Biotech Investors: Mark Your Calendar For June PDUFA Dates

 The FDA review machinery worked overtime in May, completing reviews of several drug applications. Except for stray rejections or delays, the agency churned out mostly positive outcomes.

New molecular entity approvals totaled five during the month. NMEs are drugs with active moieties or ingredients that have never been approved by the FDA previously, and are therefore indicators of drug innovation.

NME approvals for the month, included Apellis Pharmaceuticals, Inc.'s 

APLS 3.06% Empaveli, indicated for the treatment of paroxysmal nocturnal hemoglobinuria, Johnson & Johnson's JNJ 2.2% Rybrevant for a subtype of non-small cell lung cancer, Lantheus Holdings, Inc.'s LNTH 1.4% Pylarify, a fluorinated PSMA-targeted PET imaging agent for detecting prostate cancer, Amgen, Inc.'s KRAS G12C-targeted lung cancer treatment Lumakras and BridgeBio Pharma, Inc.'s BBIO 1.98% Truseltiq, indicated for biliary tract cancer.

Meanwhile, Eton Pharmaceuticals, Inc.'s ETON 12.04% new drug application for dehydrated alcohol injection was slapped with a complete response letter.

Here are the key FDA approvals scheduled for June.

SCYNEXIS Awaits Nod For Anti-fungal Treatment For Vaginal Yeast Infection

• Company: SCYNEXIS, Inc. SCYX 4.07%
• Type of Application: NDA
• Candidate: SCY-078 (oral ibrexafungerp)
• Indication: vulvovaginal candidiasis
• Date: June 1

The FDA accepted the application for priority review on Dec. 7. The investigational drug has both Qualified Infectious Disease Product, or QIDP, and Fast Track designations. The QIDP status vests the company with five years of market exclusivity, in addition to the five years of exclusivity as a chemical entity.

The company indicated it's continuing preparations for a commercial launch in the U.S. in the second half of 2021.

Vulvovaginal candidiasis, commonly known as a vaginal yeast infection due to Candida, is the second most common cause of vaginitis. The currently available treatment option is fluconazole approved way back in 1990. Fluxconzole faces shortcomings such as increasing resistance to it and upping the risk of miscarriage.

H.C. Wainwright estimates peak sales potential of $170 million for ibrexafungerp, assuming conservative net pricing of $170 million per prescription at launch and a conservative peak 5% market share.

Can Liminal's Plasminogen Replacement Therapy Cross The FDA Hurdle After Several Hiccups?

• Company: Liminal BioSciences Inc. LMNL 4.98%
• Type of Application: biologic license application
• Candidate: Ryplazim (plasminogen)
• Indication: Congenital plasminogen deficiency
• Date: June 5

Plasminogen, which will go by the trade name Ryplazim, is being evaluated for the treatment of congenital plasminogen deficiency. Plasminogen is a naturally occurring protein that is synthesized by the liver and circulates in the blood, and it is the main enzyme involved in the lysis of blood clots and clearance of extravasated fibrin.

Plasminogen, therefore, is vital for wound healing, cell migration, tissue remodeling, angiogenesis and embryogenesis.

The original BLA filed by Prometic Life Sciences in 2017 received a complete response the same year. A resubmission was done by Prometic, a subsidiary of Liminal, last September and following the acceptance of the filing, the FDA set a decision date of March 7. In early November, Liminal communication a three-month extension announced by the FDA, pushing the decision date to June 7.

‘No or no-go' For Biogen's Controversial Alzheimer's Drug

• Company: Biogen Inc. BIIB 0.12%
• Type of Application: BLA
• Candidate: Aducanumab
• Indication: Alzheimer's disease
• Date: June 7

Biogen resurrected aducanumab after shelving a couple of late-stage studies, thanks to subset analysis of data. It's an investigational human monoclonal antibody. The company had licensed the candidate from Neurimmune and is developing it along with Eisai Co., Ltd. ESALY 2.67%.

Biogen's BLA was accepted for review in August 2020, with a PDUFA date of March 8. An Adcom panel, which reviewed the BLA in November, voted against approving it. The negative verdict did not douse hopes of an eventual approval, given the dire need for a drug against this neurological disorder.

