AbbVie Submits Applications for Epcoritamab for Lymphoma Treatments

 

• European Medicines Agency (EMA) validates AbbVie's Marketing Authorization Application; Genmab submits Biologics License Application to U.S. Food and Drug Administration (FDA)
• The submissions are supported by the EPCORE™ NHL-1 open-label, multi-center Phase 2 trial evaluating the safety and preliminary efficacy of subcutaneous epcoritamab in adult patients with relapsed, progressive or refractory CD20+ mature B-cell non-Hodgkin's lymphoma (NHL)

AbbVie (NYSE: ABBV) today announced that the European Medicines Agency (EMA) has validated a Marketing Authorization Application (MAA) for epcoritamab (DuoBody^®-CD3xCD20), an investigational subcutaneous bispecific antibody, for the treatment of adult patients with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) after two or more lines of systemic therapy. Additionally, Genmab has submitted a Biologics License Application (BLA) to the U.S. Food and Drug Administration (FDA) for epcoritamab for the treatment of adult patients with R/R large B-cell lymphoma (LBCL) after two or more lines of systemic therapy.

https://www.biospace.com/article/releases/abbvie-announces-submissions-of-regulatory-applications-for-epcoritamab-duobody-cd3xcd20-for-the-treatment-of-relapsed-refractory-diffuse-large-b-cell-lymphoma-dlbcl-and-large-b-cell-lymphoma-lbcl-/

Outlook: FDA OKs Application for ONS-5010 as a Treatment for Wet AMD

 

• Prescription Drug User Fee Act (PDUFA) goal date of August 29, 2023

Outlook Therapeutics, Inc. (Nasdaq: OTLK), a biopharmaceutical company working to develop and launch the first FDA-approved ophthalmic formulation of bevacizumab for use in retinal indications, today announced that the U.S. Food and Drug Administration (FDA) has accepted for filing a Biologics License Application (BLA) for ONS-5010 / LYTENAVA™ (bevacizumab-vikg), an investigational ophthalmic formulation of bevacizumab for the treatment of wet age-related macular degeneration (wet AMD). The FDA set a Prescription Drug User Fee Act (PDUFA) goal date of August 29, 2023. ONS-5010, if approved, is expected to receive 12 years of regulatory exclusivity in the United States.

https://www.biospace.com/article/releases/outlook-therapeutics-announces-acceptance-of-biologics-license-application-by-u-s-fda-for-ons-5010-as-a-treatment-for-wet-amd/

FDA Adcomm to Meet on BioMarin's Hemophilia A Gene Therapy

 During its third-quarter earnings report, BioMarin Pharmaceutical noted that the FDA plans to hold an advisory committee meeting to discuss the company's gene therapy for hemophilia A. 

The Biologics License Application (BLA) for Roctavian (valoctocogene roxparvovec) was resubmitted on Oct. 12 and has a target action date of Mar. 31, 2023.

In the original announcement regarding the acceptance of the resubmission, the company said the FDA had not indicated there would be an advisory committee meeting.

Jeffrey Ajer, BioMarin's EVP and CMO, said in a conference call Thursday that the company is preparing for a potential launch based on the Mar. 31 PDUFA date.

"The cost of the therapy for the treatment of severe hemophilia A in the United States is high and well understood by payers," Ajer said.

Ajer noted that the Institute for Clinical and Economic Review (ICER), a drug-pricing watchdog in the U.S., had issued a report on Sept. 13 that suggested the possible U.S. price was appropriate.

"At a presumed price of $2.5 million, the report referred to Roctavian as a dominant treatment relative to emicizumab on cost-effectiveness. Roctavian was projected to have lower costs of $4 million, slightly higher quality-adjusted life years and slightly lower bleeds," Ajer said.

Henry Fuchs, BioMarin's president of worldwide research and development, appeared to welcome the advisory committee meeting, which has not been scheduled yet.

"This is something that we've been preparing for over the last few months," Fuchs said in the call. "We believe the [meeting] will provide a good forum to review the demonstrated bleeding control and established safety profile of Roctavian."

The AAV gene therapy Roctavian was approved in Europe on Aug. 24. In the U.S., the therapy received a Complete Response Letter on Aug. 18, 2020. 

