A Single Arm, Open-Label, Multi-Centre, Phase I/II Study Evaluating the Safety and Clinical Activity of AUTO2, a CAR T Cell Treatment Targeting BCMA and TACI, in Patients with Relapsed or Refractory Multiple Myeloma

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On October 25, 2016 Onxeo S.A. (Euronext Paris, Nasdaq Copenhagen: ONXEO), an innovative company specialized in the development of orphan oncology therapeutics, reported its consolidated financials for the period ending September 30, 2016 and provided an update on major milestones achieved during the third quarter of 2016 (Press release, Onxeo, OCT 25, 2016, View Source [SID1234516029]).

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"The third quarter of 2016 was particularly eventful and productive for Onxeo. We made remarkable progress in terms of advancing our three key portfolio products as well as on the business development front. We announced results from two important preclinical studies, the first of which reinforces the rationale for developing Livatag as a potential new therapeutic option for HCC. Regarding the Livatag "ReLive" study, we are well on track to finalize the recruitment of patients in the near term, allowing the release of preliminary results in mid-2017 as planned. Data from another preclinical study confirmed the potential benefits of using AsiDNATM in combination with PARP inhibitors such as olaparib. This summer, we signed an exclusive licensing agreement with Pint Pharma for Beleodaq in South America, further expanding our product’s commercial potential. Lastly, our successful capital increase executed at the end of the third quarter has enabled us to increase our cash runway and strengthen our institutional shareholder base, including a number of US-based, specialized investors. We are well-equipped to address the opportunities expected in the coming months, as we work to deliver innovative therapeutic options that patients critically need, while creating value for our shareholders," commented Judith Greciet, CEO of Onxeo.

Continued advancement on key assets

Comprehensive preclinical and clinical work strengthening the products’ potential
Onxeo has progressed in the development of its key compound, Livatag (doxorubicin nanoformulation in Phase III trial for treatment of hepatocellular carcinoma). With more than 90% of the patients randomized as of September 30, 2016, the company is on track to deliver the preliminary results of the ReLive Phase III clinical study in mid-2017, in line with its development plan.

In an effort to expand the application of Livatag into other indications, Onxeo has also announced the first outcomes of its Livatag preclinical program, demonstrating enhanced efficacy effect in combination with immunotherapy, which validates its broader strategy for the product. Data from two in vivo studies have also confirmed the increased exposure and preferential affinity for the liver, supporting Onxeo’s current ReLive Phase III study rationale.

Onxeo has also made significant progress on Beleodaq, its pan-HDAC inhibitor already approved for PTCL (peripheral T-cell lymphoma). The company has started an initiative to develop an oral formulation of the compound, which would give a clear competitive advantage as well as expand the product’s potential application to indications for which such an oral formulation is appropriate. This development is on track, with prototypes designed and improved bioavailibity shown in an animal pharmacokinetic study.

Moreover, the company recently signed a promising new collaboration with the Royal College of Surgeons in Ireland (RCSI) for a research program on Beleodaq conjugate molecules, to improve product lifetime and stability properties, ultimately aiming to generate new patent opportunities.

Active preparation for the clinical development of first-in-class product AsiDNATM
Since the AsiDNATM acquisition, the Company has undertaken significant efforts to optimize the manufacturing process in terms of cost and duration, and is on track to manufacture its first clinical batch by the end of 2016, allowing for the initiation of a Phase I trial planned for 2017, after appropriate regulatory toxicologic assay.

The Company’s first objective is to show AsiDNATM activity when administered via the IV route, which would dramatically expand the potential of this compound. In parallel, preclinical research demonstrating the synergistic effect of Onxeo’s signal-interfering DNA product candidate in combination with various PARP (PolyADP-Ribose Polymerase) inhibitors has been published, confirming the interest of AsiDNATM compared to PARP inhibitors alone and the interest of the combination of these two DNA repair inhibitors.

Solid progress in business development and intellectual property

In the third quarter, Onxeo has strengthened its AsiDNATM intellectual property portfolio in the US with a new patent valid until 2031, confirming the innovative nature of the science behind its signal-interfering DNA product.

The company was also actively engaged in key operational and business development initiatives and achieved an important business development milestone, signing an exclusive license agreement with Pint Pharma for the commercialization of Beleodaq (belinostat) for PTCL in seven major South American countries.

