Celgene’s Pomalyst gets breakthrough therapy amrk from FDA for HIV-Positive and Negative Kaposi Sarcoma

May 13, 2019 Off By BusinessWire

Celgene plans to submit sNDA by end of 2019

Celgene plans additional studies with the AIDS Malignancy Consortium
in U.S. and sub-Saharan Africa

SUMMIT, N.J.–(BUSINESS WIRE)–Celgene Corporation (NASDAQ:CELG) today announced that the U.S. Food and
Drug Administration (FDA) has granted Breakthrough Therapy designation
to POMALYST® (pomalidomide) for the treatment of patients with human
immunodeficiency virus (HIV)-positive Kaposi sarcoma who have previously
received systemic chemotherapy, as well as patients with HIV‐negative
Kaposi’s sarcoma.

Kaposi sarcoma is a multicentric tumor caused by Kaposi
sarcoma-associated herpesvirus, also called human herpesvirus-8.
Patients suffer multiple lesions on the skin and oral mucosa, and at
times other organs such as the lungs or gastrointestinal mucosa. Kaposi
sarcoma most commonly arises in persons infected with HIV. There is a
substantial need for new treatments because there are no approved
therapies for HIV-positive patients who are refractory to or intolerant
of systemic chemotherapy. Although the use of combination
anti-retroviral treatments (cART or HAART) has reduced the incidence of
advanced Kaposi sarcoma in the United States, there are still nearly
2000 new cases each year. The disease is more highly prevalent in areas
of the world where HIV treatments are less available, such as
sub-Saharan Africa, and in some countries is the most common tumor in
men overall.

“The encouraging news of the FDA Breakthrough Therapy designation for
POMALYST in Kaposi sarcoma reflects the urgency in accelerating the
development of therapies to address diseases of this type,” said Jay
Backstrom, M.D., Chief Medical Officer for Celgene. “We will continue to
work closely with the agency to move this program forward for patients
with this rare and serious cancer.”

The Breakthrough Therapy designation was granted by the FDA on the basis
of the results of a clinical study performed under a Cooperative
Research and Development Agreement (CRADA) by a team led by Dr. Robert
Yarchoan, of the HIV and AIDS Malignancy Branch within the Center for
Cancer Research of the National Cancer Institutes (NCI). The results of
that study, published in the Journal of Clinical Oncology (MN Polizzotto
et al, JCO, 2016, 34, 4125-31), evaluated POMALYST in patients with
Kaposi sarcoma, with or without HIV infection, many of whom had received
prior cytotoxic chemotherapy.

According to the FDA, Breakthrough Therapy designation is intended to
expedite the development and review of medicines with early evidence of
potential clinical benefit in serious diseases.

Celgene plans to submit a supplemental New Drug Application for POMALYST
in this disease area by the end of 2019.

Celgene also has two additional studies planned in this disease. In
partnership with the AIDS Malignancy Consortium (AMC), a U.S.
multicenter study will be performed to confirm and extend the results of
the NCI study. The AMC is also sponsoring a second study in sub-Saharan
Africa, where Kaposi sarcoma continues to be a serious problem. This
program is a part of the Celgene Global Health effort to discover and
develop new drugs for diseases that affect patients in the lower- and
middle-income countries where health systems and medical resources are
less advanced.

POMALYST is not approved for Kaposi sarcoma in any country.

About POMALYST

POMALYST is one of Celgene’s IMiD^® agents – proprietary small
molecule, orally-available compounds for the treatment of some blood
cancers. IMiD agents are hypothesized to have multiple mechanisms of
action and have become a foundation of multiple myeloma research, with a
growing number of studies exploring these compounds in different
settings and diseases.

U.S. Safety Information

Indication

POMALYST^® (pomalidomide) is a thalidomide analogue indicated,
in combination with dexamethasone, for patients with multiple myeloma
who have received at least two prior therapies including lenalidomide
and a proteasome inhibitor and have demonstrated disease progression on
or within 60 days of completion of the last therapy.

Important Safety Information

WARNING: EMBRYO-FETAL TOXICITY and VENOUS AND ARTERIAL
THROMBOEMBOLISM

Embryo-Fetal Toxicity

- POMALYST is contraindicated in pregnancy. POMALYST is a
  thalidomide analogue. Thalidomide is a known human teratogen
  that causes severe birth defects or embryo-fetal death. In
  females of reproductive potential, obtain 2 negative pregnancy
  tests before starting POMALYST treatment.
- Females of reproductive potential must use 2 forms of
  contraception or continuously abstain from heterosexual sex
  during and for 4 weeks after stopping POMALYST treatment.

POMALYST is only available through a restricted distribution
program called POMALYST REMS^®.

Venous and Arterial Thromboembolism

- Deep venous thrombosis (DVT), pulmonary embolism (PE),
  myocardial infarction, and stroke occur in patients with
  multiple myeloma treated with POMALYST. Prophylactic
  antithrombotic measures were employed in clinical trials.
  Thromboprophylaxis is recommended, and the choice of regimen
  should be based on assessment of the patient’s underlying risk
  factors.

