — who can now get vaccinated, which is incredibly important… Having these vaccine requirements, that’s very important. I just mentioned, 100 million workers… that’s what that requirement is going to touch, 100 million workers.”

https://nypost.com/2021/11/05/white-house-calling-vaccine-policy-mandate-is-misinformation/

With ACIP recommendation, is Dynavax set to win the hepatitis B sweepstakes with Heplisav-B?

 A CDC advisory committee on Wednesday strengthened its recommendations for hepatitis B vaccination, and that's likely to flood the market with people seeking shots. Among the three approved vaccines, Dynavax’s Heplisav-B is poised to take the most advantage, said analysts at Evercore ISI.

“Heplisav-B already is positioned to be the standard of care, given its greater efficacy and two-dose schedule,” Evercore wrote in a note to investors.

While Dynavax's two doses are given a month apart, the other vaccines on the market, GlaxoSmithKline’s Engerix-B and Merck’s Recombivax HB, are generally administered in three doses over a six-month span.

Evercore believes the CDC's latest recommendation will expand the hepatitis B market by 50% to $600 million, “significantly accelerating Heplisav-B sales in the coming quarters.” During Dynavax’s third-quarter earnings presentation on Thursday, the California-based company estimated the hepatitis B vaccine market at $800 million.

Sales for Heplisav-B came in at $22.7 million, the most in a quarter since its launch in 2018 and accounting for more than one-fifth of the 25-year-old company’s revenue of $108.3 million for the period.

While CDC's prior guidance noted that all adults "may" get a vaccine, its recommendation for those who "should" receive it was focused only on adults deemed at a high risk. With this week's 15-0 CDC panel vote, all those between 19 and 59 years, regardless of risk factors, are now included in the category of those who should get the vaccine. Those who are 60 years and older who are at risk should also get the vaccine, the panelists said. Other adults who want to get vaccinated remain eligible as well.  

After failed attempts to gain approval in 2013 and 2016, Heplisav-B finally prevailed in November 2017, setting it up to take on Engerix, the dominant shot for hepatitis B since it was approved in 1989. 

“Heplisav-B provides an important foundation for our company as our lead commercial asset, generating durable, long-term revenue growth,” Dynavax CEO Ryan Spencer said in a conference call.

Most U.S. residents 30 and younger have been vaccinated for hepatitis B, as it was established in 1991 as standard practice. In 2005, it was recommended that newborns be vaccinated for hepatitis B before discharge from the hospital.

Engerix and Recombivax have adult and pediatric formulations, while Heplisav is designed solely for people 18 and older.

Wednesday’s recommendation from the Advisory Committee on Immunization Practices is subject to final approval by CDC director Rochelle Walensky.

The CDC recommendation defines those with risk factors as incarcerated people, those at high risk for infection, people who travel to places with endemic HBV, those who have chronic liver disease and people who have HIV.

It is estimated that 2 million people living in the U.S. have chronic hepatitis B and have a 15% to 25% risk of premature death from cirrhosis or liver cancer. There are approximately 20,000 new cases every year, and the rate has stopped declining.

“The past decade has illustrated that risk-based screening among adults has got us as far as it can take us,” Mark Weng, M.D., who leads the ACIP working group, said. “We’re losing ground. We cannot eliminate hepatitis B in the U.S. without a new approach.”

The virus is spread through the exchange of bodily fluids like blood and semen. Many cases have been linked to the opioid epidemic.

The Hepatitis B Foundation applauded the ACIP's recommendation.

“It has been frustrating to watch rates of infection rise when we know that there is a safe and effective vaccine that can prevent hepatitis B and liver cancer," said the foundation's Michaela Jackson in a statement. "This recommendation will help remedy a very significant health inequity for marginalized groups and it will serve to make many adults in the U.S. safer.”

https://www.fiercepharma.com/pharma/acip-recommendation-tiny-dynavax-set-to-win-hepatitis-b-sweepstakes-heplisav-b

Democrats' drug pricing deal is 'not a bad outcome' for pharma, analysts write

 After intense debate over the last few weeks, Democratic leaders appear to have landed on a framework for a drug pricing deal. The pharmaceutical industry has strongly resisted some of the proposals presented in the years-long drug pricing brouhaha, and the final result is "not a bad outcome" for drugmakers, one team of analysts recently stated. 

The deal includes partial Medicare Part B and D negotiations, which Evercore ISI analysts called "negotiation in name only." The "practical way to think" about this component of the deal, the analysts wrote to clients Friday, is that drugs on the market for five to 12 years will get a 25% discount in Medicare. Medicines six to 12 years old will get a 35% discount, and a higher discount will apply to older drugs. There's a steep tax for dodging the negotiation process, the analysts wrote.

But not all drugs will be eligible for negotiations. The process starts with the "10 most costly Medicare drugs in 2025," then climbs to 15 medicines in 2026 and 2027 and to 20 medicines in 2028 and beyond. That means the majority of Medicare drugs won't be affected by the negotiation component, the team wrote.