Q3 revenue growth

Revenues for the third quarter of 2016 amounted to €1.23 million compared to €1.1 million in the third quarter of 2015 (+8%).

– €0.8 million of recurring revenues corresponding to product supplies to commercial partners and royalties on partners’ sales

– €0.4 million of non-recurring revenues, relating to the recognition under IFRS of upfront payments on certain licensing agreements

Over the first 9 months of the year, total revenues stood at €3.1 million, out of which €2.6 million were recurring revenues vs. €2.0 million in 2015 (+30%).

Long-term visibility reinforced with a successful €12.5 million capital increase

In early October, Onxeo successfully completed a capital increase of 5,434,783 new ordinary shares, raising gross proceeds of €12.5 million in a Private Placement. This capital increase strengthens and diversifies Onxeo’s shareholder base with the addition of prominent US-based healthcare institutional investors.

Proceeds from the capital increase, received on October 5, add to the €22.4 million consolidated cash balance at the end of September 2016, which extends Onxeo’s cash runway until Q2 2018. This capital will allow the company to pursue and accelerate the ongoing development of its pipeline assets, including the AsiDNATM and Livatag programs, as well as advance key preclinical programs, such as the combination therapy studies for AsiDNATM, Livatag, and Beleodaq.

Key near- and mid-term milestones

Livatag:
– Preclinical combination plan

– Next DSMB for Phase III trial: Q4 2016

– Preliminary Phase III trial results: expected mid-2017

AsiDNATM:
– Phase I initiation (monotherapy systemic) now expected in 2017, based on current CMC progress

Beleodaq:
– New oral formulation validated, ready to enter clinic: Q3 2017

– Preclinical combination study results: end of 2016 and onwards

– 1st-line PTCL Phase III initiation: end of 2016

On October Vertex Pharmaceuticals Incorporated (Nasdaq: VRTX) reported consolidated financial results for the quarter ended September 30, 2016 and reviewed recent progress with its approved and investigational cystic fibrosis (CF) medicines (Press release, Vertex Pharmaceuticals, OCT 25, 2016, View Source [SID1234516000]). Vertex also reiterated its financial guidance for total 2016 ORKAMBI and KALYDECO revenues and expenses. Key financial results include:

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Three Months Ended September 30,
2016 2015 % Change
(in millions, except per share and percentage data)
ORKAMBI product revenues, net $ 234 $ 131 79 %
KALYDECO product revenues, net $
176
$
166
6 %
TOTAL CF product revenues, net $
410
$
297
38 %

GAAP net loss $ (42 ) $ (95 ) (56 )%
GAAP net loss per share $ (0.17 ) $ (0.39 ) (56 )%

Non-GAAP net income (loss) $ 40 $ (32 ) N/A
Non-GAAP net income (loss) per share $ 0.16 $ (0.13 ) N/A
"Vertex continues to make significant progress with the key growth drivers for our business – increasing the number of people being treated with ORKAMBI and KALYDECO, expanding the number of people eligible for these medicines through label-expansions and developing new medicines to treat potentially all people with CF in the future," said Jeffrey Leiden, M.D., Ph.D., Chairman, President and Chief Executive Officer of Vertex. "Our progress toward treating more people with CF was marked by several important milestones in recent weeks, including the approval of ORKAMBI for children ages six to eleven in the U.S. and today’s announcement regarding the advancement of our pipeline of next-generation correctors. Importantly, we’re also continuing to generate important additional data about the long-term benefits of treating the underlying cause of CF with both ORKAMBI and KALYDECO."

Vertex today reviewed recent progress from across its CF program:

ORKAMBI

FDA approval of ORKAMBI for the treatment of children ages 6 to 11: On September 28, 2016 the U.S. Food and Drug Administration (FDA) approved ORKAMBI for the treatment of children ages 6 through 11 who have two copies of the F508del mutation. There are approximately 2,400 children ages 6 through 11 who have two copies of the F508del mutation in the U.S.

Data from Phase 3 efficacy study to support approval in children ages 6 to 11 in Europe expected by year-end: Vertex completed enrollment in a six-month Phase 3 efficacy study evaluating ORKAMBI in children ages 6 through 11 who have two copies of the F508del mutation and expects data from this study by the end of 2016. The primary endpoint of the study is the absolute change in lung clearance index. Pending data from the study, Vertex plans to submit a Marketing Authorization Application variation in the European Union in the first half of 2017. In Europe, there are approximately 3,400 children ages 6 through 11 who have two copies of the F508del mutation.

