Prothena revives amyloidosis program nearly 3 years after flop

 Prothena canned its AL amyloidosis program in 2018 after it failed a midstage trial and a data monitoring committee deemed a separate phase 3 study doomed to fail. Now, the biotech is resurrecting the program after an analysis of the phase 3 data found the drug helped the sickest patients live longer.

That study, dubbed VITAL, tested the drug, known as birtamimab or NEOD001, against the standard of care in 269 patients with AL amyloidosis, short for amyloid light-chain amyloidosis. After terminating the study for futility, Prothena crunched the data and found that the sickest patients—those whose disease was classed as Mayo stage 4 at the start of the study—did significantly better on birtamimab than on placebo.

At the nine-month mark, the analysis found nearly three-quarters of the sickest patients on birtamimab were still alive compared to about half of the sickest patients taking placebo (74% versus 49%). Granted, these numbers are from just 77 patients, or 30% of the total patients in the trial, but they’ve convinced Prothena and the FDA that there is a future for this drug in these patients.

Under a Special Protocol Assessment agreement with the FDA, Prothena company will kick off a new phase 3 study in mid-2021. It will test the drug, known as birtamimab or NEOD001, in patients with Mayo stage 4 AL amyloidosis. The disease is similar to multiple myeloma in that it stems from dysfunctional plasma cells in the bone marrow. They produce an abnormal version of light chain, a protein that makes up antibodies.

“The normal job of immunoglobulin light chain is to combine with heavy chain to make immunoglobulins, or antibodies,” said Prothena CEO Gene Kinney, Ph.D. The abnormal light chain proteins don’t bind properly with the heavy chain proteins, fold incorrectly and build up in various tissues, most notably in the heart. Over time, this buildup can lead to life-threatening problems, including heart and kidney failure.

“When we talk about Stage IV patients—if we look to the literature—the predicted median survival of those patients is somewhere around six months following diagnosis,” Kinney said.

The standard of care includes chemotherapy and cell-killing drugs that were originally developed for multiple myeloma. These treatments focus on eliminating abnormal plasma cells and reducing the amount of disease-causing protein they produce.

“The limitation is probably obvious for patients who already have an appreciable amount of protein deposition in vital organs,” Kinney said. “It’s essentially turning off the faucet once the bathtub is full.”

Prothena hopes that adding its drug to those already in use will help the sickest patients recover organ function and live longer.

The new phase 3 study, known as AFFIRM-AL, will test birtamimab in 260 patients with AL amyloidosis affecting their heart and who have never been treated. Two-thirds of the patients will receive birtamimab, while the remaining third will receive the standard of care. The primary endpoint is death from any cause. The plan is to conduct an interim analysis when about half of the patients in the study have died, at which point an independent data monitoring committee will recommend it either continue or be stopped for overwhelming efficacy, the company said in a statement.

https://www.fiercebiotech.com/biotech/prothena-revives-amyloidosis-program-nearly-3-years-after-flop

CDMO Catalent trumpets biologics windfall courtesy of COVID-19

 The COVID-19 pandemic has taken a toll on top lines throughout the biopharma industry—but not for New Jersey-based CDMO Catalent,

Instead, the pandemic has been a growth "accelerator," CEO John Chiminski said Tuesday on his company's second-quarter earnings call. With more than 80 pandemic projects under Catalent's belt, he's not kidding. Virus-related drug and vaccine products have given a massive boost to the company's biologics business, and with more shot capacity on the way, Catalent's COVID-19 work shows no signs of slowing down any time soon.

Buoyed by production contracts with major COVID vaccine players Moderna, Johnson & Johnson and AstraZeneca, Catalent saw its biologics revenues hit $403.9 million in the second quarter of its 2021 fiscal year. That's a whopping 76% increase in constant currencies over the same quarter last year.

All told, biologics made up 44% of Catalent's total net revenue for the quarter, which ended December 31, 2020. Taking acquisitions out the equation, net revenues for the company's biologics unit—on deck to crank out pandemic vaccines as well as therapeutics—jumped 65%, while profits for the segment climbed 104% versus the same period in 2019. 