CONTRAINDICATIONS

- Pregnancy: POMALYST can
  cause fetal harm and is contraindicated in females who are pregnant.
  If POMALYST is used during pregnancy or if the patient becomes
  pregnant while taking this drug, the patient should be apprised of the
  potential risk to a fetus.

WARNINGS AND PRECAUTIONS

- Embryo-Fetal Toxicity & Females of
  Reproductive Potential: See Boxed WARNINGS

- Males: Pomalidomide is present in the
  semen of patients receiving the drug. Males must always use a latex or
  synthetic condom during any sexual contact with females of
  reproductive potential while taking POMALYST and for up to 4 weeks
  after discontinuing POMALYST, even if they have undergone a successful
  vasectomy. Males must not donate sperm.

- Blood Donation: Patients must not donate
  blood during treatment with POMALYST and for 4 weeks following
  discontinuation of POMALYST therapy because the blood might be given
  to a pregnant female patient whose fetus must not be exposed to
  POMALYST.

- POMALYST REMS^®
  Program: See Boxed WARNINGS

- Prescribers and pharmacies must be certified with the POMALYST REMS
  program by enrolling and complying with the REMS requirements;
  pharmacies must only dispense to patients who are authorized to
  receive POMALYST. Patients must sign a Patient-Physician Agreement
  Form and comply with REMS requirements; female patients of
  reproductive potential who are not pregnant must comply with the
  pregnancy testing and contraception requirements and males must comply
  with contraception requirements.

- Further information about the POMALYST REMS program is
  available at www.CelgeneRiskManagement.com
  or by telephone at 1-888-423-5436.

- Venous and Arterial Thromboembolism: See
  Boxed WARNINGS. Patients with known risk factors, including
  prior thrombosis, may be at greater risk, and actions should be taken
  to try to minimize all modifiable factors (e.g., hyperlipidemia,
  hypertension, smoking). Thromboprophylaxis is recommended, and the
  choice of regimen should be based on assessment of the patient’s
  underlying risk factors.

- Increased Mortality with Pembrolizumab:
  In clinical trials in patients with multiple myeloma, the addition of
  pembrolizumab to a thalidomide analogue plus dexamethasone resulted in
  increased mortality. Treatment of patients with multiple myeloma with
  a PD-1 or PD-L1 blocking antibody in combination with a thalidomide
  analogue plus dexamethasone is not recommended outside of controlled
  clinical trials.

- Hematologic Toxicity:
  Neutropenia (46%) was the most frequently reported Grade 3/4 adverse
  reaction in patients taking POMALYST in clinical trials, followed by
  anemia and thrombocytopenia. Monitor complete blood counts weekly for
  the first 8 weeks and monthly thereafter. Patients may require dose
  interruption and/or modification.

- Hepatotoxicity: Hepatic
  failure, including fatal cases, has occurred in patients treated with
  POMALYST. Elevated levels of alanine aminotransferase and bilirubin
  have also been observed in patients treated with POMALYST. Monitor
  liver function tests monthly. Stop POMALYST upon elevation of liver
  enzymes. After return to baseline values, treatment at a lower dose
  may be considered.

- Severe Cutaneous Reactions Including
  Hypersensitivity Reactions: Angioedema and severe
  cutaneous reactions including Stevens-Johnson Syndrome (SJS), toxic
  epidermal necrolysis (TEN), and drug reaction with eosinophilia and
  systemic symptoms (DRESS) have been reported. DRESS may present with a
  cutaneous reaction (such as rash or exfoliative dermatitis),
  eosinophilia, fever, and/or lymphadenopathy with systemic
  complications such as hepatitis, nephritis, pneumonitis, myocarditis,
  and/or pericarditis. Discontinue POMALYST for angioedema, skin
  exfoliation, bullae, or any other severe cutaneous reactions such as
  SJS, TEN or DRESS, and do not resume therapy.

- Dizziness and Confusional State:
  In patients taking POMALYST in clinical trials, 14% experienced
  dizziness (1% Grade 3 or 4) and 7% a confusional state (3% Grade 3 or
  4). Instruct patients to avoid situations where dizziness or
  confusional state may be a problem and not to take other medications
  that may cause dizziness or confusional state without adequate medical
  advice.

- Neuropathy: In patients
  taking POMALYST in clinical trials, 18% experienced neuropathy (2%
  Grade 3 in one trial) and 12% peripheral neuropathy.

- Second Primary Malignancies: Cases
  of acute myelogenous leukemia have been reported in patients receiving
  POMALYST as an investigational therapy outside of multiple myeloma.

- Tumor Lysis Syndrome (TLS): TLS
  may occur in patients treated with POMALYST. Patients at risk are
  those with high tumor burden prior to treatment. These patients should
  be monitored closely and appropriate precautions taken.

ADVERSE REACTIONS

The most common adverse reactions for POMALYST (≥30%) included fatigue
and asthenia, neutropenia, anemia, constipation, nausea, diarrhea,
dyspnea, upper-respiratory tract infections, back pain, and pyrexia.