Tezacaftor (VX-661) in Combination with Ivacaftor

Enrollment complete in two Phase 3 studies of tezacaftor (VX-661); data expected in first half of 2017: Vertex has now completed enrollment in two of three ongoing Phase 3 studies of the investigational combination of tezacaftor and ivacaftor. Enrollment is complete in the Phase 3 study in people ages 12 and older who have two copies of the F508del mutation and also in the Phase 3 study in people ages 12 and older who have one F508del mutation and one residual function mutation. Data from both studies are expected in the first half of 2017. The Phase 3 study of tezacaftor in combination with ivacaftor in people with one F508del mutation and one gating mutation is expected to complete enrollment in early 2017. Vertex plans to submit a New Drug Application (NDA) to the FDA for tezacaftor in combination with ivacaftor in the second half of 2017, pending data from the Phase 3 program.

Next-Generation Correctors

Planned initiation of Phase 2 studies in CF patients: In a separate press release issued today, Vertex announced that it plans to initiate two Phase 2 studies to evaluate the next-generation correctors VX-440 and VX-152 in triple combination regimens with tezacaftor (VX-661) and ivacaftor in people with cystic fibrosis (CF). Both studies are expected to start by the end of 2016. Additional details on the design of these studies were provided today in a separate press release.

Additional next-generation correctors moving into clinical development: Vertex also reported that it plans to begin a Phase 1 study of VX-659, the company’s third next-generation corrector, by the end of 2016 and to advance a fourth next-generation corrector into clinical development in 2017. Additional details were provided today in a separate press release.

Third Quarter 2016 Financial Highlights

Revenues:

Net product revenues from ORKAMBI were $234.0 million compared to $130.8 million for the third quarter of 2015. ORKAMBI was launched in the U.S. in July 2015.
Net product revenues from KALYDECO were $175.6 million, compared to $165.9 million for the third quarter of 2015.
Expenses:

GAAP operating expenses were $435.5 million compared to $379.8 million for the third quarter of 2015. Non-GAAP operating expenses (combined non-GAAP R&D and SG&A) were $298.0 million compared to $277.7 million for the third quarter of 2015. The increases were primarily driven by increased costs related to the progression of our CF pipeline and to increased investment in global commercial support for the launch of ORKAMBI.
GAAP R&D expenses were $275.4 million compared to $246.3 million for the third quarter of 2015. Non-GAAP R&D expenses were $214.0 million compared to $201.6 million for the third quarter of 2015. The increases were primarily driven by increased investment to progress our portfolio of CF medicines.
GAAP SG&A expenses were $106.1 million compared to $99.8 million for the third quarter of 2015. Non-GAAP SG&A expenses were $84.0 million compared to $76.1 million for the third quarter of 2015. The increases were primarily driven by increased investment to support the global launch of ORKAMBI.
Net Income (Loss) Attributable to Vertex:

GAAP net loss was $(41.8) million, or $(0.17) per diluted share, compared to GAAP net loss of $(95.1) million, or $(0.39) per diluted share, for the third quarter of 2015. Non-GAAP net income was $40.1 million, or $0.16 per diluted share, compared to a non-GAAP net loss of $(31.9) million, or $(0.13) per diluted share, for the third quarter of 2015.
Cash Position:

As of September 30, 2016, Vertex had $1.13 billion in cash, cash equivalents and marketable securities compared to $1.04 billion in cash, cash equivalents and marketable securities as of December 31, 2015.
As of September 30, 2016, Vertex had $300 million outstanding from a credit agreement, which was refinanced on October 13, 2016 to lower the company’s interest expense. The $300 million outstanding under the new credit agreement matures in the fourth quarter of 2021.
2016 Financial Guidance:

Vertex today reiterated its 2016 revenue guidance for ORKAMBI and KALYDECO. The company also reiterated guidance for its 2016 combined non-GAAP R&D and SG&A expenses. The guidance is summarized below:

ORKAMBI: The company continues to expect total 2016 product revenues for ORKAMBI of $950 to $990 million.
KALYDECO: The company continues to expect total 2016 product revenues for KALYDECO of $685 to $705 million. 2016 guidance for KALYDECO currently excludes any revenues related to the potential approval of KALYDECO for people in the U.S. who have residual function mutations.
Operating Expenses (Combined Non-GAAP R&D and SG&A Expenses): Vertex continues to expect that its combined non-GAAP R&D and SG&A expenses in 2016 will be in the range of $1.18 to $1.23 billion. Vertex’s expected non-GAAP R&D and SG&A expenses exclude stock-based compensation expense and certain other expenses.
Non-GAAP Financial Measures