That boost comes courtesy of the company's vast network of COVID-19 manufacturing partners, CEO Chiminski said on a call with analysts. Two of Catalent's vaccine partners—AstraZeneca and Moderna—are already rolling out vaccines to the public, and the CDMO is on deck to manufacture Johnson & Johnson's shot in the U.S., too.

J&J just last week unveiled long-awaited phase 3 data on its single-dose vaccine, showing it was 66% effective overall in global phase 3 trials, with efficacy climbing to 85% in severe disease. 

To match the pandemic's breakneck speed, Catalent has hustled along a number of planned capacity expansions in Europe and the U.S., Chiminski explained. With new filling lines on the way, the company figures it can meet demand for COVID-19 vaccines from its trio of partners and fill out its non-pandemic customer orders without disruption, he said. 

The company recently completed the buildout of a high-speed filling line, plus other capacity expansions, at its Bloomington, Indiana, plant—where the company is producing Moderna and J&J's vaccines. Its team there is now working 24/7 to meet U.S. demand, Chiminski said. 

All told, the company is on track to produce 100 million Moderna doses for the U.S. by March, out of a total 200 million doses it figures it can deliver by the end of June. 

Another high-speed filling line in Bloomington, first announced in 2020, is set to come online in the fourth quarter of the company's 2021 fiscal year. That line will be devoted to the production of Moderna's shot, among other products, Chiminski said. 

Plus, the company is establishing a high-speed flexible syringe cartridge filling line in Bloomington, too. That project won't be used for COVID-19 work, so the company is eyeing completion in the back half of 2021, Chiminski said.  

Those upgrades come in addition to new manufacturing trains being added to Catalent's cell manufacturing facility in Madison, Wisconsin; plans to boost capacity in Anagni, Italy; and a fill-finish facility in Limoge, France, that the company expects to complete this year, Chiminski said. 

During the call, analysts pressed the company about whether the U.S. government could order Catalent to prioritize production of COVID-19 vaccines through the Defense Production Act—a move that caused issues for drugmaker Horizon Therapeutics late last year when Catalent was forced to divert manufacturing slots for thyroid eye disease med Tepezza in favor of pandemic products. 

The short answer is no, Chiminski said. With a new high-speed filling line in place in Bloomington and another on the way, the company says it's equipped to meet capacity for government-mandated production as well as non-COVID orders. 

Overall, the company raked in $910.8 million in second-quarter revenues, up 24% in constant currencies from the $721.4 million reported for the same quarter last year. Armed with a slew of successful COVID-19 contracts, the company has raised full-year guidance to a range of $3.8 billion to $3.9 billion, up from its earlier projection of $3.5 billion to $3.7 billion. 

https://www.fiercepharma.com/manufacturing/cdmo-catalent-trumpets-76-biologics-revenue-boost-courtesy-covid-19

Pfizer's new rare-disease meds reach blockbuster stage despite pandemic hurdles

 While the COVID-19 pandemic dominated headlines at Pfizer and beyond last year, behind the scenes, the company has been busy with its launch of rare heart disease meds Vyndaqel and Vyndamax. And those efforts are showing. 

Vyndaqel and Vyndamax, approved in May 2019 to treat cardiomyopathy caused by transthyretin mediated amyloidosis (ATTR-CM), passed the blockbuster threshold in their first full year on the market as the company has been working to raise awareness of the disease and boost diagnosis rates. In 2020, despite challenges from the pandemic, the meds generated $1.3 billion, up from $473 million the prior year. 

At the end of last year, the diagnosis rate among ATTR-CM patients was 21%, Pfizer CEO Albert Bourla said on Pfizer’s fourth-quarter earnings call on Tuesday. That compares with 2% from when the drugmaker launched its medicines, which carry list prices of $225,000 per year. 

