Biotech + pharma drug in combination with Immune checkpoint inhibitor improved progression-free survival of Advanced liver cancer patients

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https://www.bloomberg.com/press-rel...-inhibitor-significantly-improved-progression

Business

Exelixis and Ipsen Announce Cabozantinib in Combination with an Immune Checkpoint Inhibitor Significantly Improved Progression​

28 June 2021, 1:00 PM SGT
Exelixis and Ipsen Announce Cabozantinib in Combination with an Immune
Checkpoint Inhibitor Significantly Improved Progression-Free Survival in
Phase 3 COSMIC-312 Pivotal Trial in Patients with Previously Untreated
Advanced Liver Cancer

Business Wire

ALAMEDA, Calif. & PARIS -- June 28, 2021

 

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Regulatory News:

Exelixis, Inc. (NASDAQ: EXEL) and Ipsen (Euronext: IPN; ADR: IPSEY) today
announced that COSMIC-312, the ongoing phase 3 pivotal trial evaluating
cabozantinib (CABOMETYX®) in combination with atezolizumab versus sorafenib in
patients with previously untreated advanced hepatocellular carcinoma (HCC) met
one of the primary endpoints, demonstrating significant improvement in
progression-free survival (PFS) at the planned primary analysis. A
prespecified interim analysis for the second primary endpoint of overall
survival (OS), conducted at the same time as the primary analysis for PFS,
showed a trend favoring the combination of cabozantinib and atezolizumab, but
did not reach statistical significance. Based on the preliminary OS data,
Exelixis anticipates that the probability of reaching statistical significance
at the time of the final analysis is low. The trial will continue as planned
to the final analysis of OS; results are anticipated in early 2022.

 

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In the analysis of the primary endpoint of PFS in the PFS intent-to-treat
population, cabozantinib in combination with atezolizumab significantly
reduced the risk of disease progression or death by 37% compared with
sorafenib (hazard ratio

---

: 0.63; 99% confidence interval [CI]: 0.44-0.91;
P=0.0012). Safety for the combination appeared to be consistent with the known
safety profiles of the individual medicines, and no new safety signals were
identified. Exelixis plans to discuss the trial results and next steps for a
potential regulatory filing with the U.S. Food and Drug Administration (FDA).

“While we are encouraged by the data supporting the potential for the
combination of cabozantinib and atezolizumab to reduce the risk of disease
progression or death, we are disappointed by the interim result of lack of
significant improvement on overall survival versus the comparator arm,” said
Michael M. Morrissey, Ph.D., Exelixis’ President and Chief Executive Officer.
“As these data continue to mature, we are working to understand the potential
impact of various contributing factors on the results, including patient
demographics, subsequent anti-cancer therapy and the impact of COVID-19 on the
trial. We anticipate presenting the results at a future medical conference.”

 

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About COSMIC-312

COSMIC-312 is a global, multicenter, randomized, controlled phase 3 pivotal
trial that aimed to enroll approximately 840 patients at up to 200 sites
globally. Patients were randomized approximately 2:1:1 to one of three arms:
cabozantinib (40 mg) in combination with atezolizumab, sorafenib, or
cabozantinib (60 mg). Exelixis is sponsoring COSMIC-312, and Ipsen is
co-funding the trial. Genentech, a member of the Roche Group, is providing
atezolizumab for use in this trial. More information about COSMIC-312 is
available at ClinicalTrials.gov.

About HCC

More than 900,000 new cases of liver cancer, 90% of which are HCC, are
diagnosed worldwide each year.^1,2 HCC is a leading cause of cancer-related
death, expected to cause 1 million global deaths annually by 2030.^3 In the
U.S., HCC is the fastest-rising cause of cancer-related death.^4 Median
survival for patients with symptomatic advanced HCC who are treated with
systemic therapies is just 1 to 1.5 years.^2

 

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About CABOMETYX^® (cabozantinib)