In this press release, Vertex’s financial results and financial guidance are provided in accordance with accounting principles generally accepted in the United States (GAAP) and using certain non-GAAP financial measures. In particular, non-GAAP financial results and guidance exclude stock-based compensation expense, revenues and expenses related to consolidated variable interest entities, costs and credits related to the relocation of the company’s corporate headquarters and hepatitis C-related revenues and costs and other adjustments. These results are provided as a complement to results provided in accordance with GAAP because management believes these non-GAAP financial measures help indicate underlying trends in the company’s business, are important in comparing current results with prior period results and provide additional information regarding the company’s financial position. Management also uses these non-GAAP financial measures to establish budgets and operational goals that are communicated internally and externally and to manage the company’s business and to evaluate its performance. The company adjusts, where appropriate, for both revenues and expenses in order to reflect the company’s operations. The company provides guidance regarding product revenues in accordance with GAAP and provides guidance regarding combined non-GAAP research and development and sales, general, and administrative expenses. The company does not provide guidance regarding GAAP research and development and sales, general, and administrative expenses because of the difficulty of estimating stock-based compensation expenses, and predicting whether or not there will be additional expense items for which adjustments are appropriate. A reconciliation of the GAAP financial results to non-GAAP financial results is included in the attached financial information.

Vertex Pharmaceuticals Incorporated
Third Quarter Results
Consolidated Statements of Operations Data
(in thousands, except per share amounts)
(unaudited)

Three Months Ended
September 30,
Nine Months Ended
September 30,
2016 2015 2016 2015
Revenues:
Product revenues, net $ 409,689 $ 302,511 $ 1,229,750 $ 593,774
Royalty revenues 3,835 5,759 12,713 17,628
Collaborative revenues 259 1,546 1,008 2,999
Total revenues 413,783 309,816 1,243,471 614,401
Costs and expenses:
Cost of product revenues (Note 1) 53,222 30,269 147,165 55,059
Royalty expenses 855 1,691 2,813 6,068
Research and development expenses 275,370 246,284 802,238 685,741
Sales, general and administrative expenses 106,055 99,772 322,921 280,026
Restructuring expenses 8 1,826 1,038 682
Total costs and expenses 435,510 379,842 1,276,175 1,027,576
Loss from operations (21,727 ) (70,026 ) (32,704 ) (413,175 )
Interest expense, net (20,140 ) (21,134 ) (60,993 ) (63,552 )
Other income (expenses), net (167 ) (1,326 ) 3,025 (5,025 )
Loss from operations before provision for income taxes (42,034 ) (92,486 ) (90,672 ) (481,752 )
Provision for income taxes 503 1,330 24,118 31,760
Net loss (42,537 ) (93,816 ) (114,790 ) (513,512 )
Loss (income) attributable to noncontrolling interest 696 (1,333 ) (33,207 ) 30,909
Net loss attributable to Vertex $ (41,841 ) $ (95,149 ) $ (147,997 ) $ (482,603 )

Amounts per share attributable to Vertex common shareholders:
Net loss:
Basic and diluted $ (0.17 ) $ (0.39 ) $ (0.61 ) $ (2.00 )
Shares used in per share calculations:
Basic and diluted 244,920 241,969 244,529 240,749

Reconciliation of GAAP to Non-GAAP Net Income (Loss)
Third Quarter Results
(in thousands, except per share amounts)
(unaudited)

Three Months Ended
September 30,
Nine Months Ended
September 30,
2016 2015 2016 2015
GAAP loss attributable to Vertex $ (41,841 ) $ (95,149 ) $ (147,997 ) $ (482,603 )
Stock-based compensation expense 61,209 65,734 178,623 186,379
Real estate restructuring costs and income (Note 2) 121 214 696 (2,186 )
HCV related revenues and costs (Note 3) (2,448 ) (7,734 ) (3,257 ) (18,207 )
Other adjustments (Notes 4 and 5) 23,090 5,007 92,460 5,631
Non-GAAP net income (loss) attributable to Vertex $ 40,131 $ (31,928 ) $ 120,525 $ (310,986 )