The company communicated in January a three-month extension in review period to June 7.

Alexion On Track For Third Label Expansion of Blood Disorder Drug

• Company: Alexion Pharmaceuticals, Inc. ALXN 0.39%
• Type of Application: supplemental NDA
• Candidate: Ultomiris
• Indication: paroxysmal nocturnal hemoglobinuria in children and adolescents
• Date: June 7

Alexion's Ultomiris was initially approved for PNH in adults in December 2018. Since then, it has received two label expansions. Alexion, which has agreed to be acquired by AstraZeneca Plc AZN 0.92%, is looking to expand the label to include the indication of PNH in children and adolescents.

PNH is a blood disorder characterized by complement-mediated destruction of the red blood cells that can cause a wide range of debilitating symptoms and complications, including thrombosis, which can occur throughout the body, and result in organ damage and premature death.

Can Vertex's Triple Combo Cystic Fibrosis Drug Get The Nod For Pediatric Usage

• Company: Vertex Pharmaceuticals Incorporated VRTX 0.5%
• Type of Application: sNDA
• Candidate: Trikafta
• Indication: cystic fibrosis in children
• Date: June 8

Trikafta, a triple combination of elexacaftor/tezacaftor/ivacaftor and ivacaftor, received its first approval in October 2019 as a treatment option for cystic fibrosis in people, ages 12 years and older, who have at least one F508del mutation in the cystic fibrosis transmembrane conductance regulator gene.

In December, the FDA expanded the eligibility for Trikafta to include people with cystic fibrosis, ages 12 years and older with certain mutations in the cystic fibrosis transmembrane conductance regulator.

Pfizer's Pneumonia Vaccine Targeting 20 Strains of Bacteria Awaits FDA Nod

• Company: Pfizer Inc. PFE 0.59%
• Type of Application: BLA
• Candidate: 20-valent pneumococcal conjugate (20vPnC) vaccine
• Indication: Pneumonia
• Date: June 8 (estimated)

The 20vPnC candidate vaccine is in development for the prevention of invasive disease and pneumonia caused by 20 serotypes of Streptococcus pneumoniae in the vaccine in adults ages 18 years and older.

Pfizer announced FDA's acceptance for priority review its BLA for the vaccine candidate on Dec. 8, 2020, with a PDUFA date of June.

Takeda Seeks Approval For Drug to Treat Inflammation of Esophagus

• Company: Takeda Pharmaceutical Company Limited TAK 2.4%
• Type of Application: NDA
• Candidate: TAK-721
• Indication: eosinophilic esophagitis
• Date: June 15 (estimated)

Eosinophilic esophagitis is a chronic, immune-mediated, inflammatory disease localized in the esophagus, and it currently doesn't have an FDA-approved treatment. TAK-721 is a mucoadherent topically active oral viscous formulation of budesonide.

The regulator accepted for priority review Takeda's application on Dec. 15, 2020.

Blueprint's Ayvakit Up Before FDA For Label Expansion

• Company: Blueprint Medicines Corporation BPMC 2.4%
• Type of Application: sNDA
• Candidate: Ayvakit
• Indication: advanced systemic mastocytosis
• Date: June 16

Ayvakit was initially approved by the FDA in January 2020 for the treatment of adults with unresectable or metastatic gastrointestinal stromal tumor harboring a PDGFRA exon 18 mutation.

The company is now looking to expand the label of the treatment to include advanced systemic mastocytosis, which is a group of rare diseases in which uncontrolled growth and accumulation of a type of white blood cells called mast cells occurs in one or more organs, including the gastrointestinal tract, spleen, lymph nodes and bone marrow.

Can Orphazyme Leave The ALS Debacle Behind?

• Company: Orphazyme A/S ORPH 0.54% and CytRx Corporation CYTR 416.13%
• Type of Application: NDA
• Candidate: Arimocolmol
• Indication: Niemann-Pick Disease Type C
• Date: June 17

NPC, according to the company, is a rare, relentlessly progressive, neurodegenerative disease, with an estimated incidence of one in 100,000 live births. The FDA had accepted the NDA for priority review on Sept. 16, 2020, and set a PDUFA goal date of March 17.