In the U.S., CABOMETYX tablets are approved for the treatment of patients with
advanced renal cell carcinoma (RCC); for the treatment of patients with HCC
who have been previously treated with sorafenib; and for patients with
advanced RCC as a first-line treatment in combination with nivolumab. Outside
of the U.S., CABOMETYX is approved in 58 countries, including in the European
Union, the U.K., Norway, Iceland, Australia, New Zealand, Switzerland, South
Korea, Canada, Brazil, Taiwan, Hong Kong, Singapore, Macau, Jordan, Lebanon,
Russian Federation, Ukraine, Turkey, United Arab Emirates, Saudi Arabia,
Serbia, Israel, Mexico, Chile, Peru, Panama, Guatemala, Dominican Republic,
Ecuador, Thailand and Malaysia for the treatment of advanced RCC in adults who
have received prior VEGF-targeted therapy; in the European Union, the U.K.,
Norway, Iceland, Canada, Australia, Brazil, Taiwan, Hong Kong, Singapore,
Lebanon, Jordan, Russian Federation, Ukraine, Turkey, United Arab Emirates,
Saudi Arabia, Israel, Mexico, Chile, Peru, Panama, Guatemala, Dominican
Republic, Ecuador, Thailand and Malaysia for previously untreated
intermediate- or poor-risk advanced RCC; and in the European Union, the U.K.,
Norway, Iceland, Canada, Australia, New Zealand, Switzerland, Saudi Arabia,
Serbia, Israel, Taiwan, Hong Kong, South Korea, Singapore, Jordan, Russian
Federation, Ukraine, Turkey, Lebanon, United Arab Emirates, Peru, Panama,
Guatemala, Chile, Dominican Republic, Ecuador, Thailand and Malaysia for HCC
in adults who have previously been treated with sorafenib. In the European
Union, CABOMETYX is also approved in combination with nivolumab as first line
treatment for patients living with advanced RCC. In 2016, Exelixis granted
Ipsen exclusive rights for the commercialization and further clinical
development of cabozantinib outside of the United States and Japan. In 2017,
Exelixis granted exclusive rights to Takeda Pharmaceutical Company Limited for
the commercialization and further clinical development of cabozantinib for all
future indications in Japan. Exelixis holds the exclusive rights to develop
and commercialize cabozantinib in the United States.

CABOMETYX is not indicated as a treatment for previously untreated advanced
HCC.

 

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U.S. IMPORTANT SAFETY INFORMATION

WARNINGS AND PRECAUTIONS

Hemorrhage: Severe and fatal hemorrhages occurred with CABOMETYX. The
incidence of Grade 3 to 5 hemorrhagic events was 5% in CABOMETYX patients in
RCC and HCC studies. Discontinue CABOMETYX for Grade 3 or 4 hemorrhage. Do not
administer CABOMETYX to patients who have a recent history of hemorrhage,
including hemoptysis, hematemesis, or melena.

Perforations and Fistulas: Fistulas, including fatal cases, occurred in 1% of
CABOMETYX patients. Gastrointestinal (GI) perforations, including fatal cases,
occurred in 1% of CABOMETYX patients. Monitor patients for signs and symptoms
of fistulas and perforations, including abscess and sepsis. Discontinue
CABOMETYX in patients who experience a Grade 4 fistula or a GI perforation.

Thrombotic Events: CABOMETYX increased the risk of thrombotic events. Venous
thromboembolism occurred in 7% (including 4% pulmonary embolism) and arterial
thromboembolism in 2% of CABOMETYX patients. Fatal thrombotic events occurred
in CABOMETYX patients. Discontinue CABOMETYX in patients who develop an acute
myocardial infarction or serious arterial or venous thromboembolic events that
require medical intervention.

Hypertension and Hypertensive Crisis: CABOMETYX can cause hypertension,
including hypertensive crisis. Hypertension was reported in 36% (17% Grade 3
and <1% Grade 4) of CABOMETYX patients. Do not initiate CABOMETYX in patients
with uncontrolled hypertension. Monitor blood pressure regularly during
CABOMETYX treatment. Withhold CABOMETYX for hypertension that is not
adequately controlled with medical management; when controlled, resume at a
reduced dose. Discontinue CABOMETYX for severe hypertension that cannot be
controlled with anti-hypertensive therapy or for hypertensive crisis.

