Sandoz launches first generic pirfenidone in US for patients with idiopathic pulmonary fibrosis, growing its respiratory portfolio

• Pirfenidone is used to treat idiopathic pulmonary fibrosis (IPF),¹ a progressive disease that causes irreversible lung scarring and makes it difficult to breathe²
• Approximately 140,000 Americans live with IPF, a rare disease with no cure, and 50,000 new cases are diagnosed annually³
• Sandoz is committed to developing and providing patient access to high-quality, more affordable generic medicines, especially in areas of high unmet need

PRINCETON, N.J., May 12, 2022 /PRNewswire/ -- Sandoz, a global leader in generic and biosimilar medicines, today announced the US launch of its generic pirfenidone, the first AB-rated (fully substitutable) equivalent to Genentech's Esbriet^®*, to treat patients with idiopathic pulmonary fibrosis (IPF).¹ This prescription oral medicine is immediately available to patients via specialty pharmacies, with a $0 co-pay program for eligible patients.

IPF is a progressive rare disease with no cure, which causes irreversible lung scarring and makes it difficult to breathe. It primarily affects adults over age 50, and is more common in men.³ Approximately 140,000 Americans live with IPF. In addition to medicines that can slow the progression of scar tissue formation,³ it is recommended that patients stay active, eat well, and use oxygen therapy as prescribed.²

"Sandoz is putting patients first by expanding access to generic pirfenidone for those living with this rare disease, who will benefit from a more affordable, yet equally effective treatment," said Keren Haruvi, President, Sandoz Inc. "We developed this medicine in-house and continue to build our expertise and infrastructure to support our long-term commitment to grow our respiratory portfolio."

Sandoz sees considerable potential to increase patient access to high-quality, more affordable generic respiratory and specialty medicines, as few generic companies have demonstrated capabilities in this complex therapy area.

To learn more about Sandoz generic pirfenidone, visit www.sandoz-pirfenidone.com.

^* Esbriet^® is a registered trademark of Genentech, a member of the Roche Group.

Indication
Pirfenidone tablets are indicated for the treatment of idiopathic pulmonary fibrosis (IPF).

Important Safety Information
CONTRAINDICATIONS
None.

WARNINGS AND PRECAUTIONS
Elevated Liver Enzymes and Drug-Induced Liver Injury
Cases of drug-induced liver injury (DILI) have been observed with pirfenidone. In the postmarketing period, non-serious and serious cases of DILI, including severe liver injury with fatal outcome, have been reported. Patients treated with pirfenidone 2403 mg/day in three Phase 3 trials had a higher incidence of elevations in ALT or AST ≥3 × ULN than placebo patients (3.7% vs. 0.8%, respectively). Elevations ≥10 × ULN in ALT or AST occurred in 0.3% of patients in the pirfenidone 2403 mg/day group and in 0.2% of patients in the placebo group. Increases in ALT and AST ≥3 × ULN were reversible with dose modification or treatment discontinuation.

Conduct liver function tests (ALT, AST, and bilirubin) prior to the initiation of therapy with pirfenidone, monthly for the first 6 months, every 3 months thereafter, and as clinically indicated. Measure liver function tests promptly in patients who report symptoms that may indicate liver injury, including fatigue, anorexia, right upper abdominal discomfort, dark urine, or jaundice. Dosage modification or interruption may be necessary for liver enzyme elevations.

Photosensitivity Reaction or Rash
Patients treated with pirfenidone 2403 mg/day in the three Phase 3 studies had a higher incidence of photosensitivity reactions (9%) compared with patients treated with placebo (1%). The majority of the photosensitivity reactions occurred during the initial 6 months. Instruct patients to avoid or minimize exposure to sunlight (including sunlamps), to use a sunblock (SPF 50 or higher), and to wear clothing that protects against sun exposure. Additionally, instruct patients to avoid concomitant medications known to cause photosensitivity. Dosage reduction or discontinuation may be necessary in some cases of photosensitivity reaction or rash.

