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CytRx Announces Closing of Public Offering of Common Stock, Including Full Exercise of Underwriters’ Option to Purchase Additional Shares

On July 24, 2015 CytRx Corporation (Nasdaq: CYTR), a biopharmaceutical research and development company specializing in oncology, reported the closing of its previously announced underwritten public offering (Press release, CytRx, JUL 24, 2015, View Source;p=RssLanding&cat=news&id=2070943 [SID:1234506623]). The gross proceeds from its sale of 10,465,000 shares of common stock at a public offering price of $2.75 per share, including 1,365,000 shares sold pursuant to the full exercise of the underwriters’ option to purchase additional shares, were approximately $28.8 million prior to deducting underwriting discounts and commissions and offering expenses payable by CytRx.

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CytRx intends to use the net proceeds of the offering to fund clinical trials of its drug candidate aldoxorubicin and its drug discovery activities and for general corporate purposes, which may include pre-commercialization activities relating to aldoxorubicin, working capital, capital expenditures, research and development and other commercial expenditures.

Jefferies LLC acted as the sole book-running manager for the offering. Oppenheimer & Co. Inc., Aegis Capital Corp., FBR Capital Markets & Co., and H.C. Wainwright & Co. acted as co-lead managers for the offering.

The shares described above were sold pursuant to a shelf registration statement on Form S-3, including a base prospectus, previously filed with and declared effective by the Securities and Exchange Commission (SEC). The final prospectus supplement related to the offering also has been filed with the SEC. Copies of the final prospectus supplement and the accompanying prospectus may be obtained from Jefferies LLC, Equity Syndicate Prospectus Department, 520 Madison Avenue, 2nd Floor, New York, NY 10022, by email at [email protected] or by phone at 877-547-6340 or by accessing the SEC’s website at View Source

AbbVie Reports Second-Quarter 2015 Financial Results

On July 24, 2015 AbbVie (NYSE:ABBV) reported financial results for the second quarter ended June 30, 2015 (Press release, AbbVie, JUL 24, 2015, View Source;p=RssLanding&cat=news&id=2070868 [SID:1234506616]).

"We are pleased with the high level of performance we’ve delivered through the first-half of 2015, consistent with our commitment to shareholders for top-tier growth this year and beyond," said Richard A. Gonzalez, chairman and chief executive officer, AbbVie. "With the completion of the Pharmacyclics transaction, continued momentum from our on-market products and rapid evolution of our robust development pipeline, we are well positioned to deliver strong performance in the future."

Second-Quarter Results

Worldwide sales were $5.475 billion in the second quarter, up 11.1 percent year-over-year. On an operational basis, sales increased 19.4 percent, excluding an 8.3 percent unfavorable impact from foreign exchange rate fluctuations.

Second-quarter sales growth was driven by the continued strength of HUMIRA and other promoted products. Global HUMIRA sales increased 16.4 percent on an operational basis, or 7.6 percent including the impact of foreign exchange rate fluctuations. Strong U.S. HUMIRA growth continued, driven by double-digit growth across all three major market categories, rheumatology, dermatology and gastroenterology. Reported international HUMIRA sales growth in the quarter was reduced by nearly 18 percent due to unfavorable foreign exchange. First-half 2015 international HUMIRA sales grew nearly 9 percent on an operational basis, consistent with planning expectations and the full year forecast for international HUMIRA sales growth of 9 to 10 percent on an operational basis. As noted last quarter, the first-quarter international operational growth rate of nearly 15 percent was favorably impacted by the timing of shipments in select markets. Consequently, sales growth in the second quarter was negatively impacted by shipment timing.

Total company sales growth was also driven by $385 million in global VIEKIRA sales, now approved in 47 countries with additional approvals anticipated throughout the remainder of 2015, as well as strong operational growth from other key products including Creon, Synthroid and Duodopa.

Second-quarter U.S. IMBRUVICA sales were $234 million. AbbVie recorded a partial quarter of U.S. IMBRUVICA sales of $97 million and $10 million of international profit sharing based on the May 26 close date of the Pharmacyclics acquisition.

The adjusted gross margin ratio in the second quarter was 85.3 percent, excluding intangible asset amortization and other specified items. Gross margin expansion was driven by product mix, operating efficiencies and the impact of foreign exchange rates. The gross margin ratio under U.S. generally accepted accounting principles (GAAP) was 83.3 percent.