Diarrhea: Diarrhea occurred in 63% of CABOMETYX patients. Grade 3 diarrhea
occurred in 11% of CABOMETYX patients. Withhold CABOMETYX until improvement to
Grade 1 and resume at a reduced dose for intolerable Grade 2 diarrhea, Grade 3
diarrhea that cannot be managed with standard antidiarrheal treatments, or
Grade 4 diarrhea.

Palmar-Plantar Erythrodysesthesia (PPE): PPE occurred in 44% of CABOMETYX
patients. Grade 3 PPE occurred in 13% of CABOMETYX patients. Withhold
CABOMETYX until improvement to Grade 1 and resume at a reduced dose for
intolerable Grade 2 PPE or Grade 3 PPE.

Hepatotoxicity: CABOMETYX in combination with nivolumab can cause hepatic
toxicity with higher frequencies of Grades 3 and 4 ALT and AST elevations
compared to CABOMETYX alone.

Monitor liver enzymes before initiation of and periodically throughout
treatment. Consider more frequent monitoring of liver enzymes than when the
drugs are administered as single agents. For elevated liver enzymes, interrupt
CABOMETYX and nivolumab and consider administering corticosteroids.

With the combination of CABOMETYX and nivolumab, Grades 3 and 4 increased ALT
or AST were seen in 11% of patients. ALT or AST >3 times ULN (Grade ≥2) was
reported in 83 patients, of whom 23 (28%) received systemic corticosteroids;
ALT or AST resolved to Grades 0-1 in 74 (89%). Among the 44 patients with
Grade ≥2 increased ALT or AST who were rechallenged with either CABOMETYX
(n=9) or nivolumab (n=11) as a single agent or with both (n=24), recurrence of
Grade ≥2 increased ALT or AST was observed in 2 patients receiving CABOMETYX,
2 patients receiving nivolumab, and 7 patients receiving both CABOMETYX and
nivolumab.

 

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Adrenal Insufficiency: CABOMETYX in combination with nivolumab can cause
primary or secondary adrenal insufficiency. For Grade 2 or higher adrenal
insufficiency, initiate symptomatic treatment, including hormone replacement
as clinically indicated. Withhold CABOMETYX and/or nivolumab depending on
severity.

Adrenal insufficiency occurred in 4.7% (15/320) of patients with RCC who
received CABOMETYX with nivolumab, including Grade 3 (2.2%), and Grade 2
(1.9%) adverse reactions. Adrenal insufficiency led to permanent
discontinuation of CABOMETYX and nivolumab in 0.9% and withholding of
CABOMETYX and nivolumab in 2.8% of patients with RCC.

Approximately 80% (12/15) of patients with adrenal insufficiency received
hormone replacement therapy, including systemic corticosteroids. Adrenal
insufficiency resolved in 27% (n=4) of the 15 patients. Of the 9 patients in
whom CABOMETYX with nivolumab was withheld for adrenal insufficiency, 6
reinstated treatment after symptom improvement; of these, all (n=6) received
hormone replacement therapy and 2 had recurrence of adrenal insufficiency.

Proteinuria: Proteinuria was observed in 7% of CABOMETYX patients. Monitor
urine protein regularly during CABOMETYX treatment. Discontinue CABOMETYX in
patients who develop nephrotic syndrome.

Osteonecrosis of the Jaw (ONJ): ONJ occurred in <1% of CABOMETYX patients. ONJ
can manifest as jaw pain, osteomyelitis, osteitis, bone erosion, tooth or
periodontal infection, toothache, gingival ulceration or erosion, persistent
jaw pain, or slow healing of the mouth or jaw after dental surgery. Perform an
oral examination prior to CABOMETYX initiation and periodically during
treatment. Advise patients regarding good oral hygiene practices. Withhold
CABOMETYX for at least 3 weeks prior to scheduled dental surgery or invasive
dental procedures, if possible. Withhold CABOMETYX for development of ONJ
until complete resolution.