Gastrointestinal Disorders
In the clinical studies, gastrointestinal events of nausea, diarrhea, dyspepsia, vomiting, gastro-esophageal reflux disease, and abdominal pain were more frequently reported by patients in the pirfenidone treatment groups than in those taking placebo. Dosage reduction or interruption for gastrointestinal events was required in 18.5% of patients in the 2403 mg/day group, as compared to 5.8% of patients in the placebo group; 2.2% of patients in the pirfenidone 2403 mg/day group discontinued treatment due to a gastrointestinal event, as compared to 1.0% in the placebo group. The most common (>2%) gastrointestinal events that led to dosage reduction or interruption were nausea, diarrhea, vomiting, and dyspepsia. The incidence of gastrointestinal events was highest early in the course of treatment (with highest incidence occurring during the initial 3 months) and decreased over time. Dosage modifications may be necessary in some cases of gastrointestinal adverse reactions.

ADVERSE REACTIONS
The most common adverse reactions (≥10%) are nausea, rash, abdominal pain, upper respiratory tract infection, diarrhea, fatigue, headache, decreased appetite, dyspepsia, dizziness, vomiting, gastro-esophageal reflux disease, sinusitis, insomnia, weight decreased, and arthralgia.

DRUG INTERACTIONS
CYP1A2 Inhibitors
Pirfenidone is metabolized primarily (70 to 80%) via CYP1A2 with minor contributions from other CYP isoenzymes including CYP2C9, 2C19, 2D6 and 2E1.

Strong CYP1A2 Inhibitors
The concomitant administration of pirfenidone and fluvoxamine or other strong CYP1A2 inhibitors (e.g., enoxacin) is not recommended because it significantly increases exposure to pirfenidone. Use of fluvoxamine or other strong CYP1A2 inhibitors should be discontinued prior to administration of pirfenidone and avoided during pirfenidone treatment. In the event that fluvoxamine or other strong CYP1A2 inhibitors are the only drug of choice, dosage reductions are recommended. Monitor for adverse reactions and consider discontinuation of pirfenidone as needed.

Moderate CYP1A2 Inhibitors
Concomitant administration of pirfenidone and ciprofloxacin (a moderate inhibitor of CYP1A2) moderately increases exposure to pirfenidone. If ciprofloxacin at the dosage of 750 mg twice daily cannot be avoided, dosage reductions are recommended. Monitor patients closely when ciprofloxacin is used at a dosage of 250 mg or 500 mg once daily.

Concomitant CYP1A2 and other CYP Inhibitors
Agents or combinations of agents that are moderate or strong inhibitors of both CYP1A2 and one or more other CYP isoenzymes involved in the metabolism of pirfenidone (i.e., CYP2C9, 2C19, 2D6, and 2E1) should be discontinued prior to and avoided during pirfenidone treatment.

CYP1A2 Inducers
The concomitant use of pirfenidone and a CYP1A2 inducer may decrease the exposure of pirfenidone and this may lead to loss of efficacy. Therefore, discontinue use of strong CYP1A2 inducers prior to pirfenidone treatment and avoid the concomitant use of pirfenidone and a strong CYP1A2 inducer.

USE IN SPECIFIC POPULATIONS
Hepatic Impairment
Pirfenidone should be used with caution in patients with mild (Child Pugh Class A) to moderate (Child Pugh Class B) hepatic impairment. Monitor for adverse reactions and consider dosage modification or discontinuation of pirfenidone as needed.

The safety, efficacy, and pharmacokinetics of pirfenidone have not been studied in patients with severe hepatic impairment. Pirfenidone is not recommended for use in patients with severe (Child Pugh Class C) hepatic impairment.