Adjusted selling, general and administrative (SG&A) expense was 25.1 percent of sales in the second quarter. On a GAAP basis, SG&A was 31.1 percent of sales.

Adjusted research and development (R&D) was 15.9 percent of sales in the quarter, reflecting funding actions in support of our mid- and late-stage pipeline assets. On a GAAP basis, R&D was 17.9 percent of sales.

The adjusted operating margin in the second quarter was 44.2 percent, compared to 36.4 percent in second-quarter 2014. On a GAAP basis, the operating margin was 33.8 percent.

Adjusted net interest expense was $137 million, which reflects the impact of debt issued in conjunction with the Pharmacyclics acquisition. The adjusted tax rate was 21.9 percent in the quarter and 18.6 percent on a GAAP basis.

Adjusted diluted earnings per share, excluding intangible asset amortization expense and other specified items, were $1.08 in the second quarter, up 31.7 percent. Diluted earnings per share were $0.83 on a GAAP basis.

Key Events from the Second Quarter

On May 26, AbbVie successfully completed the acquisition of Pharmacyclics, accelerating AbbVie’s clinical and commercial presence in oncology. The acquisition aligns strategically to AbbVie’s business model, strengthening the company’s already robust oncology pipeline and further diversifying AbbVie’s revenue base.

AbbVie announced that the European Commission granted marketing authorization for IMBRUVICA (ibrutinib) as the first treatment option specifically approved for treatment of adult patients with Waldenstrom’s macroglobulinemia.

Results from the Phase 3 HELIOS study of IMBRUVICA were presented at The American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) meeting. The data demonstrated that patients with relapsed/refractory chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) experienced an 80 percent reduction in the risk of disease progression or death when treated with ibrutinib in combination with bendamustine and rituximab, compared to patients receiving placebo in combination with bendamustine and rituximab.

AbbVie reported top-line results from the head-to-head Phase 3, RESONATE-2 study, which evaluated efficacy and safety of ibrutinib versus traditional chemotherapy, chlorambucil. Initial findings showed that treatment with ibrutinib improved progression-free survival rates, as well as met several secondary endpoints, including overall survival and overall response rates when used in treatment-naïve patients with CLL and SLL. Additional detailed data will be presented at an upcoming medical meeting. AbbVie anticipates submitting these data for regulatory review in the second-half of 2015.

AbbVie announced its investigational medicine venetoclax, an inhibitor of the B-cell lymphoma-2 (BCL-2) protein that is being developed in partnership with Genentech and Roche, has been granted Breakthrough Therapy Designation by the U.S. Food and Drug Administration (FDA) for the treatment of CLL in previously treated (relapsed/refractory) patients with the 17p deletion genetic mutation. The 17p deletion mutation is a genomic alteration in which a part of chromosome 17 is absent. The median life expectancy for CLL patients with 17p deletion is less than 2-3 years. AbbVie expects to submit regulatory applications to U.S. and European agencies for this indication before the end of 2015.

Data from the Phase 3 ELOQUENT-2 study of elotuzumab were recently published in the New England Journal of Medicine. Elotuzumab is being developed in partnership with Bristol Myers Squibb, for front-line and relapsed/refractory multiple myeloma. Data showed that adding elotuzumab to standard of care in patients with relapsed/refractory multiple myeloma significantly reduced the risk of disease progression and demonstrated superior progression-free survival and overall response rates. The regulatory submissions are anticipated in the second-half of 2015.