Impaired Wound Healing: Wound complications occurred with CABOMETYX. Withhold
CABOMETYX for at least 3 weeks prior to elective surgery. Do not administer
CABOMETYX for at least 2 weeks after major surgery and until adequate wound
healing is observed. The safety of resumption of CABOMETYX after resolution of
wound healing complications has not been established.

Reversible Posterior Leukoencephalopathy Syndrome (RPLS): RPLS, a syndrome of
subcortical vasogenic edema diagnosed by characteristic findings on MRI, can
occur with CABOMETYX. Evaluate for RPLS in patients presenting with seizures,
headache, visual disturbances, confusion, or altered mental function.
Discontinue CABOMETYX in patients who develop RPLS.

Embryo-Fetal Toxicity: CABOMETYX can cause fetal harm. Advise pregnant women
and females of reproductive potential of the potential risk to a fetus. Verify
the pregnancy status of females of reproductive potential prior to initiating
CABOMETYX and advise them to use effective contraception during treatment and
for 4 months after the last dose.

 

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ADVERSE REACTIONS

The most common (≥20%) adverse reactions are:

CABOMETYX as a single agent: diarrhea, fatigue, decreased appetite, PPE,
nausea, hypertension, vomiting, weight decreased, constipation, and dysphonia.

CABOMETYX in combination with nivolumab: diarrhea, fatigue, hepatotoxicity,
PPE, stomatitis, rash, hypertension, hypothyroidism, musculoskeletal pain,
decreased appetite, nausea, dysgeusia, abdominal pain, cough, and upper
respiratory tract infection.

DRUG INTERACTIONS

Strong CYP3A4 Inhibitors: If coadministration with strong CYP3A4 inhibitors
cannot be avoided, reduce the CABOMETYX dosage. Avoid grapefruit or grapefruit
juice.

Strong CYP3A4 Inducers: If coadministration with strong CYP3A4 inducers cannot
be avoided, increase the CABOMETYX dosage. Avoid St. John’s wort.

USE IN SPECIFIC POPULATIONS

Lactation: Advise women not to breastfeed during CABOMETYX treatment and for 4
months after the final dose.

Hepatic Impairment: In patients with moderate hepatic impairment, reduce the
CABOMETYX dosage. Avoid CABOMETYX in patients with severe hepatic impairment.

Please see accompanying full Prescribing Information
https://cabometyx.com/downloads/CABOMETYXUSPI.pdf.

You are encouraged to report negative side effects of prescription drugs to
the FDA. Visit www.FDA.gov/medwatch or call 1-800-FDA-1088.

EUROPEAN UNION IMPORTANT SAFETY INFORMATION

For detailed recommendations on the use of CABOMETYX in the European Union,
please see the Summary of Product Characteristics.

 

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AboutExelixis

Founded in 1994, Exelixis, Inc. (Nasdaq: EXEL) is a commercially successful,
oncology-focused biotechnology company that strives to accelerate the
discovery, development and commercialization of new medicines for
difficult-to-treat cancers. Following early work in model system genetics, we
established a broad drug discovery and development platform that has served as
the foundation for our continued efforts to bring new cancer therapies to
patients in need. Our discovery efforts have resulted in four commercially
available products, CABOMETYX^® (cabozantinib), COMETRIQ^® (cabozantinib),
COTELLIC^® (cobimetinib) and MINNEBRO^® (esaxerenone), and we have entered
into partnerships with leading pharmaceutical companies to bring these
important medicines to patients worldwide. Supported by revenues from our
marketed products and collaborations, we are committed to prudently
reinvesting in our business to maximize the potential of our pipeline. We are
supplementing our existing therapeutic assets with targeted business
development activities and internal drug discovery – all to deliver the next
generation of Exelixis medicines and help patients recover stronger and live
longer. Exelixis is a member of the Standard & Poor’s (S&P) MidCap 400 index,
which measures the performance of profitable mid-sized companies. In November
2020, the company was named to Fortune’s 100 Fastest-Growing Companies list
for the first time, ranking 17^th overall and the third-highest
biopharmaceutical company. For more information about Exelixis, please visit
www.exelixis.com, follow @ExelixisInc on Twitter or like Exelixis, Inc. on
Facebook.