In the phase III trial, nearly all patients treated with POMALYST +
low-dose dex experienced at least one adverse reaction (99%). Adverse
reactions (≥15% in the POMALYST + low-dose dex arm and ≥2% higher than
control) included neutropenia (51.3%), fatigue and asthenia (46.7%),
upper respiratory tract infection (31%), thrombocytopenia (29.7%),
pyrexia (26.7%), dyspnea (25.3%), diarrhea (22%), constipation (21.7%),
back pain (19.7%), cough (20%), pneumonia (19.3%), bone pain (18%),
edema peripheral (17.3%), peripheral neuropathy (17.3%), muscle spasms
(15.3%), and nausea (15%). Grade 3 or 4 adverse reactions (≥15% in the
POMALYST + low-dose dex arm and ≥1% higher than control) included
neutropenia (48.3%), thrombocytopenia (22%), and pneumonia (15.7%).

DRUG INTERACTIONS

Avoid concomitant use of POMALYST with strong inhibitors of CYP1A2.
Consider alternative treatments. If a strong CYP1A2 inhibitor must be
used, reduce POMALYST dose by 50%.

USE IN SPECIFIC POPULATIONS

- Pregnancy: See Boxed WARNINGS. If
  pregnancy does occur during treatment, immediately discontinue the
  drug and refer patient to an obstetrician/gynecologist experienced in
  reproductive toxicity for further evaluation and counseling. There is
  a POMALYST pregnancy exposure registry that monitors pregnancy
  outcomes in females exposed to POMALYST during pregnancy as well as
  female partners of male patients who are exposed to POMALYST. This
  registry is also used to understand the root cause for the pregnancy.
  Report any suspected fetal exposure to POMALYST to the FDA via the
  MedWatch program at 1-800-FDA-1088 and also to Celgene Corporation at
  1-888-423-5436.

- Lactation: There is no
  information regarding the presence of pomalidomide in human milk, the
  effects of POMALYST on the breastfed child, or the effects of POMALYST
  on milk production. Pomalidomide was excreted in the milk of lactating
  rats. Because many drugs are excreted in human milk and because of the
  potential for adverse reactions in a breastfed child from POMALYST,
  advise women not to breastfeed during treatment with POMALYST.

- Pediatric Use: Safety and
  effectiveness have not been established in pediatric patients.

- Geriatric Use: No dosage
  adjustment is required for POMALYST based on age. Patients >65 years
  of age were more likely than patients ≤65 years of age to experience
  pneumonia.

- Renal Impairment: Reduce
  POMALYST dose by 25% in patients with severe renal impairment
  requiring dialysis. Take dose of POMALYST following hemodialysis on
  hemodialysis days.

- Hepatic Impairment: Reduce
  POMALYST dose by 25% in patients with mild to moderate hepatic
  impairment and 50% in patients with severe hepatic impairment.

- Smoking Tobacco: Advise
  patients that smoking may reduce the efficacy of POMALYST. Cigarette
  smoking reduces the AUC of pomalidomide by 32% by CYP1A2 induction.

Please see full Prescribing
Information, including Boxed WARNINGS.

About Celgene Global Health

Celgene Global Health (CGH) is a dedicated R&D unit of Celgene committed
to discovering, developing and delivering novel drugs for Diseases of
the Developing World (DDWs). Collaborating with non-profit and academic
institutions around the globe, CGH has utilized the company’s library of
more than 400,000 compounds to evaluate candidates for drug development
for DDWs. More than ten discovery and development programs are ongoing
in several disease areas such as malaria and tuberculosis. For more
information, visit https://www.celgene.com/responsibility/global-health/

About Celgene

Celgene Corporation, headquartered in Summit, New Jersey, is an
integrated global pharmaceutical company engaged primarily in the
discovery, development and commercialization of innovative therapies for
the treatment of cancer and inflammatory diseases through gene and
protein regulation. For more information, please visit the Company’s
website at www.celgene.com.
Follow Celgene on Social Media: @Celgene,
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FORWARD-LOOKING STATEMENTS

This press release contains forward-looking statements, which are
generally statements that are not historical facts. Forward-looking
statements can be identified by the words “expects,” “anticipates,”
“believes,” “intends,” “estimates,” “plans,” “will,” “outlook” and
similar expressions. Forward-looking statements are based on
management’s current plans, estimates, assumptions and projections, and
speak only as of the date they are made. Celgene undertakes no
obligation to update any forward-looking statement in light of new
information or future events, except as otherwise required by law.
Forward-looking statements involve inherent risks and uncertainties,
most of which are difficult to predict and are generally beyond our
control. Actual results or outcomes may differ materially from those
implied by the forward-looking statements as a result of the impact of a
number of factors, many of which are discussed in more detail in our
Annual Report on Form 10-K and other reports filed with the Securities
and Exchange Commission, including factors related to the proposed
transaction between Bristol-Myers Squibb and Celgene, such as, but not
limited to, the risks that: management’s time and attention is diverted
on transaction related issues; disruption from the transaction makes it
more difficult to maintain business, contractual and operational
relationships; legal proceedings are instituted against Bristol-Myers
Squibb, Celgene or the combined company could delay or prevent the
proposed transaction; and Bristol-Myers Squibb, Celgene or the combined
company is unable to retain key personnel