Renal Impairment
Pirfenidone should be used with caution in patients with mild (CLcr 50 to 80 mL/min), moderate (CLcr 30 to 50 mL/min), or severe (CLcr less than 30 mL/min) renal impairment. Monitor for adverse reactions and consider dosage modification or discontinuation of pirfenidone as needed. The safety, efficacy, and pharmacokinetics of pirfenidone have not been studied in patients with end-stage renal disease requiring dialysis. Use of pirfenidone in patients with end-stage renal diseases requiring dialysis is not recommended.

Smokers
Smoking causes decreased exposure to pirfenidone, which may alter the efficacy profile of pirfenidone. Instruct patients to stop smoking prior to treatment with pirfenidone and to avoid smoking when using pirfenidone.

Please see full Prescribing Information for additional safety information.

Disclaimer
This press release contains forward-looking statements within the meaning of the United States Private Securities Litigation Reform Act of 1995. Forward-looking statements can generally be identified by words such as "potential," "can," "will," "plan," "may," "could," "would," "expect," "anticipate," "look forward," "believe," "committed," "investigational," "pipeline," "launch," or similar terms, or by express or implied discussions regarding potential marketing approvals, new indications or labeling for the investigational or approved products described in this press release, or regarding potential future revenues from such products. You should not place undue reliance on these statements. Such forward-looking statements are based on our current beliefs and expectations regarding future events, and are subject to significant known and unknown risks and uncertainties. Should one or more of these risks or uncertainties materialize, or should underlying assumptions prove incorrect, actual results may vary materially from those set forth in the forward-looking statements. There can be no guarantee that the investigational or approved products described in this press release will be submitted or approved for sale or for any additional indications or labeling in any market, or at any particular time. Neither can there be any guarantee that, if approved, such generic or biosimilar products will be approved for all indications included in the reference product's label. Nor can there be any guarantee that such products will be commercially successful in the future. In particular, our expectations regarding such products could be affected by, among other things, the uncertainties inherent in research and development, including clinical trial results and additional analysis of existing clinical data; regulatory actions or delays or government regulation generally; the particular prescribing preferences of physicians and patients; competition in general, including potential approval of additional generic or biosimilar versions of such products; global trends toward health care cost containment, including government, payor and general public pricing and reimbursement pressures and requirements for increased pricing transparency; litigation outcomes, including intellectual property disputes or other legal efforts to prevent or limit Sandoz from selling its products; general political, economic and business conditions, including the effects of and efforts to mitigate pandemic diseases such as COVID-19; safety, quality, data integrity or manufacturing issues; potential or actual data security and data privacy breaches, or disruptions of our information technology systems, and other risks and factors referred to in Novartis AG's current Form 20-F on file with the US Securities and Exchange Commission. Novartis is providing the information in this press release as of this date and does not undertake any obligation to update any forward-looking statements contained in this press release as a result of new information, future events or otherwise.

About Sandoz
Sandoz, a Novartis division, is a global leader in generic pharmaceuticals and biosimilars. Our purpose is to pioneer access for patients by developing and commercializing novel, affordable approaches that address unmet medical needs. Our ambition is to be the world's leading and most valued generics company. Our broad portfolio of high-quality medicines, covering all major therapeutic areas, accounted for 2021 sales of USD 9.6 billion.

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References

1. Pirfenidone. Prescribing information. Available at: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=7f5f7cc9-394e-4da0-87eb-84cfff9707a3. Accessed on May 6, 2022.
2. American Lung Association. Idiopathic Pulmonary Fibrosis (IPF). https://www.lung.org/lung-health-diseases/lung-disease-lookup/idiopathic-pulmonary-fibrosis#:~:text=Idiopathic%20pulmonary%20fibrosis%20(IPF)%20is,makes%20it%20difficult%20to%20breathe. Accessed on February 3, 2022.
3. Why We Need Idiopathic Pulmonary Fibrosis Research Now More Than Ever. American Lung Association. https://www.lung.org/blog/why-we-need-ipf-research. Published March 29, 2018. Accessed February 3, 2022.

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