The deal also implements price hike caps starting in 2023, the analysts wrote. This key portion of the deal will cap price hikes at the rate of inflation, and the rule applies to commercial insurance coverage as well. Companies that hike prices beyond inflation rates "will owe the dollars back to the government."

"We think this could incentivize drugmakers to inflate launch price," the analysts wrote in a note.

The drug pricing deal also calls for a $2,000 out-of-pocket cap for Medicare patients and a $35-per-month price maximum for insulin, according to reports. 

In all, considering the drug pricing conversations started with universal Medicare negotiations and featured proposals such as international reference pricing, the deal is "not a bad outcome" for the industry, the Evercore ISI team wrote.

"It looks the deal is in good shape to be consummated before year-end with few changes expected," the team wrote. "It has broad support across legislators and industry. Our Washington team doesn’t anticipate much pushback on the drug pricing component of the larger bill."

If it makes its way into law, the bill would cap a years-long push to reign in drug prices by governments of both major political parties.

https://www.fiercepharma.com/pharma/democrats-drug-pricing-deal-not-a-bad-outcome-for-pharma-analysts-write

Deciphera’s pipe dream dies

 Moving into early lines of therapy was financially crucial for Deciphera’s Qinlock, but this possibility now looks to be off the table. The Intrigue study failed to show a PFS benefit with Qinlock over Sutent in second-line gastrointestinal stromal tumours, news that knocked $1.5bn, or 75%, off Deciphera’s market cap this morning. In fourth-line disease Qinlock is the standard of care, but in US sales have plateaued and just $21.7m was recorded in the third quarter. A fourth-line approval decision in Europe, due this quarter, will provide little solace. Consensus had pencilled in $1.2bn by 2026, according to Evaluate Pharma, a figure now set for some substantial downgrades. Stifel now sees peak sales of a mere $200m, which assumes that ex-US use will ramp to match US sales. Deciphera is to review the remainder of its pipeline; two novel projects that have attracted minimal investor interest so far are about to enter phase 3. These trials must now be be funded with cash reserves rather than revenue stream, Stifel points out. It could be some time before the company gets investors back on board.

Deciphera's limited pipeline
Status	Project	Mechanism	Note	Annual 2026 sales $m
Marketed	Qinlock	Platelet-derived growth factor receptor antagonist; Proto-oncogene c-Kit inhibitor	Sold in US for 4L GIST, EU approval decision Q4; 2L Intrigue study failed; ph1/2 plus Mektovi, Nov start date	1,177*
Ph 3	Vimseltinib (DCC-3014)	Macrophage colony stimulating factor receptor 1 inhibitor	Motion study set to start Q4 in tenosynovial giant cell tumour	114
Ph 2	Rebastinib	Bcr/Abl fusion protein inhibitor; Tunica interna endothelial cell kinase 2 inhibitor	Ph3 due to start 2022, + paclitaxel in platinum-resistant ovarian cancer	119
Ph 1	DCC-3116	Serine/threonine-protein kinase ULK2 inhibitor	Initial dose-escalation data due 2022, +/- Mekinist, advanced or metastatic solid tumours with Ras or Raf mutations	-
*Consensus before Intrigue failure. Source: Evaluate Pharma, clinicaltrials.gov & company releases. https://www.evaluate.com/vantage/articles/news/snippets/decipheras-pipe-dream-dies

Move over molnupiravir, here comes Pfizer’s Paxlovid for Covid

 A good week for Pfizer’s Covid-19 efforts has ended with topline data on its antiviral that could not look much better. Paxlovid, as PF-07321332 is now called, generated an 89% reduction in the risk of hospitalisation or death versus placebo in patients at high risk of severe disease who were treated at home. The results are from an interim analysis of the now-halted phase 2/3 Epic-HR trial. That risk reduction figure is derived from patients treated within three days of symptom onset, the study’s primary endpoint. Only three of 389 Paxlovid-treated subjects were hospitalised, versus 27 of 385 in the placebo arm, generating a highly statistically difference (p<0.0001). Similarly impressive reductions were seen in patients treated at five days and, in what will surely mean a swift emergency use authorisation, no deaths were reported in the Paxlovid arm through day 28, against 10 in the placebo group. Comparing across trials is never ideal, though the result seems easily to beat the 50% reduction generated by Merck & Co and Ridgeback’s molnupiravir in the similar Move-Out trial. Little wonder that Pfizer opened 10% higher today, while Merck shares dropped a similar amount.

Paxlovid's late-stage clinical programme
Trial	Setting	Results
Epic-HR	Non-hospitalised adults at high risk of severe illness	Initiated in Jul 2021; 89% risk reduction vs placebo at interim analysis at 70% enrolment; almost half of subjects US-based
Epic-SR	Non-hospitalised adults at low risk of severe illness	Ongoing; initiated in Aug 2021
Epic-PEP	Post-exposure prophylaxis, adults with household contacts	Ongoing; initiated in Sep 2021
Note: Paxlovid is a co-administration of PF-07321332 with low dose ritonavir; the latter helps slow the metabolism of the former. Source: company statements. https://www.evaluate.com/vantage/articles/news/snippets/move-over-molnupiravir-here-comes-pfizers-paxlovid-covid

What Novartis could buy with its windfall

 Novartis’s sale of its stake in Roche, announced today, means the group will soon have $20.7bn burning a hole in its pocket. And there could be more to come, if Novartis sells Sandoz – something that looks on the cards after it recently started a strategic review of the generic business.