The FDA granted priority review to AbbVie for its investigational, all-oral, interferon-free (IFN) therapy for the treatment of genotype 4 (GT4) chronic HCV in the United States. The New Drug Application (NDA) was accepted by the agency and is based on results from the PEARL-I study, which demonstrated 100 percent sustained virologic response rate at 12 weeks post-treatment (SVR12) when used with ribavirin (RBV), with no discontinuations due to adverse events. This investigational therapy also previously received Breakthrough Therapy Designation, and AbbVie anticipates regulatory action in the second-half of 2015.
New, pivotal data from the GIFT-I study of AbbVie’s all-oral, IFN- and RBV-free, two direct-acting antiviral (DAA) treatment with ombitasvir/paritaprevir/ritonavir in genotype 1b (GT1b) chronic HCV infected Japanese patients with and without cirrhosis were presented at the Annual Meeting of the Japan Society of Hepatology. Patients were both treatment-naïve and treatment-experienced. Primary endpoints were achieved, demonstrating 95 percent SVR12 in a sub-group of treatment-naïve, non-cirrhotic, adult GT1b chronic HCV infected Japanese patients who were eligible for therapy with IFN and had a high viral load. In study results related to the secondary endpoint, GT1b HCV patients with compensated cirrhosis achieved 91 percent SVR12. AbbVie’s two-DAA combination is currently under regulatory review in Japan and a decision is expected in the second-half of 2015.
AbbVie reported results from the TURQUOISE-III study in treatment-naïve and treatment-experienced patients with GT1b chronic HCV with compensated liver cirrhosis. These data demonstrated 100 percent SVR12 rates when treated with VIEKIRA without RBV. No patients discontinued treatment due to adverse events. Over time, chronic HCV may lead to liver complications, including compensated cirrhosis, in about 10-20 percent of people infected.

AbbVie announced that the FDA granted VIEKIRA orphan drug designation for the investigational treatment of HCV infection in pediatric patients, 0 – 16 years of age. Orphan drug designations recognize the need for a treatment of a rare disease or condition. AbbVie will conduct an investigational clinical study to evaluate the efficacy and safety of VIEKIRA with or without RBV in pediatric patients with chronic HCV infection. VIEKIRA is currently not approved for this indication.

AbbVie announced that the FDA granted HUMIRA orphan drug designation for the investigational treatment of moderate-to-severe hidradenitis suppurativa (HS), a painful, chronic inflammatory skin disease. AbbVie’s supplemental Biologic License Application (sBLA) is currently under review with the agency. The European Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) recently granted a positive opinion for this indication.

AbbVie recently received approval from the EMA for a new HUMIRA formulation, specifically designed to reduce injection pain and reduce injection volume.

AbbVie announced results from VISUAL‑I, a Phase 3 study investigating the efficacy and safety of HUMIRA in adult patients with uveitis. Results showed HUMIRA significantly lowered their risk of uncontrolled uveitis or vision loss. In May 2014, AbbVie received orphan drug designation from the FDA for the investigational treatment of certain forms of non‑infectious uveitis with HUMIRA. U.S. and EU regulatory submissions are expected in the second-half of 2015, following positive results from the second pivotal trial.
On June 18, the AbbVie board of directors declared a quarterly cash dividend of $0.51 per share, payable Aug. 14, 2015 to stockholders of record at the close of business on July 15, 2015. Since the company’s inception in 2013, AbbVie has increased its dividend by 28 percent.

Full-Year 2015 Outlook

AbbVie is confirming its adjusted diluted earnings-per-share guidance for the full-year 2015 of $4.10 to $4.30. The company’s 2015 adjusted diluted earnings-per-share guidance excludes $0.84 per share of intangible asset amortization expense, deal costs, integration, and other specified items, and includes $0.20 of dilution related to the Pharmacyclics acquisition. AbbVie’s diluted earnings-per-share guidance is $3.26 to $3.46 on a GAAP basis.

Molecular Partners confirms its focus on proprietary oncology pipeline – discovery alliance with Roche discontinued

On July 24, 2015 Molecular Partners AG (ticker: MOLN) reiterated its commitment to its un-partnered pipeline. This includes advancing the clinical and preclinical development pipeline and ramping up the activities in immuno-oncology (Press release, Molecular Partners, JUL 24, 2015, View Source [SID:1234506696]).

Following Molecular Partners’ expansion of its strategic ophthalmology partnership with Allergan, the company confirmed the discontinuation of the DARPin-toxin alliance with Roche.

Molecular Partners had entered into an oncology alliance with Roche in December 2013. Under this partnership, Roche and Molecular Partners generated DARPin-toxin fusion candidates. Roche is currently terminating its Pseudomonas exotoxin conjugate programs, including antibody and DARPin-based projects. The agreement put in place between Molecular Partners and Roche was specific for the use of DARPins in combination with Pseudomonas exotoxin.

"The DARPin platform generated highly differentiated binders in short time, and it is unfortunate that Roche decided to discontinue these programs for reasons related to the toxin," said Christian Zahnd, Chief Executive Officer of Molecular Partners and continued: "We discussed other areas of mutual interest, but given our own proprietary focus on immuno-oncology, it made no sense to amend the current collaboration. This way, we can avoid working on potentially competing pathways."