At the end of 2020, more than 20,000 patients had been diagnosed, and 8,500 had received Pfizer's drugs, Bourla said, including some who received them at no cost. After COVID-19 shutdowns affected patient-doctor visits last year, Pfizer has seen an improvement in diagnosis rates since the third quarter, Bourla said—though the resurgence of COVID-19 cases might affect that recovery, he cautioned.

Aside from the rare-disease meds, several of Pfizer’s other growth products “contributed significantly” to the company’s performance last year, Bourla said. Revenues for blood thinner Eliquis jumped 17% to $4.95 billion, while biosimilar revenues jumped 68% to $1.53 billion. Cancer therapies Xtandi and Inlyta and anti-inflammatory agent Xeljanz all chipped in to growth, too. In all, Pfizer's sales swelled 8% last year to $41.9 billion.

For its part, Prevnar 13—the company’s pneumoccocal vaccine and best-selling product—benefitted outside of the U.S. as the pandemic drove vaccine awareness. The shot’s sales grew 11% outside the U.S. 

Meanwhile, thanks to Pfizer's move last year to spin off its Upjohn business—which it combined with Mylan to form standalone company Viatris—the pharma giant's “decade-long conversion into a pure-play" science-based company is now complete, Bourla said in a statement. 

It's that effort that enabled the company’s quick success with its BioNTech-partnered COVID-19 vaccine program, which will be a major focus for Pfizer looking forward. The company expects $15 billion in sales from the shot this year, and it’s focused on producing 2 billion doses with manufacturing partners. 

https://www.fiercepharma.com/pharma/pfizer-s-vyndaqel-vyndamax-reach-blockbuster-threshold-despite-pandemic-s-challenges

Pfizer to deliver 200M Covid vax shots to U.S. by May, sooner than expected

 Pfizer plans to deliver 200 million doses of its coronavirus vaccine to the U.S. by May, earlier than its initial forecast of July, according to slides published Tuesday by the drugmaker ahead of its fourth-quarter earnings call.

The company, which developed its vaccine with German drugmaker BioNTech, also said it can potentially deliver 2 billion doses globally by the end of this year now that health-care providers can extract an additional sixth dose of the vaccine from the vials. In December, the Food and Drug Administration said extra doses from vials can be used after doses were being thrown away due to labeling confusion.

Pfizer had delivered 29 million doses of its two-shot vaccine to the U.S. government as of Jan. 31, according to the company. As of Monday, 17 million of those Pfizer doses have been administered, according to the Centers for Disease Control and Prevention.

The company’s Covid-19 vaccine was the first approved for emergency use in the U.S.

Pfizer, like other coronavirus vaccine makers, has been struggling to meet the demand for shots that hopefully will help bring an end to the pandemic. It recently enlisted the help of French drugmaker Sanofi to help produce 100 million doses of its vaccine.

The update on its supply timeline comes hours after Pfizer said it expects to sell about $15 billion in coronavirus vaccine doses this year. The company also raised its full-year earnings guidance to between $3.10 and $3.20 from $3 and $ 3.10, citing “additional refinements” of its vaccine revenue forecast.

The company also said Tuesday it is “prepared to respond” if a Covid variant demonstrates evidence that it is resistant to its vaccine. In recent weeks, U.S. health officials, including Dr. Anthony Fauci, have said they are concerned that vaccines currently on the market may not be as effective in guarding against new, more contagious strains of the virus.

In the slides published, Pfizer said patients will “likely need to boost regularly to maintain immune response and to counter emerging variant strains.”

https://www.cnbc.com/2021/02/02/covid-vaccine-pfizer-plans-to-deliver-200-million-doses-to-us-by-may-sooner-than-expected.html