There are reasons why Novartis might be looking to strike big. A string of smaller buyouts have disappointed, and its pipeline contains few inspiring projects. The company claims to be looking at bolt-ons but it would hardly advertise its desperation by spelling out its specific targets. So, what could Novartis buy with the cash?

Takeout talk is currently swirling around the lupus player Aurinia, with both Bristol Myers Squibb and Glaxosmithkline said to be interested, although the latter dismissed such reports this week. Aurinia could also be a fit for Novartis, a big player in the autoimmune space; however, given the size of its war chest, the Swiss group could have its eye on bigger targets.

Jefferies mooted oncology, cardiovascular and perhaps novel gene technologies as potential areas for Novartis deals.

In oncology, the likes of Exelixis or Incyte could be safe if unexciting bets. Both have approved drugs but have struggled with becoming commercial entities; these groups' products could benefit from being in the hands of a bigger player. Incyte, with which Novartis is already partnered, is sitting at close to five-year lows.

Going bigger?

If Novartis is prepared to splash a bit more cash it could get its hands on Alnylam, which also has several marketed products to its name. Still, that group looks expensive at nearly $21bn, and its rival Arrowhead Pharmaceuticals would be a cheaper move into this space. A takeout of the latter would be an interesting turn of events, considering Arrowhead bought its RNAi tech from Novartis for $35m in 2015.

However, Novartis might have been burned by its experience in RNAi with inclisiran, gained through its $10bn purchase of the Medicines Company.

Also in the $20-30bn bracket is Eisai. This would be a leftfield move but could give Novartis – which already has a presence in neuroscience through its MS drugs – entry into the lucrative Alzheimer’s space. Buyouts of Japanese groups by western suitors rarely happen, however.

Splashing the cash? What Novartis could get with its Roche windfall
Company	Area	Market cap
Exelixis	Oncology	$6.1bn
Arrowhead	RNAi therapeutics	$8.4bn
Incyte	Oncology	$14.8bn
Alnylam	RNAi therapeutics	$20.7bn
Eisai	Neuroscience	$21.1bn
Horizon Therapeutics	Autoimmune/inflammatory	$26.3bn
Seagen	Oncology	$32.8bn
Vertex	Cystic fibrosis & rare diseases	$49.1bn
Note: Market cap at close on November 3, 2021. Source: Evaluate Pharma.

Others in this price range include Horizon and Genmab – the last might be an attractive way into cancer antibodies, but it hard to see how Novartis could make a swoop here given Genmab’s ties with Johnson & Johnson.

Horizon, which has presided over a strong launch of its thyroid eye disease drug Tepezza, might be a better fit, given Novartis’s existing presence in both autoimmune disease and ophthalmology via Xiidra and Beovu. 

Meanwhile, Seagen would give Novartis a revenue stream plus a new technology avenue in the form of antibody-drug conjugates. Both Horizon and Seagen are riding high on the stock market, but they are still well within the affordable range.

Even so, perhaps Novartis would be better off plumping for a group that is currently out of favour with investors but still has a lot to give. Step forward Vertex. The cystic fibrosis leader is currently valued at $49bn, less than the net present value of its marketed products alone, according to Evaluate Omnium.

Purchasing Vertex would also give Novartis a stake in Crispr Therapeutics’ sickle cell disease project CTX001. Given Novartis’s interest in the likes of Car-T and gene therapy, gene editing must also be on its radar.

Given the group’s recent track record with smaller buys, it is surely time to go big or go home.

https://www.evaluate.com/vantage/articles/news/deals/what-novartis-could-buy-its-windfall

Sangamo takes on 4D in Fabry

 Another week, another early cut on a gene therapy for Fabry disease. This time it is Sangamo’s turn, with ST-920, also called isaralgagene civaparvovec, which showed promise in the first four patients in the phase 1/2 Staar trial. Two dose levels, 0.5x1013 and 1x1013vg/kg, caused alpha-galactosidase A (AGA) activity of two-fold to 15-fold above mean normal; AGA is the enzyme missing in Fabry patients. This is encouraging, but falls short of the 25-fold and 21-fold of normal levels shown last week in two of three patients treated with 4D Molecular Therapeutics’ 4D-310. But there were signs that the efficacy of 4D’s gene therapy diminished over time; this does not appear to be an issue with Sangamo’s project, with one patient maintaining AGA activity for an entire year. One potentially confounding factor is that the two patients in Staar with the highest levels of AGA were on enzyme replacement therapy, though Sangamo stated that only data from ERT trough sample collections were included. Safety was clear, with no liver enzyme elevations requiring steroid treatment and no serious treatment-related adverse events. Despite Staar’s protocol calling for the recruitment of more than 40 other patients, Sangamo is already planning phase 3 trials. 

Source: Company presentation.

https://www.evaluate.com/vantage/articles/news/snippets/sangamo-takes-4d-fabry