The resubmission included two-year outcomes from all participants in the GENEr8-1 Phase III trial, which demonstrated stable and durable bleed control and a decrease in the mean annualized bleeding rate (ABR) and the mean annualized Factor VIII infusion rate.

The BLA resubmission also included data from five years of follow-up from the 6e13 vg/kg dose cohort in an ongoing Phase I/II dose escalation trial and a proposed long-term extension study that would follow participants for up to 15 years.

The company initially submitted a BLA in late 2019. The trials it was based on had positive results, but the FDA rejected the application, asking for at least two more years of follow-up data from each patient in the study.

Otherwise, BioMarin reported third-quarter revenues of $505.3 million, an increase of 24% compared to the same period the year before. The growth was driven by higher sales of Voxzogo, Naglazyme and Vimizim. Voxzogo is indicated for children with achondroplasia; Naglazyme is for mucopolysaccharidosis VI (MPS VI) and Maroteaux-Lamy syndrome; Vimizim is approved for Morquio A (MPS IVA).

https://www.biospace.com/article/fda-plans-to-hold-advisory-committee-meeting-on-biomarin-s-hemophilia-a-gene-therapy/

Industry's IL-2 Struggles Continue as Sanofi Drops Program

 Sanofi will drop its IL-2 candidate, citing a lack of efficacy in the early stages of data collection, the company announced in its Q3 report Friday.

The current 3-week dose schedule for the Phase II platform trials will be discontinued due to an early look at the data being "lower than projected," Sanofi reported. Safety-related issues were not a concern for the study, the company noted. 

Sanofi has been working on this IL-2 candidate since 2019 when it acquired San Diego-based Synthorx for a value of $2.5 billion. The deal gave Sanofi control over THOR-707, now known as SAR444245.

SAR444245 is Sanofi's precisely PEGylated, an engineered form of IL-2 with specificity and selectivity toward CD8+ T cells and Natural Killer cells. A novel amino acid inserted at a specific spot prevents the drug from binding to the CD25 alpha-submit while still allowing the drug to bind to the beta/gamma IL-2 receptors.

This highly differentiated non-alpha IL-2 candidate was being investigated for the treatment of numerous malignancies. In April of last year, interim data from the first-in-human trial to evaluate the safety, therapeutic activity and maximum tolerated dose showed the drug's particular promise as an immuno-oncology therapy. 

Now, Sanofi is reconsidering the dosing of the drug. A plan to initiate a new Phase I/II program with SAR444245 will be underway soon, the company announced. It will focus on solidifying the drug's foundation as a best-in-class target profile.

This decision was made based on "emerging external and internal data about non-alpha IL2's mechanism of action and therapeutic potential," according to the press release. 

Sanofi isn't the first company to lose sight of its IL-2 candidate. Nektar Therapeutics and Bristol Myers Squibb's IL-2 candidate, bempegaldesleukin, failed in its first phase III trial.

Other data-related decisions for Sanofi include discontinuing development programs for SAR443726 in atopic dermatitis and SAR443999 in an inflammatory indication due to the respective clinical profiles and portfolio considerations. 

Overall, Sanofi reported a 9% increase in sales growth driven by specialty care and vaccines. Flu, travel, PPH and meningitis vaccines drove drug sales. Regeneron collaboration Dupixent led specialty care increases and was also approved in the United States as the first and only treatment for adults with prurigo nodularis. 

https://www.biospace.com/article/sanofi-drops-program-releases-q3-report/

Eisai Responds to Claims Linking Patient Death to Lecanemab

 An investigator in the Phase III trial for Biogen and Eisai’s experimental Alzheimer's drug lecanemab is attributing a patient’s death to the drug. 

The unnamed study investigator said the death occurred in June following bleeding in the brain, and determined it was related to lecanemab treatment, according to STAT News, which broke the story Friday. 

Eisai, for its part, pointed to other possible factors such as multiple falls, a heart attack and mini stroke-like events.  

Libby Holman, senior director of product communications at Eisai U.S. did not confirm nor deny the investigator’s claim, in a written statement to BioSpace.