In Dec. 2020, the company said the FDA has delayed the decision by three months to June 17.

Orphazyme, a Denmark-based biopharma, is collaborating with Cytrx Corp. in developing arimocolmol, the only drug candidate in its pipeline. Incidentally, the drug failed in clinical trials for amyotrophic lateral sclerosis.

Will Eton's Ready-to-use Low Blood Pressure Medication Cross FDA Hurdle?

• Company: Eton Pharma
• Type of Application:
• Candidate: Ready-to-Use ephedrine injection
• Indication: low blood pressure
• Date: June 18

Eton sees market opportunity for the RTU ephedrine injection to be more than 10 million RTU units annually. This product candidate is an innovative ready-to-use formulation of a molecule that is currently approved in a concentrated formulation that must be diluted prior to administration to patients.

Eton's development partner, Sintetica, has submitted the product's NDA.

Incyte has Twin Binary Events In June

• Company: Incyte Corporation INCY 1.06%
• Type of Application: NDA/ sNDA
• Candidate: ruxolitinib cream/ ruxolitinib (Jakafi)
• Indication: atopic dermatitis/ steroid-refractory chronic graft-versus-host disease
• Date: June 21/22

Ruxolitinib cream, a selective JAK1/JAK2 inhibitor designed for topical application, as a treatment for atopic dermatitis, a type of eczema. Incyte's NDA was accepted for priority review on Feb. 19. Since the company has submitted a priority review voucher along with the NDA application for ruxolitinib cream, the review period gets shortened by four months.

The company is also seeking label expansion for Jakafi as a treatment option for steroid-refractory chronic graft-versus-host disease in adult and pediatric patients 12 years and older.

Ascendis Confident of Pediatric Growth Hormone Deficiency Prodrug Approval

• Company: Ascendis Pharma A/S ASND 0.63%
• Type of Application: BLA
• Candidate: TransCon hGH
• Indication: Pediatric growth hormone deficiency
• Date: June 25

TransCon hGH is being evaluated for the treatment of pediatric patients with growth hormone deficiency. It is an investigational prodrug of human growth hormome somatropin. The company is also developing a proprietary auto-injector to administer TransCon hGH, stable at room temperature, in dual-chamber cartridges.

Ascendis said in its first-quarter earnings report that pre-launch commercial activities are ongoing and the treatment candidate is scheduled to be launched in the U.S. in the third quarter of 2021.

"All FDA information requests relating to our BLA for TransCon hGH for the treatment of pediatric GHD have been responded to with no questions currently outstanding," it had said.

Decision Due On MediWound's Biologic Treatment For Thermal Wounds

• Company: MediWound Ltd. MDWD 3.24% & Vericel Corporation VCEL 0.02%
• Type of Application: BLA
• Candidate: NexoBrid
• Indication: severe thermal burns
• Date: June 29

The NexoBrid BLA, which requests approval for eschar removal in adults with deep partial-thickness and/or full-thickness thermal burns, was accepted for review in mid-September 2020. The FDA assigned a PDUFA goal date of June 29.

NexoBrid, a concentrate of proteolytic enzymes enriched in Bromelain, is a topically administered biological product that enzymatically removes non-viable burn tissue, or eschar, in patients with deep partial and full-thickness thermal burns within four hours of application without harming viable tissue.

NexoBrid is approved in the European Union and other international markets.

MediWound, an Israeli biopharma, has granted the North American license to NexoBrid to Vericel under a May 2019 agreement.

AbbVie's Rheumatoid Arthritis Drug Prepping For Label Expansion

• Company: AbbVie Inc. ABBV 0.9%
• Type of Application: sNDA
• Candidate: Rinvoq (updacitinib)
• Indication: active psoriatic arthritis.
• Date: late second quarter.

AbbVie announced that the FDA extended the review period for sNDA for Rinvoq in the treatment of adult patients with active psoriatic arthritis to late second quarter. The company clarified that the FDA made an information request for an updated assessment of the benefit-risk profile. Following the submission of information by AbbVie, the FDA required additional time for a full review of the submission.