Amounts per diluted share attributable to Vertex common shareholders:
GAAP $ (0.17 ) $ (0.39 ) $ (0.61 ) $ (2.00 )
Non-GAAP $ 0.16 $ (0.13 ) $ 0.49 $ (1.29 )
Shares used in diluted per share calculations:
GAAP 244,920 241,969 244,529 240,749
Non-GAAP 248,009 241,969 247,433 240,749

Reconciliation of GAAP to Non-GAAP Revenues and Expenses
Third Quarter Results
(in thousands)
(unaudited)

Three Months Ended
September 30,
Nine Months Ended
September 30,
2016 2015 2016 2015
GAAP total revenues $ 413,783 $ 309,816 $ 1,243,471 $ 614,401
HCV related revenues (Note 3) (43 ) (6,415 ) (405 ) (15,378 )
Other adjustments (Note 4) (203 ) (1,105 ) (850 ) (1,379 )
Non-GAAP total revenues $ 413,537 $ 302,296 $ 1,242,216 $ 597,644

Three Months Ended
September 30,
Nine Months Ended
September 30,
2016 2015 2016 2015
GAAP cost of product revenues and royalty expenses $ 54,077 $ 31,960 $ 149,978 $ 61,127
HCV related costs (Note 3) 16 1,546 (117 ) (422 )
Non-GAAP cost of product revenues and royalty expenses $ 54,093 $ 33,506 $ 149,861 $ 60,705

GAAP research and development expenses $ 275,370 $ 246,284 $ 802,238 $ 685,741
Stock-based compensation expense (39,980 ) (44,700 ) (115,068 ) (124,550 )
HCV related costs (Note 3) 2,465 (294 ) 3,342 707
Other adjustments (Note 4) (23,889 ) 298 (36,828 ) (1,222 )
Non-GAAP research and development expenses $ 213,966 $ 201,588 $ 653,684 $ 560,676

GAAP sales, general and administrative expenses $ 106,055 $ 99,772 $ 322,921 $ 280,026
Stock-based compensation expense (21,229 ) (21,034 ) (63,555 ) (61,829 )
HCV related costs (Note 3) (76 ) (43 ) (106 ) 2,807
Other adjustments (Note 4) (758 ) (2,578 ) (2,999 ) (3,725 )
Non-GAAP sales, general and administrative expenses $ 83,992 $ 76,117 $ 256,261 $ 217,279

Combined non-GAAP R&D and SG&A expenses $ 297,958 $ 277,705 $ 909,945 $ 777,955

Three Months Ended
September 30,
Nine Months Ended
September 30,
2016 2015 2016 2015
GAAP interest expense, net and other expense, net $ (20,307 ) $ (22,460 ) $ (57,968 ) $ (68,577 )
Other adjustments (Note 4) (36 ) — 138 —
Non-GAAP interest expense, net and other expense, net $ (20,343 ) $ (22,460 ) $ (57,830 ) $ (68,577 )

GAAP provision for income taxes $ 503 $ 1,330 $ 24,118 $ 31,760
Other adjustments (Note 4) 509 (777 ) (20,063 ) (30,367 )
Non-GAAP provision for income taxes $ 1,012 $ 553 $ 4,055 $ 1,393

Condensed Consolidated Balance Sheets Data
(in thousands)
(unaudited)

September 30, 2016 December 31, 2015
Assets
Cash, cash equivalents and marketable securities $ 1,128,441 $ 1,042,462
Restricted cash and cash equivalents (VIE) (Note 5) 58,420 78,910
Accounts receivable, net 182,229 173,838
Inventories 71,799 57,207
Property and equipment, net 687,613 697,715
Intangible assets and goodwill 334,724 334,724
Other assets 141,612 113,731
Total assets $ 2,604,838 $ 2,498,587

Liabilities and Shareholders’ Equity
Other liabilities $ 434,142 $ 426,482
Deferred tax liability 133,270 110,439
Accrued restructuring expense 7,237 15,358
Deferred revenues 15,806 26,010
Capital leases 49,491 58,468
Construction financing lease obligation 468,500 473,043
Senior secured term loan 297,751 295,159
Shareholders’ equity 1,198,641 1,093,628
Total liabilities and shareholders’ equity $ 2,604,838 $ 2,498,587

Common shares outstanding 248,029 246,307
Note 1 : Cost of product revenues in the nine months ended September 30, 2016 includes the second and final $13.9 million commercial milestone that was earned by CFFT in the first quarter of 2016 related to sales of ORKAMBI.