“Our studies are assessed by Eisai as well as independent data safety monitoring boards (DSMBs), comprised of external experts,” Holman said. “Eisai and the DSMBs review the safety data on an ongoing basis ... All the available safety information indicates that lecanemab therapy is not associated with an increased risk of death overall or from any specific cause." 

Holman confirmed the allegation of the patient’s death was related to ARIA, adding that “the independent DSMB completed a review of all ARIA-related safety data.”

BioSpace reached out to Biogen for comment and was forwarded to the Eisai communications team. 

Amyloid-related imaging abnormalities (ARIA) has been the primary serious adverse event connected with Biogen’s approved Alzheimer’s treatment, Aduhelm. In November, Biogen revealed it was investigating the death of a 75-year-old woman who died of ARIA while receiving Aduhelm.

ARIA, which includes cerebral edema, is associated with headache, confusion, nausea and gait disturbances. It is a known adverse event associated with anti-amyloid antibodies, a class that also includes lecanemab. Aduhelm’s label contains a warning to physicians to monitor for ARIA-E but not to necessarily remove patients from the drug.

Lecanemab sparked a new wave of optimism in the Alzheimer’s R&D space when Biogen and Eisai announced the drug had slowed disease progression in a Phase III trial. The new reports of the patient’s death have tempered this some, as Biogen’s shares took a hit in pre-market trading Friday.

In results the partners called “highly statistically significant” data from the CLARITY AD study showed lecanemab reduced the clinical decline of patients with mild to moderate Alzheimer’s by 27% compared to placebo after 18 months. This was based on the Clinical Dementia Rating-Sum of Boxes (CDR-SB) assessment. The experimental treatment slowed the loss of memory and thinking skills, according to the companies.

The rate of ARIA-H (ARIA cerebral microhemorrhages, cerebral macrohemorrhages, and superficial siderosis) was 17% in the lecanemab group compared to 8.7% in the placebo group. The ARIA-E rate was 12.5% in the lecanemab group and 1.7% in the placebo group.

“Eisai promptly communicates important safety information to sites, investigators and subjects through a variety of appropriate mechanisms including investigator communications, Independent Review Board communications and Informed Consent Form revisions,” Holman said in the statement.

https://www.biospace.com/article/eisai-responds-to-investigator-s-claims-linking-patient-death-to-lecanemab-/

Gilead's Hopes for HDV Approval Delayed after CRL

 Gilead's hopes for an approval in hepatitis delta virus (HDV) infection and compensated liver disease will have to wait following an FDA rejection.

The regulator issued a Complete Response Letter regarding Gilead's Biologics License Application for bulevirtide, an investigational entry-inhibitor treatment for HDV infection the company gained in its December 2020 acquisition of Germany's Myr GmbH.

The FDA cited concerns regarding the manufacture and delivery of bulevirtide, Gilead announced Thursday afternoon. 

At this time, Gilead noted the FDA has not requested any additional studies to evaluate the efficacy and safety of bulevirtide. The drug was previously granted conditional approval in Europe for the treatment of HDV, the most severe form of viral hepatitis, where it is marketed under the brand name Helcludex. 

There are currently no approved products for the treatment of HDV in the United States. 

During a quarterly financial call with investors Thursday, Gilead Chief Medical Officer Merdad Parsey said the company intends to take some time in order to "fully digest" the CRL.

With no safety or efficacy concerns raised by the FDA, Parsey said the company intends to work with the agency to resubmit the BLA as quickly as possible. He said the company remains confident of the benefits bulevirtide can bring to people in the U.S. battling HDV. 

"We'll share an update on the U.S. regulatory pathway when we can," Parsey said during the call. 

Parsey also noted in a separate statement that the FDA's rejection does not change the safety and efficacy profile that has been observed in clinical trials to date. He also stressed a critical unmet need for HDV treatment in the U.S. 

HDV occurs as a co-infection in individuals with the hepatitis B virus and can have mortality rates as high as 50% within five years in cirrhotic patients. 

Gilead has a solid presence in HBV with multiple marketed drugs, including Viread (tenofovir disoproxil fumarate, TDF) and Vemlidy (tenofovir alafenamide, TAF). Bulevirtide binds to NTCP, an essential HBV and HDV receptor on hepatocytes, and blocks the ability of the virus to attack. 