Molecular Partners will evaluate if DARPins from the collaboration will be added to its proprietary pipeline directly or repurposed in other programs.

Molecular Partners is advancing a growing proprietary pipeline of DARPin therapies in oncology. The most advanced systemic DARPin is MP0250 is in Phase 1 clinical studies in solid tumors. MP0250 inhibits both VEGF and HGF from binding to their receptors, thereby blocking tumor growth and tumor spreading. The second most advanced oncology DARPin is MP0274 and has broad anti-HER activity inhibiting both downstream HER2 and HER3-mediated signaling and leading to induction of apoptosis. MP0274 is currently in preclinical development. The current focus of Molecular Partners in research is immuno-oncology.

ZIOPHARM Announces Orphan Drug Designation for Ad-RTS-hIL-12 in the Treatment of Malignant Glioma

On July 24, 2015 ZIOPHARM Oncology, Inc. (Nasdaq:ZIOP), a biopharmaceutical company focused on the development and commercialization of new cancer therapies, reported that the U.S. Food and Drug Administration (FDA) has granted Orphan Drug Designation for Ad-RTS-hIL-12 + veledimex in the treatment of patients with malignant glioma (Press release, Ziopharm, JUL 24, 2015, View Source [SID:1234506625]). Ad-RTS-hIL-12 is a novel gene therapy candidate for the controlled expression of IL-12, a critical protein for stimulating an anti-cancer T cell immune response.

The FDA’s Office of Orphan Products grants orphan drug status to support development of medicines for underserved patient populations or rare disorders affecting fewer than 200,000 people in the U.S. Orphan Drug Designation provides eligibility for a seven-year period of market exclusivity in the United States after product approval, an accelerated review process, accelerated approval where appropriate, grant funding, tax benefits and an exemption from user fees.

"Malignant glioma is an aggressive cancer with few treatment options," said Laurence J. N. Cooper, M.D., Ph.D., Chief Executive Officer of ZIOPHARM. "This designation supports our effort to advance Ad-RTS-IL-12, a novel immuno-oncology therapy which has demonstrated promising preclinical efficacy in brain cancer, as a potential treatment for this indication. Enrollment in our Phase 1 study is progressing well, and we look forward to early results from this clinical trial later in the year."

Ad-RTS-hIL-12 + veledimex is currently being studied in a Phase 1 trial designed to examine a gene therapy treatment strategy for high grade gliomas, with the goal of generating an anti-tumor T cell immune response. The primary objective of the study is to determine the safety and tolerability of a single intra-tumoral Ad-RTS-hIL-12 injection plus escalating oral veledimex doses. Secondary objectives are to determine the veledimex maximum tolerated dose, the immune responses elicited by Ad-RTS-hIL-12 and veledimex, and investigator assessment of response, including the tumor objective response rate and progression-free survival, and determine overall survival, among other measures. The study is expected to enroll up to 72 subjects at up to 12 leading treatment centers.

FDA approves Novartis drug Odomzo® (sonidegib) for locally advanced basal cell carcinoma (laBCC), a form of skin cancer

On July 24, 2015 Novartis reported the US Food and Drug Administration (FDA) has approved Odomzo (sonidegib, formerly LDE225) 200 mg capsules for the treatment of adult patients with locally advanced basal cell carcinoma (laBCC) that has recurred following surgery or radiation therapy, or those who are not candidates for surgery or radiation therapy (Press release, Novartis, JUL 24, 2015, View Source [SID:1234506624]).

"The FDA approval of Odomzo offers a new and non-invasive treatment option for a potentially devastating disease that is hard to treat and can be disfiguring," said Bruno Strigini, President, Novartis Oncology. "Odomzo is an important addition to our growing portfolio of targeted treatments for advanced skin cancers and underscores our commitment to developing and bringing to market new options for patients."

The Odomzo approval was based on the demonstration of a durable objective response rate (ORR) in an international, multi-center, double-blind, randomized, two-arm, non-comparative trial in patients with laBCC not amenable to local therapy or metastatic basal cell carcinoma (mBCC) [1].