Note 2: The company excludes restructuring expense (income) from its non-GAAP income (loss) attributable to Vertex. In the three and nine months ended September 30, 2016 and 2015, "Real estate restructuring costs and income" consisted of restructuring charges related primarily to the company’s relocation from Cambridge to Boston, Massachusetts.

Note 3: In the three and nine months ended September 30, 2016 and 2015, "HCV related revenues and costs" included net product revenues from Incivek, royalty revenues from Incivo, HCV collaborative revenues and operating costs and expenses related to HCV. The Company withdrew Incivek from the market in the United States in 2014.

Note 4: In the three months ended September 30, 2016, "Other adjustments" was primarily attributable to payments for collaborations. In the nine months ended September 30, 2016, "Other adjustments" was primarily attributable to a $58.5 million increase in the fair value of contingent milestone payments and royalties payable by Vertex to Parion due to the Phase 2 study meeting its primary safety endpoint and payments for collaborations and the acquisition of certain early stage assets.

Note 5: The company consolidates the financial statements of two of its collaborators as variable interest entities ("VIEs") as of September 30, 2016 and December 31, 2015. These VIEs are consolidated because Vertex has licensed the rights to develop the company’s collaborators’ most significant intellectual property assets. The company’s interest and obligations with respect to these VIEs’ assets and liabilities are limited to those accorded to the company in its collaboration agreements with these collaborators. Restricted cash and cash equivalents (VIE) reflects the VIEs’ cash and cash equivalents, which Vertex does not have any interest in and which will not be used to fund the collaboration. Each reporting period Vertex estimates the fair value of the contingent milestone payments and royalties payable by Vertex to these collaborators. Any increase in the fair value of these contingent milestone and royalty payments results in a decrease in net income attributable to Vertex (or an increase in net loss attributable to Vertex) on a dollar-for-dollar basis. The fair value of contingent milestone and royalty payments is evaluated each quarter and any change in the fair value is reflected in the company’s statement of operations.

INDICATION AND IMPORTANT SAFETY INFORMATION FOR KALYDECO (ivacaftor)

KALYDECO (ivacaftor) is a prescription medicine used for the treatment of cystic fibrosis (CF) in patients age 2 years and older who have one of the following mutations in their CF gene: G551D, G1244E, G1349D, G178R, G551S, S1251N, S1255P, S549N, S549R, or R117H. KALYDECO is not for use in people with CF due to other mutations in the CF gene. KALYDECO is not effective in patients with CF with two copies of the F508del mutation (F508del/F508del) in the CF gene. It is not known if KALYDECO is safe and effective in children under 2 years of age.

Patients should not take KALYDECO if they are taking certain medicines or herbal supplements such as: the antibiotics rifampin or rifabutin; seizure medications such as phenobarbital, carbamazepine, or phenytoin; or St. John’s wort.

Before taking KALYDECO, patients should tell their doctor if they: have liver or kidney problems; drink grapefruit juice, or eat grapefruit or Seville oranges; are pregnant or plan to become pregnant because it is not known if KALYDECO will harm an unborn baby; and are breastfeeding or planning to breastfeed because is not known if KALYDECO passes into breast milk.

KALYDECO may affect the way other medicines work, and other medicines may affect how KALYDECO works. Therefore the dose of KALYDECO may need to be adjusted when taken with certain medications. Patients should especially tell their doctor if they take antifungal medications such as ketoconazole, itraconazole, posaconazole, voriconazole, or fluconazole; or antibiotics such as telithromycin, clarithromycin, or erythromycin.

KALYDECO can cause dizziness in some people who take it. Patients should not drive a car, use machinery, or do anything that needs them to be alert until they know how KALYDECO affects them. Patients should avoid food containing grapefruit or Seville oranges while taking KALYDECO.

KALYDECO can cause serious side effects including:

High liver enzymes in the blood have been reported in patients receiving KALYDECO. The patient’s doctor will do blood tests to check their liver before starting KALYDECO, every 3 months during the first year of taking KALYDECO, and every year while taking KALYDECO. For patients who have had high liver enzymes in the past, the doctor may do blood tests to check the liver more often. Patients should call their doctor right away if they have any of the following symptoms of liver problems: pain or discomfort in the upper right stomach (abdominal) area; yellowing of their skin or the white part of their eyes; loss of appetite; nausea or vomiting; or dark, amber-colored urine.