 

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About Ipsen

Ipsen is a global mid-size biopharmaceutical company with a focus on
transformative medicines in Oncology, Rare Disease and Neuroscience. Ipsen
also has a well-established Consumer Healthcare business. With total sales
over €2.5 billion in 2020, Ipsen sells more than 20 drugs in over 110
countries, with a direct commercial presence in more than 30 countries.
Ipsen’s R&D is focused on its innovative and differentiated technological
platforms located in the heart of the leading biotechnological and life
sciences hubs (Paris-Saclay, France; Oxford, UK; Cambridge, US; Shanghai,
China). The Group has about 5,700 employees worldwide. Ipsen is listed in
Paris (Euronext: IPN) and in the United States through a Sponsored Level I
American Depositary Receipt program (ADR: IPSEY). For more information on
Ipsen, visit www.ipsen.com.

 

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https://www.macmillan.org.uk/cancer-information-and-support/treatments-and-drugs/cabozantinib

Cabozantinib is a type of targeted therapy drug called a tyrosine kinase inhibitor. It's used to treat medullary thyroid cancer and kidney cancer that has spread.

Cabozantinib (Cometriq®) capsules are used to treat medullary thyroid cancer that cannot be removed with an operation, or that has spread to other parts of the body.

Cabozantinib (Cabometyx®) tablets are used to treat a type of kidney cancer called renal cell cancer that has spread to other parts of the body. They may also be used to treat primary liver cancer.

Cabozantinib may sometimes be used to treat other cancers or as part of a clinical trial.

 

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What are targeted therapies?​

Targeted therapy uses drugs to find and attack cancer cells. There are many different types of targeted therapy. Each type targets something in or around the cancer cell that is helping it grow and survive.
You can read more about the most common types below. A targeted therapy can belong to more than one of these groups. For example, a monoclonal antibody may also block cancer cell growth. So it may also be called a cancer growth inhibitor. Some types of targeted therapy are also an immunotherapy.
If you know the name of the drug you are looking for, you can use our list of targeted and immunotherapy drugs to find it. This gives more information about:

• what each treatment is
• how it is given
• possible side effects.

 

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https://www.cancer.org/treatment/tr...munotherapy/immune-checkpoint-inhibitors.html​

​

Immune Checkpoint Inhibitors and Their Side Effects​

An important function of the immune system is its ability to tell between normal cells in the body and those it sees as “foreign.” This lets the immune system attack the foreign cells while leaving the normal cells alone. To do this, it uses “checkpoints.” Immune checkpoints are molecules on certain immune cells that need to be activated (or inactivated) to start an immune response.
Cancer cells sometimes find ways to use these checkpoints to avoid being attacked by the immune system. But drugs that target these checkpoints hold a lot of promise as cancer treatments. These drugs are called checkpoint inhibitors.
It's important to know that checkpoint inhibitors used to treat cancer don't work directly on the tumor at all. They only take the brakes off an immune response that has begun but hasn't yet been working at its full force.

 

[syed putra]

Its weird pharmaceuticals cannot raise billions to produce medicine like " tech start ups".

 

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https://ir.exelixis.com/news-releas...and-ipsen-enter-exclusive-licensing-agreement

Exelixis and Ipsen Enter into Exclusive Licensing Agreement to Commercialize and Develop Novel Cancer Therapy Cabozantinib in Regions Outside the United States, Canada and Japan

- Cabozantinib commercialized for medullary thyroid cancer (MTC) and filed for advanced renal cell carcinoma (RCC) -

- $200 million upfront payment and subsequent regulatory and commercial milestones -

SOUTH SAN FRANCISCO, Calif.& PARIS--(BUSINESS WIRE)--Feb. 29, 2016-- Exelixis, Inc.(NASDAQ:EXEL) and Ipsen(Euronext: IPN; ADR: IPSEY) today jointly announced an exclusive licensing agreement for the commercialization and further development of cabozantinib, Exelixis’ lead oncology drug. Under the agreement, Ipsen will have exclusive commercialization rights for current and potential future cabozantinib indications outside of the United States, Canada and Japan. This agreement includes rights to COMETRIQ®, which is currently approved in the European Union(EU) for the treatment of adult patients with progressive, unresectable, locally advanced or metastatic medullary thyroid cancer (MTC). The companies have agreed to collaborate on the development of cabozantinib for current and potential future indications. Exelixis will maintain exclusive commercial rights for cabozantinib in the United Statesand Canada, and continue its discussions to partner commercial rights in Japan.