Adcom Meetings

FDA's Vaccines and Related Biological Products Advisory Committee is scheduled to meet June 10 to discuss, in general, data needed to support authorization and/or licensure of COVID-19 vaccines for use in pediatric populations.

The Oncologic Drug Advisory Committee will meet June 24 to discuss Incyte's BLA for retifanlimab injection for the proposed indication of treating adult patients with locally advanced or metastatic squamous carcinoma of the anal canal, who have progressed on or who are intolerant of platinum-based chemotherapy.

https://www.benzinga.com/general/biotech/21/06/21365753/attention-biotech-investors-mark-your-calendar-for-june-pdufa-dates

Moderna partners with Thermo Fisher to scale up COVID-19 vaccine production

 Moderna Inc said on Tuesday it had entered into an agreement with Thermo Fisher Scientific for manufacturing and packaging its COVID-19 vaccine, as the U.S. vaccine maker looks to scale up production. 

  Under the terms, Moderna said Thermo Fisher's commercial manufacturing site in Greenville, North Carolina will be used to provide fill/finish manufacturing services and supply packaging for hundreds of millions of doses of the vaccine. 

  "The addition of Thermo Fisher to our network will support our efforts to scale up our manufacturing ability," Moderna's chief technical operations and quality officer, Juan Andres, said in a statement. 

  Earlier on Tuesday, Moderna filed for full U.S. approval of its COVID-19 vaccine for adults 

  Thermo Fisher said in March that it would work with Pfizer Inc and BioNtech SE to produce their COVID-19 vaccine in Italy. 

  In April, it announced a deal to buy contract researcher PPD Inc for $17.4 billion to add muscle to its pharmaceutical services business.

https://finance.yahoo.com/news/moderna-partners-thermo-fisher-scale-204346655.html

Novartis Cosentyx gets FDA OK for child, adolescent psoriasis

 Approval for moderate to severe pediatric patients six years and older is based on pivotal trial data showing Cosentyx demonstrated superior improvements of skin symptoms compared to placebo(1)

- The safety profile of Cosentyx in pediatric patients with plaque psoriasis was demonstrated in two Phase III trials(1)

- Plaque psoriasis is a chronic, inflammatory disease that may impact up to 350,000 children worldwide, with onset most common during adolescence(2,3)

https://www.prnewswire.com/news-releases/novartis-cosentyx-receives-fda-approval-for-treatment-of-children-and-adolescents-with-moderate-to-severe-plaque-psoriasis-301303365.html

Santhera scores in Duchenne

 Santhera has long claimed that, in vamorolone, it has a safer alternative to steroids for the treatment of Duchenne muscular dystrophy. This was borne out today by topline data from the pivotal Vision-DMD study, which compared vamorolone versus placebo and the steroid prednisone. The trial met its primary endpoint, time to stand, with vamorolone 6mg statistically superior to placebo at 24 weeks; a 2mg dose also hit on this measure. Also importantly, vamorolone was linked with fewer adverse events than prednisone, while the 6mg dose was similar on efficacy, Santhera said. Steroids are a mainstay of DMD therapy but can cause side effects including stunted growth and weight gain. Santhera plans to file vamorolone in the US in the first quarter of 2022. The Swiss group reckons vamorolone could bring in over $500m at peak in DMD, putting it among the top-selling therapies for the disorder, according to Evaluate Pharma. The company intends to market the drug alone in the US and EU; this could prove trickier than gaining approval, considering Santhera only has SFr26.4m ($29.4m) of available cash, including up to SFr18m that it can draw down from a Highbridge loan. The group’s stock shot up 50% this morning – still, it is only worth SFr46m

https://www.evaluate.com/vantage/articles/news/snippets/santhera-scores-duchenne.

Gene editing biotech Verve indicates swift swerve onto Wall Street, eyes $100M IPO

 Verve Therapeutics, on the march toward the clinic with a next-gen heart drug, wants a piece of the ever-growing biotech IPO pie.

Verve debuted just over two years ago with $58.5 million and a goal to bring one-and-done gene editing treatments to heart disease.  