Patients with laBCC treated with Odomzo 200 mg (n=66) were followed for at least 12 months unless discontinued earlier. The ORR was 58% (95% confidence interval: 45, 70), consisting of 5% (n=3) complete responses (CR) and 53% (n=35) partial responses (PR). A pre-specified sensitivity analysis using an alternative definition for CR, defined as at least a PR according to MRI and/or photography and no evidence of tumor on biopsy of residual lesion, yielded a CR rate of 20%[1]. Among the 38 patients with an objective response, 31 patients (82%) have ongoing responses ranging from at least 1.9 to 18.6 months and the median duration of response has not been reached [1].

The most serious risks of Odomzo are embryofetal toxicity and musculoskeletal adverse reactions including rhabdomyolysis. Musculoskeletal adverse reactions, which may be accompanied by serum creatine kinase (CK) elevations, may occur with Odomzo and other drugs which inhibit the hedgehog pathway. The incidence of musculoskeletal adverse reactions in patients with laBCC treated with Odomzo 200 mg was 68%, with 9% reported as grade 3 or 4. Adverse reactions occurring in more than 10% of patients treated with Odomzo 200 mg were muscle spasms, alopecia, dysgeusia, fatigue, nausea, musculoskeletal pain, diarrhea, decreased weight, decreased appetite, myalgia, abdominal pain, headache, pain, vomiting, and pruritus. The most frequent grade 3 and 4 laboratory abnormalities occurring in at least 5% of patients were serum creatine kinase (CK) elevation and lipase elevation[1].

About the BOLT Clinical Trial
Data from the Phase II, randomized, double-blind multicenter BOLT (Basal cell carcinoma Outcomes in LDE225 Trial) formed the basis of the FDA’s approval. The primary endpoint was ORR of patients treated with Odomzo 200 mg and 800 mg, defined as the proportion of patients with confirmed complete or partial tumor response, or shrinkage, as measured by a central review committee. There was no evidence of better ORR among patients with laBCC randomized to receive Odomzo 800 mg daily[1].

The evaluation of tumor response was based on a composite assessment of modified Response Evaluation Criteria in Solid Tumors (mRECIST) that integrated tumor measurements obtained by radiographic assessments of target lesions (per RECIST 1.1), digital clinical photography (World Health Organization (WHO) adapted criteria), and histopathology assessments (via punch biopsies). All modalities used must have demonstrated absence of tumor to achieve a composite assessment of CR[1].

About Basal Cell Carcinoma
BCC consists of abnormal, uncontrolled growths or lesions that arise in the skin’s basal cells, which line the deepest layer of the epidermis (the outermost layer of the skin)[6] and accounts for more than 80% of non-melanoma skin cancers[7]. It occurs most frequently on the head and neck, with the nose being the most common site[7]. BCC that spreads from where it started to nearby tissue is called locally advanced[8] and can be highly disfiguring[2]. Advanced BCC is thought to represent roughly 1-10% of all cases of BCC[9]-[11]. While BCC is generally diagnosed and treated early, it may recur in an estimated 3% of patients after five years[12]. Although BCC rarely becomes advanced, there have been few treatment options at this stage of the disease. Worldwide incidence of BCC is rising by 10% each year due to factors such as an aging population and increased ultraviolet exposure. Incidence rates are estimated to be between 0.003% and 0.55% worldwide[13].

About Odomzo
Odomzo (sonidegib, formerly LDE225) is an oral, selective smoothened (SMO) inhibitor approved by the FDA for the treatment of adult patients with locally advanced basal cell carcinoma (laBCC) that has recurred following surgery or radiation therapy, or those who are not candidates for surgery or radiation therapy[1]. SMO is a molecule that regulates the hedgehog (Hh) signaling pathway, which plays a critical role in stem cell maintenance and tissue repair, as well as in advanced basal cell carcinoma[3]-[5]. Odomzo is currently in clinical development in other diseases.

Odomzo was approved in Switzerland for the treatment of advanced BCC that is not amenable to curative surgery or radiotherapy on June 30, 2015. The CHMP granted a positive opinion on June 25, 2015. Additional regulatory submissions are being reviewed by health authorities worldwide.

IMPORTANT SAFETY INFORMATION
Important note: Before prescribing, consult the full prescribing information.

Presentation: Hard gelatin capsules containing 200 mg sonidegib.

Indications: Odomzo is indicated for the treatment of adult patients with locally advanced basal cell carcinoma (BCC) who are not amenable to curative surgery or radiation therapy.

Dosage and administration: Adults: One 200 mg dose taken orally once daily on an empty stomach, at the same time each day. Children: Safety and effectiveness has not been established in pediatric patients with BCC.