Under the agreement, Exelixis will receive a $200 million upfront payment. Exelixis is eligible to receive regulatory milestones, including $60 million upon the approval of cabozantinib in Europefor advanced renal cell carcinoma (RCC) and $50 million upon the filing and approval of cabozantinib in Europe for advanced hepatocellular carcinoma (HCC), as well as additional regulatory milestones for potential further indications. The agreement also includes up to $545 million of potential commercial milestones and provides for Exelixis to receive tiered royalties up to 26% on Ipsen’s net sales of cabozantinib in its territories.

Marc de Garidel, Chairman and Chief Executive Officer of Ipsensaid: “The robust results from the METEOR study in advanced renal cell carcinoma demonstrate that cabozantinib has the potential to become a key oncology product in Europe. This transaction will help Ipsen accelerate the growth of the company and strengthen its oncology footprint in Europe. We are excited to bring cabozantinib to patients and clinicians around the world.”

Future commercial indications for cabozantinib could include advanced HCC, the subject of CELESTIAL, an Exelixis-sponsored phase 3 pivotal trial for which top-line results are anticipated in 2017. Additional earlier-stage studies are under way through Exelixis’ collaboration with the National Cancer Institute’s Cancer Therapy Evaluation Program (NCI-CTEP), and its ongoing Investigator-Sponsored Trial (IST) program. Through these two programs, there are more than 45 ongoing or planned studies including trials in advanced RCC, bladder cancer, colorectal cancer, non-small cell lung cancer, and endometrial cancer.

“In Ipsen, Exelixis has an ideal partner to maximize the potential for cabozantinib to have a positive impact on the treatment of cancer on a global basis,” said Michael M. Morrissey, Ph.D., President and Chief Executive Officer of Exelixis. “Ipsen’s established international oncology marketing presence, late-stage clinical development expertise and shared vision with Exelixis for the franchise potential of cabozantinib will accelerate cabozantinib’s commercialization in its territories, while Exelixisremains focused on our launch in the United States. While our immediate priority will be on advanced renal cell carcinoma, Exelixis and Ipsen are committed to exploring and potentially developing cabozantinib in a variety of cancer settings.”

 

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Its weird pharmaceuticals cannot raise billions to produce medicine like " tech start ups".

Is it? But the small ones are often bought up by big pharma isn’t it?

 

[syed putra]

Is it? But the small ones are often bought up by big pharma isn’t it?

Thats because they find it difficult to raise funds to produce and market the drugs themselves.

 

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Thats because they find it difficult to raise funds to produce and market the drugs themselves.

Today Exelixis share price dropped 23% after this news of phase 3 trial UPDATE. That must be why cannot raise billions to produce medicine. No wonder @eatshitndie don‘t buy fight cancer stock.

 

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Today Exelixis share price dropped 23% after this news of phase 3 trial UPDATE. That must be why cannot raise billions to produce medicine. No wonder @eatshitndie don‘t buy fight cancer stock.

Exelixis, Inc.
18.02
USD−5.40 (23.06%)today
Closed: 28 Jun, 4:14 pm GMT-4 · Disclaimer
After hours 18.08 +0.060 (0.33%)
NASDAQ: EXEL

 

[eatshitndie]

Today Exelixis share price dropped 23% after this news of phase 3 trial UPDATE. That must be why cannot raise billions to produce medicine. No wonder @eatshitndie don‘t buy fight cancer stock.

bought crispr (crsp) and intellia (ntla). both are gene editing startups.