Then, in January this year, the company began its march toward the clinic with a treatment for a genetic form of high cholesterol, raising an extra $94 million for its series B and work on the asset.

The treatment, VERVE-101, is a base editor, meaning it doesn’t cut DNA like CRISPR gene editing systems do. Instead, it changes one base, or letter, in the genome to a different one without affecting the letters around it. Its first target? An inherited form of high cholesterol called heterozygous familial hypercholesterolemia, or HeFH.

People with HeFH have a gene mutation in the liver that causes very high cholesterol levels and leads to heart attacks or strokes relatively early in life. VERVE-101 is designed to cut those cholesterol levels by blocking the PCSK9 gene.

With a target and a clinical plan, the young biotech is now seeking a quick turn onto the public markets, gunning for the standard $100 million IPO, though this could swell in the summer heat of biotech IPOs as many have before it.

Verve will use the cash toward its ongoing IND-enabling studies for VERVE-101, with plans to submit an IND next year, according to its SEC-1 filing.

The treatment is a lipid nanoparticle comprising a guide RNA to find the target letter on the PCSK9 and an mRNA that changes an A base in the gene to a G, thus inactivating the gene and lowering cholesterol.

Verve reported data last June showing the approach worked in monkeys. Two weeks after injection, the study found the treatment switched off the PCSK9 gene in 67% of liver cells, causing an 89% drop in PCSK9 protein in the monkeys’ blood and a 59% dip in LDL, or “bad,” cholesterol in their blood. Now, six months down the line, those changes have held.

Verve is starting with HeFH because it’s a serious disease with a clear genetic cause that’s hard to treat. After this first indication, though, Verve plans to branch out into bigger patient populations, first into “the more garden variety” atherosclerotic heart disease and then into the preventive setting.

Verve hopes a one-time gene editing injection could eliminate the hurdles facing cholesterol-lowering statins and other medicines. These include poor adherence, high costs, limited access and lack of insurance, Kathiresan said. And though approval and commercialization are still far out, Verve is already learning how it might roll out its treatments.

As Verve moves VERVE-101 toward the clinic, it will keep plugging along at its preclinical pipeline. Besides PCSK9, it has identified seven other genes, such as ANGPTL3, where loss-of-function mutations—mutations that “break” the gene—protect people from heart attacks. The company is evaluating whether base editing, CRISPR-based editing or an entirely different approach would work best for each target, the biotech told Fierce Biotech at the J.P Morgan annual healthcare conference earlier this year.

It plans to list on the Nasdaq under the ticker "VERV."

https://www.fiercebiotech.com/biotech/gene-editing-biotech-verve-indicates-a-swift-swerve-onto-wall-street-asking-for-100m-ipo

Is pharma ready to talk cure in cancer? Maybe with better access, screening, ASCO preview panel says

 As the American Society of Clinical Oncology conference preps to open this week, AstraZeneca asked cancer experts what they think about mentioning the C-word—in this case, cure—in talking about cancer treatment. 

The panel of cancer experts, oncologists, researchers and patient advocate leaders offered many perspectives and personal examples, but not surprisingly, didn’t come to a simple consensus.

Still, the hypothetical exercise shines a light on drug development advances—and the fact that some cancer cures are moving within reach. What will happen when drugs adopt, or at least consider using, the word “cure” in talking about cancer therapies?

“In one week’s time, we’ll have the opportunity to learn about some of the latest and most important advances in the oncology space and within that context, on the eve of the latest practice-changing (advances), it’s perfect that we’re having this conversation,” said David Fredrickson, AstraZeneca executive VP of its oncology business unit.

Christian Massacesi, senior VP and head of AstraZeneca's late-stage oncology development, related the story of his own uncle, who was diagnosed with late-stage cancer, facing a life expectancy of only a few months. But thanks to advanced therapies, his uncle is not only still alive six years later, but also cancer-free.

“Can we say he is cured? Probably we cannot. The science and the current data don’t tell us that for sure,” Massacesi said, adding that as a researcher at AstraZeneca, his mission now is developing treatments, like those for his uncle, that will “provide meaningful time to patients" but also ones "ultimately that can lead to cure.”