US FDA approval tracker: January

 The first month of 2021 saw the approval of Aurinia’s Lupkynis, one of the most valuable launches of the year, according to sellside sales forecasts. The drug, indicated for use in lupus nephritis, is Aurinia’s sole product, and with approval in the bag some believe that the prospect of a takeover has increased. Other approvals of note include an early decision on Exelixis/Ipsen’s Cabometyx in combination with Bristol Myers Squibb’s Opdivo in first-line renal cell carcinoma, which could help cement Opdivo as leader in the space by 2026. Elsewhere, Darzalex Faspro, the subcutaneous version of J&J/Genmab’s anti-CD38 MAb, gained approval in patients with newly diagnosed light-chain (AL) amyloidosis. Jefferies analysts forecast $2bn worldwide peak sales for Darzalex outside multiple myeloma, predominantly in amyloidosis. The other big regulatory news last month was a three-month delay to the FDA’s decision on Biogen’s Alzheimer’s project aducanumab, a move that many interpreted positively and caused Biogen’s shares to rise 5.5%.

Notable first-time US approval decisions in January
Project	Company	2026e sales by indication ($m)	Outcome
Lupkynis (voclosporin)	Aurinia	1,092	Approved
Cabenuva (cabotegravir + rilpivirine)	GSK/J&J	681	Approved
Tepmetko (tepotinib)	Merck KGaA	492	No decision yet
Verquvo (vericiguat)	Merck/Bayer	389	Approved
Ansofaxine hydrochloride	Luye Pharma	-	No decision yet
Vocabria (oral cabotegravir)	Glaxosmithkline	-	Approved
Sources: EvaluatePharma & company releases.

 

Supplementary and other notable approval decisions in January
Product	Company	Indication (clinical trial)	Outcome
Xalkori	Pfizer	Paediatric patients with r/r systemic Alk-positive anaplastic large cell lymphoma (study ADVL0912 and A8081013)	Approved
Nplate	Amgen	Hematopoietic syndrome of acute radiation syndrome	Approved
Enhertu	Astrazeneca	Her2 +ve gastric or gastroesophageal junction (GEJ) adenocarcinoma (Destiny-Gastric01)	Approved
Xolair	Roche	Self-administration option across all approved US indications	No decision yet
Botox	Abbvie	Detrusor (bladder muscle) overactivity, paediatric patients	No decision yet
Estelle	Mithra	Prevent pregnancy	No decision yet
Darzalex Faspro	J&J/Genmab	AL amyloidosis (Andromeda, for use in combination with bortezomib, cyclophosphamide and dexamethasone)	Approved
Opdivo plus Cabometyx	Bristol/Exelixis	1L  renal cell carcinoma (Checkmate-9ER)	Approved (~1 month early)
Sources: EvaluatePharma & company releases. https://www.evaluate.com/vantage/articles/news/snippets/us-fda-approval-tracker-january

Pfizer sees $15bn of 2021 Covid sales; could it do $30bn?

 If Pfizer has got its sums right then the sellside might seriously have to lift forecasts for its Covid-19 vaccine Comirnaty. In today’s fourth-quarter earnings report the group said it expected to book $15bn of Comirnaty sales this year, but there is apparently room to approach a number twice as high. The $15bn forecast comprises only the 780 million or so doses Pfizer has already contracted for, including 200 million to the US for $3.9bn and 300 million to the EU. But the company can “potentially deliver around two billion doses by the end of 2021”, though because the market is subject to government contracting it says it is responsible not to bake such numbers into revenue forecasts. Pfizer is splitting Comirnaty gross margins 50/50 with Biontech, but will book sales globally except in Turkey and Germany, and expects a high-20s percentage pretax profit margin on the vaccine’s sales. In December the sellside saw Moderna’s mRNA-1273 as this year’s top-selling Covid-19 vaccine, and though some analysts now expect this to sell $11bn in 2021 Pfizer has jumped ahead; the first forecasts have also emerged for Astrazeneca’s AZD1222, from Leerink, which sees $1.9bn this year and $3bn in 2022.

https://www.evaluate.com/vantage/articles/news/snippets/pfizer-sees-15bn-2021-covid-sales-could-it-do-30bn

Sputnik V fails to come in from the cold

 Interim phase III data on Sputnik V, the adenovirus-based Covid-19 vaccine developed at the Gamaleya Research Institute in Russia, were reported in the Lancet today and look solid at first glance, with a respectable efficacy rate of 91.6%.