Abnormality of the eye lens (cataract) has been noted in some children and adolescents receiving KALYDECO. The patient’s doctor should perform eye examinations prior to and during treatment with KALYDECO to look for cataracts. The most common side effects include headache; upper respiratory tract infection (common cold), which includes sore throat, nasal or sinus congestion, and runny nose; stomach (abdominal) pain; diarrhea; rash; nausea; and dizziness.

These are not all the possible side effects of KALYDECO.

Please click here to see the full Prescribing Information for KALYDECO (ivacaftor).

INDICATION AND IMPORTANT SAFETY INFORMATION FOR ORKAMBI (lumacaftor/ivacaftor) TABLETS

ORKAMBI is a prescription medicine used for the treatment of cystic fibrosis (CF) in patients age 6 years and older who have two copies of the F508del mutation (F508del/F508del) in their CFTR gene. ORKAMBI should only be used in these patients. It is not known if ORKAMBI is safe and effective in children under 6 years of age.

Patients should not take ORKAMBI if they are taking certain medicines or herbal supplements, such as: the antibiotics rifampin or rifabutin; the seizure medicines phenobarbital, carbamazepine, or phenytoin; the sedatives/anti-anxiety medicines triazolam or midazolam; the immunosuppressant medicines everolimus, sirolimus, or tacrolimus; or St. John’s wort.

Before taking ORKAMBI, patients should tell their doctor if they: have or have had liver problems; have kidney problems; have had an organ transplant; are using birth control (hormonal contraceptives, including oral, injectable, transdermal or implantable forms). Hormonal contraceptives should not be used as a method of birth control when taking ORKAMBI. Patients should tell their doctor if they are pregnant or plan to become pregnant (it is unknown if ORKAMBI will harm the unborn baby) or if they are breastfeeding or planning to breastfeed (it is unknown if ORKAMBI passes into breast milk).

ORKAMBI may affect the way other medicines work and other medicines may affect how ORKAMBI works. Therefore, the dose of ORKAMBI or other medicines may need to be adjusted when taken together. Patients should especially tell their doctor if they take: antifungal medicines such as ketoconazole, itraconazole, posaconazole, or voriconazole; or antibiotics such as telithromycin, clarithromycin, or erythromycin.

When taking ORKAMBI, patients should tell their doctor if they stop ORKAMBI for more than 1 week as the doctor may need to change the dose of ORKAMBI or other medicines the patient is taking. It is unknown if ORKAMBI causes dizziness. Patients should not drive a car, use machinery, or do anything requiring alertness until the patient knows how ORKAMBI affects them.

ORKAMBI can cause serious side effects including:

High liver enzymes in the blood, which can be a sign of liver injury, have been reported in patients receiving ORKAMBI. The patient’s doctor will do blood tests to check their liver before they start ORKAMBI, every three months during the first year of taking ORKAMBI, and annually thereafter. The patient should call the doctor right away if they have any of the following symptoms of liver problems: pain or discomfort in the upper right stomach (abdominal) area; yellowing of the skin or the white part of the eyes; loss of appetite; nausea or vomiting; dark, amber-colored urine; or confusion.

Respiratory events such as shortness of breath or chest tightness were observed in patients when starting ORKAMBI. If a patient has poor lung function, their doctor may monitor them more closely when starting ORKAMBI.

An increase in blood pressure has been seen in some patients treated with ORKAMBI. The patient’s doctor should monitor their blood pressure during treatment with ORKAMBI.

Abnormality of the eye lens (cataract) has been noted in some children and adolescents receiving ORKAMBI and ivacaftor, a component of ORKAMBI. For children and adolescents, the patient’s doctor should perform eye examinations prior to and during treatment with ORKAMBI to look for cataracts.

The most common side effects of ORKAMBI include: shortness of breath and/or chest tightness; upper respiratory tract infection (common cold), including sore throat, stuffy or runny nose; gastrointestinal symptoms including nausea, diarrhea, or gas; rash; fatigue; flu or flu-like symptoms; increase in muscle enzyme levels; and irregular, missed, or abnormal menstrual periods and heavier bleeding.

Please click here to see the full Prescribing Information for ORKAMBI.