While the not-yet-cure words in use now by drugmakers, physicians and even patients may vary—remission, cancer-free, stable disease or even chronic condition—AstraZeneca’s panelists did agree on other issues. Especially the industry changes necessary to begin using the word cure legitimately.

Screening—earlier, more comprehensive and more of it—topped the list for many. Another important change is the need for ubiquitous and fair access across the full scope of cancer care.

“Do you really cure a disease if you have people who are left behind with it? ... The thing that keeps me up at night is does everyone benefit from the clinical trials we’re doing. Will everybody have access?” said Craig Emmitt Cole, M.D., who heads clinical research in hematology/oncology and multiple myeloma at the Michigan State University Breslin Cancer Center.

Elizabeth Franklin, president of the Cancer Support Community, agreed, adding, “There is actually no such thing as cure without equity. Period. … I don’t want to see a system of haves and have-nots, and I worry that when we see this rapid innovation, it’s going to benefit a certain group in our society. I want to make sure that when we talk about cure we are absolutely talking about cure for all.”

Patient perspectives, shown in a short video of opinions displayed onscreen, varied from those who said the word cure offers “false hope” and has “no place in clinical” discussions to another patient who said yes to the word because it “gives hope.”

Surgeon scientist Jonathan Spicer, M.D., medical director of the McGill Thoracic Oncology program, said that for many of his patients, cure is at the top of their agenda, although as he acknowledges “obviously it’s more complicated than that.”

He talked about a recent lung cancer surgical patient who was in her 30s. He successfully removed her tumor and offered the additional positive news that her tumor had a genetic indication for which there are targeted treatments.

“It was so important for me to tell her that she was cured, and it’s a very difficult conversation to have,” he said. “I don’t know whether she’ll have a recurrence or something down the road … There’s a lot on the line.”

As the panel moderator, Ron Winslow, a medical and science reporter formerly with The Wall Street Journal, chimed in—and perhaps the crux of the dilemma: “There is this sort of ‘you’re cured, but.’ There’s always that ‘but’ hanging in the air."

And that is the reality of the use of the word cure in cancer—at least for now.

https://www.fiercepharma.com/marketing/pharma-ready-to-talk-cure-cancer-astrazeneca-gathers-expert-panel-ahead-asco-to-debate

Nuwellis, Premier Enable Nationwide Access to Ultrafiltration Therapy

 Nuwellis, Inc. (Nasdaq: NUWE), formerly CHF Solutions, Inc., has been awarded a three-year national contract with Premier, Inc., effective today. The new Aquapheresis category agreement allows Premier members, at their discretion, to take advantage of special pricing and terms pre-negotiated by Premier for Aquadex SmartFlow®, the gentle fluid management technology developed by Nuwellis.

Aquadex® is the first and only therapy currently available in this newly-established Aquapheresis product category. The collaboration provides Nuwellis with the opportunity to expand into many of the thousands of hospitals with which Premier holds relationships.

“Premier is a trusted healthcare leader, and working with them to expand access to ultrafiltration with Aquadex is a significant milestone for the Company and the customers we serve,” said Nestor Jaramillo, Jr., President and CEO of Nuwellis. “The immense value of this collaboration will be felt by hospitals dedicated to offering its patients with the most innovative technology. We’re ultimately grateful for Premier’s dedication to deliver transformative solutions that power real results.”

Nuwellis is dedicated to transforming the lives of patients suffering from fluid overload – a condition associated with multiple disease states that can cause a significant burden on vital organs if left untreated. The Company prioritizes collaboration and innovation to provide unsurpassed care to pediatric, critical care and heart failure patients. Aquadex is built to gently remove excess fluid with customizable rates to improve patient outcomes.

Premier, Inc. is a leading healthcare improvement company, uniting an alliance of more than 4,100 U.S. hospitals and health systems and approximately 200,000 other providers and organizations to transform healthcare. With integrated data and analytics, collaboratives, supply chain solutions, and consulting and other services, Premier enables better care and outcomes at a lower cost.

https://finance.yahoo.com/news/nationwide-access-ultrafiltration-therapy-possible-120000488.html