But two deaths associated with Covid-19 among the vaccine recipients might raise concerns, though the researchers insisted that these were due to pre-existing conditions, and that the patients had been infected before they were dosed. Other intriguing aspects are the use of different adenoviral vectors for the two doses, and the storage requirements for the vaccine, which might be more onerous than expected.  

Of the participants in the Resist trial, 16 of the 14,964 vaccine recipients and 62 of those given a placebo contracted the virus. The time point at which this was assessed was unusually strict: 21 days from the first dose, ie the date of the second dose. Pivotal studies of the other prime-boost vaccines that have reported data left at least a week after the second dose for immunity to develop before assessing efficacy.

Crucially, there were no cases of moderate or severe Covid-19 in the treatment group, versus 20 with placebo. Safety was clean, with no vaccine-related serious adverse events. 

But the deaths might rankle. They were caused by cardiovascular and endocrine conditions exacerbated by Covid-19, the authors said. More importantly, the two subjects died four and five days after their first doses, allowing the researchers to conclude that they had already been infected before being included in the study, despite negative PCR tests at enrolment.

There have been no Covid-19 deaths with the other vaccines on which phase III data have been reported.

Vaccine efficacy comparison
		Covid-19			Severe Covid-19		Covid-19 death
Company	Vaccine	Vaccine	Pbo	Efficacy	Vaccine	Pbo	Vaccine	Pbo
Pfizer/Biontech	BNT162b2	8	162	95%	1	9	0	0
Moderna	mRNA-1273	11	185	94%	0	30	0	1
Gamaleya Research Institute	Sputnik V	16	62	92%	0	20*	2**	0
Novavax	NVX-CoV2373	6	56	89%	0	1	0	0
Astrazeneca	AZD1222	30	101	70%	0	2	0	1
Johnson & Johnson	Ad26.COV2.S/ JNJ-78436735	66% effective		66%	85% effective		0	Unknown
*Moderate to severe cases. **Infections judged to predate vaccination. Source: company releases, the Lancet, the NEJM.

One intriguing aspect of Sputnik V is that it uses two different adenoviruses: the first dose is based on recombinant Ad26 and the second, 21 days later, on rAd5, with both vectors carrying the gene for the full-length spike protein.

The authors wrote that using a different vector for the booster might help create a more powerful immune response than using the same vector twice – as Astrazeneca’s vaccine does, for instance – as this minimised the risk of the immune system developing resistance to the initial vector.

A question for the future is what this means for redosing after a longer interval, such as for an annual booster. If recipients become less responsive to adenoviral vectors, will new vectors have to be found for each additional shot? Or will immunity to the vectors wane along with immunity to the coronavirus, allowing their reuse? 

Moscow rules

Other questions are also pressing. The Lancet paper did not include any data on the vaccine’s effectiveness against new variants of the coronavirus, so further trials will be needed to tease this out. 

And vaccine watchers will note that Sputnik V appears more effective than the other vaccines that can be stored conveniently in fridges – those from Astrazeneca, Novavax and Johnson & Johnson. But this is not in fact the case. The vaccine used in the Resist trial was in fact a liquid formulation that requires storage at -18°C, so in storage terms the vaccine used in the trial is more similar to the mRNA vaccine from Moderna, whose efficacy was 94%. 

The freeze-dried form of Sputnik V that can be stored in a fridge is approved by Russia’s Ministry of Health, but there do not seem to be any concrete phase III data backing it.

These issues will soon come under scrutiny by EU regulators; an MAA for the vaccine is expected to be filed this month. Sputnik V is already authorised for use in 16 countries, including Hungary, Belarus and Argentina, as well as in Russia itself, which approved the vaccine last August on the strength of phase II data. 

https://www.evaluate.com/vantage/articles/news/sputnik-v-fails-come-cold