Patients with renal impairment: Sonidegib has not been studied in patients with renal impairment. Based on available data, sonidegib elimination via the kidney is negligible. A population pharmacokinetic analysis did not find significant influence of renal function on the apparent clearance (CL/F) of sonidegib suggesting that dose adjustment is not necessary in patients with renal impairment.

Patients with hepatic impairment: No dose adjustment necessary in patients with mild (Child-Pugh class A) or moderate (Child-Pugh class B) hepatic impairment. Sonidegib has not been studied in patients with severe hepatic impairment (Child-Pugh class C). Caution should therefore be used in patients with severe hepatic impairment.

Contraindications: Women who are pregnant or breast-feeding.

Warnings and precautions:
Muscle related adverse events: Creatine phosphokinase (CK) levels should be checked prior to starting treatment and as clinically indicated thereafter, for example, if muscle related symptoms are reported. If clinically notable elevation of CK is detected, renal function should be assessed. Dose modification or interruption guidelines should be followed. Patients should be closely monitored for muscle related symptoms if Odomzo is used in combination with certain medications that may increase the potential risk of developing muscle toxicity (e.g. CYP3A4 inhibitors, chloroquine, hydroxychloroquine, fibric acid derivatives, penicillamine, zidovudine, niacin, HMG-CoA reductase inhibitors).

Closely monitor patients with neuromuscular disorders (e.g. inflammatory myopathies, muscular dystrophy, amyotrophic lateral sclerosis and spinal muscular atrophy) due to an increased risk of muscle toxicity.

Blood donation: Patients should be instructed not to donate blood while taking Odomzo and for at least 20 months after ending treatment.

Women of child-bearing potential:
Women of childbearing potential must use a highly effective method of contraception while receiving Odomzo. Contraception must be continued for 20 months after ending treatment.

Pregnancy: Negative pregnancy status must be confirmed by a test performed by a health care provider prior to initiation of Odomzo treatment. Odomzo must not be used during pregnancy.

Breast-feeding: Women must not breast feed while taking Odomzo and for at least 20 months after ending treatment.

Sexually active males: Men should not father a child or donate semen while taking Odomzo and for at least 6 months after ending treatment. Sexually active males must use a condom, regardless of vasectomy status, during intercourse and for at least 6 months after ending treatment to prevent exposure of female partners to the drug via seminal fluid.

Fertility: Male and female fertility may be compromised with Odomzo. Fertility preservation strategies should be discussed prior to starting treatment with Odomzo.

Adverse drug reactions:
Very common (>=10%): amenorrhea, decreased appetite, dysgeusia, headache, nausea, diarrhea, vomiting, abdominal pain, alopecia, pruritus, muscle spasms, myalgia, musculoskeletal pain, fatigue, pain, weight decreased.
Common (between 1 to 10%): constipation, dyspepsia, gastroesophageal reflux disorder, rash, abnormal hair growth, myopathy (muscular fatigue and muscular weakness), dehydration.

Laboratory abnormalities: Very common (>=10%): hemoglobin decreased, lymphocyte count decreased, amylase increased, blood glucose increased, lipase increase, serum creatine phosphokinase increase, serum creatinine increased, alanine amino transaminase (ALT) increased, aspartate amino transaminase (AST) increased.

Interactions: Avoid concomitant use of strong CYP3A inhibitors, including but not limited to, ritonavir, saquinavir, telithromycin, ketoconazole, itraconazole, voriconazole, posaconazole and nefazodone.

Avoid concomitant use of strong CYP3A inducers, including but not limited to carbamazepine, phenobarbital, phenytoin, rifabutin, rifampin and St John’s Wort (Hypericum perforatum). If a strong CYP3A inducer must be used concomitantly with sonidegib, consideration should be given to increasing the dose of sonidegib by 200 mg increments to a maximum daily dose of 800 mg.

Monitor patients carefully for adverse drug reactions with concomitant use of substrates of CYP2B6 and CYP2C9 enzymes or BCRP transporter, especially those with a narrow therapeutic range.

Due to overlapping toxicities, patients taking Odomzo who are also taking medications known to increase the risk of muscle-related toxicity may be at increased risk of developing muscle-related adverse events. Patients should be closely monitored and dose adjustments should be considered if muscle symptoms develop.