At the International Liver Congress in June, Gilead presented data supporting the efficacy of bulevirtide.

After 48 weeks of treatment, clinical data showed patients who were treated with two different dose levels of bulevirtide monotherapy, 2 mg and 10 mg, achieved a significantly greater combined virological and biochemical response of 45% and 48%, respectively, compared to patients who had not received antiviral treatment. 

Taken alongside other clinical data to date, Gilead stated the benefits of bulevirtide as monotherapy for treating chronic HDV are clinically evident.

Bulevirtide has been granted both Breakthrough Therapy and Orphan Drug designations by the FDA. 

Gilead's "Very Strong Quarter"

Despite the CRL, the company reported what Chief Executive Officer Dan O'Day called "a very strong quarter." It posted a three month revenue of $7 billion, a slight decrease from the same time the previous year. 

The slight drop in revenue was primarily due to decreased sales of the company's COVID-19 antiviral drug, Veklury. In all, sales of Veklury decreased by 52% to $925 million due to reduced COVID-19 infections. 

Primary growth areas for the company were driven by HIV, which generated about $4.5 billion in revenue, and oncology, O'Day said.

https://www.biospace.com/article/gilead-sciences-plans-for-winning-approval-for-hdv-drug-hit-snag-other-q3-news/

Fed expected to aggressively hike rates to 5%, triggering global recession: survey

 Federal Reserve officials are expected to maintain their hawkish stance at next week's policy-setting meeting where they are likely to approve another super-sized interest rate hike, paving the way for borrowing costs to climb above 5% by March 2023, according to a survey of Bloomberg economists. 

The survey found that most respondents expect the Fed to raise rates by 75 basis points for a fourth straight meeting. The Federal Open Market Committee will announce their decision following a two-day meeting on Tuesday and Wednesday. A basis point is one hundredth of one percent.

The U.S. central bank will then approve a 50 basis point increase in December, followed by 25 basis point increases at the following two meetings in February and March, participants predicted. The rapid tightening of policy is likely to trigger a U.S and global recession, according to the survey. 

"Inflation pressures remain intense and the Fed is set to hike by 75 basis points in November," James Knightley, chief international economist at ING Groep, said in a survey response. "We are currently forecasting a more muted 50 basis-point hike in December given a weakening economic and market backdrop."

Traders are pricing in a more than 80% chance of another 75 basis point hike at the conclusion of the Fed's two-day meeting next week, according to the CME Group's FedWatch tool, which tracks trading. Only 18% think the Fed will go with a half-point hike instead. The Fed has taken no action to dissuade that expectation. 

Officials may also take steps to push rates even higher than they had expected as recently as September as elevated inflation persists despite higher interest rates. The U.S. central bank had projected a peak rate of 4.6% next year, but that could increase depending on forthcoming economic data.

The U.S. central bank has embarked on one of the fastest courses in history to raise borrowing costs and slow the economy. Officials approved a third straight 75 basis point rate hike in September, lifting the federal funds rate to a range of 3.0% to 3.25% — near restrictive levels — and showed no signs of slowing down as they try to crush runaway inflation. 

A Labor Department report released earlier this month showed the consumer price index, a broad measure of the price for everyday goods including gasoline, groceries and rents, rose 0.4% in September from the previous month and 8.2% on an annual basis, far faster than experts anticipated.

"We haven’t yet made meaningful progress on inflation," Fed governor Christopher Waller said during a recent speech. 

In an even more concerning development that suggests underlying inflationary pressures in the economy remain strong, core prices, which strip out the more volatile measurements of food and energy, climbed 0.6% in September from the previous month. From the same time last year, core prices jumped 6.6%, the fastest since 1982. 

"CPI came in hot, which virtually guarantees the Fed will hike 75 basis points next month and at least 50 in December," said Robert Frick, corporate economist with Navy Federal Credit Union. "And we need to brace for more bad news in October and November as rising oil prices are likely to swing again from reducing to increasing inflation."

https://www.foxbusiness.com/economy/fed-expected-aggresively-hike-rate-triggering-global-recession-survey